FIELD OF THE INVENTION

The present invention relates to a microfluidic circuit, and associated devices, systems, methods, and components thereof.

BACKGROUND TO THE INVENTION

Microfluidic devices are miniaturised liquid handling systems typically embedded in small chips. Their size makes them suitable for use in biological, chemical, and clinical applications due to their low liquid volume demands, low cost, and disposability.

'Point-of-care' (POC) devices are a key application for microfluidics. In general, POC devices can reduce instrumentation complexity of measurement or diagnostics devices to transfer complex laboratory procedures into broad applications for untrained personnel outside the laboratory environment. In medicine, the ability to carry out an instantaneous test, and act on the results as fast as possible can be critical. In a triage situation, medical intervention can be delayed by minutes to hours because of the time taken to transport a patient to the hospital. In this situation, POC devices would allow a paramedic to test, a doctor to remotely diagnose a patient, and immediate care to be given. Beyond triage, POC devices also have the potential to positively influence equality in access to medical care. The typical medical care pipeline (consultation, testing, diagnosis, and treatment) often takes place over multiple appointments with a medical professional. For many low-income groups, multiple appointments with a doctor are not financially feasible, and as a result many individuals do not present for diagnosis and miss required medical care. Therefore, POC devices can allow timely access to medical treatment for low-income groups and similar groups. Accordingly, there are major societal, ethical, and commercial interests in improving POC devices or providing alternatives.

Some of the key challenges for POC devices are reducing cost, improving high- volume manufacturing capabilities, and ease of use. Capillaries is an emerging field within microfluidics in which capillary systems are connected in a circuit-like mannerto enable and/or improve functionality of a microfluidic circuit. Such systems are driven purely by capillary pressure, utilising surface tension effects that are determined by surface geometry and surface chemistry to automate or pre-set flow control within a microfluidic chip. As such they do not require peripheral elements to enable autonomous sampling and laboratory operations like mixing and analysis on chips. The use of self-driven capillary circuits appears to be one of the most promising approaches for POC diagnostic devices as they do not require electrical accessories and can be pre-programmed through their geometry. PCT (Patent Cooperation Treaty) patent application publication no. WO/2021/161229, the contents of which are hereby incorporated by reference, describes various microfluidic sealing valve designs and circuits that can be utilised to enable the design of complex circuitry with integrated logic and valving.

Determining an indication of the chemical or physical properties of a biological fluid is one potential application for POC diagnostics devices. A notable example is the rheological parameters, such as the viscosity, of a bodily fluid such as blood (sometimes referred to as "haemo-rheology"). Haemo-rheology can be used as a therapeutic management method for people with haematological disorders and circularity disorders, but also in the diagnosis and management of disease. Trauma, inflammation, and malignancy are all known to create alterations to a range of protein concentrations in blood plasma. Ultimately, the concentration of these proteins can affect the agglomeration of red-blood cells, and the viscosity as a result. Blood viscosity can also be also a useful indicator of cardiovascular disease, by providing an indication of the likelihood of a stroke, heart attack or other associated symptom. Due to this, the rheology of blood plasma can be used as a tool for monitoring disease.

Up to now, few viscosity measurement tools have proven their potential to be used in POC diagnostics. Microfluidic rheology chips, for instance, commonly require moving parts, pressure chambers, external (often mechanical) pumps, electronic measuring equipment, complicated internal sensors, or a combination of these elements. Although these systems result in a high level of precision, applicability for a wide range of liquids, and fast measurement time, they are still fundamentally advanced laboratory equipment. This places a limitation to where and how such a device will be used. While delays in laboratory times may be improved or minimized, test may only be conducted in a laboratory, and they still may not be fast or available enough to be used for some patients and situations. Additionally, other challenges such as temperature dependency of the viscosity can be difficult to address.

Thus, the challenges in creating a POC device for measuring or indicating a rheological property of a substance can be defined as any combination of one or more of: sufficiently high accuracy, cost-efficiency, temperature, or other external environmental factor independence, minimal or no external instrumentation, minimal number of operator inputs, ease of use (easy to perform steps), and ease of readability of the results (minimum information, high visibility).

A microfluidics device which has been recently proposed to address some of the abovementioned complexities is described in Y . Kang, S. Yang, Microfluid. Nanofluidics 2013, 14, 657. In this device, a sample and reference liquid enter a single channel simultaneously. After the liquids have entered, the channel divides into a fan like structure. Flowing under capillary action, at a rate proportional to their viscosity, the liquids create a speedometer-like readout for the relative material properties. This data representation is intuitive, and completely fulfills the requirements for ease of interoperability. Potential shortcomings are that this approach is strongly linked to production quality and orientation, as well as the need of a stationary flow regime and thus large volumes. Deviation in the height of the fanned section, due to roof sagging, or general manufacturing variation could cause errors in read-out as well.

SUMMARY OF THE INVENTION

Accordingly, it is an object of the present invention to provide an alternative microfluidic circuit or device, and associated systems or methods, for use in POC applications and that can address one or more of the abovementioned shortcomings of existing devices, or to at least provide the public with a useful choice.

In a first aspect the invention may broadly be said to consist of a microfluid circuit for providing a relative indication of a rheological property of at least one fluid substance, the circuit comprising : a plurality of flow transducing fluid channels, each flow transducing fluid channel configured to carry a separate flow of a corresponding fluid substance therethrough; and at least one pump connected to the plurality of the flow transducing fluid channels and configured to substantially simultaneously activate and sustain flow of each fluid substance through the associated flow transducing fluid channel by applying a substantially identical pump pressure to each of the flow transducing fluid channels during operation, such that the flow of the fluid substances within respective flow transducing fluid channels provides an indication of at least one characteristic of flow of at least one of the fluid substances, relative to corresponding characteristic(s) of flow of one or more fluid substance(s) in one or more of the other flow transducing fluid channel(s). In an embodiment, the at least one characteristic of flow comprises a flow rate of the at least one fluid substance relative to flow rate(s) of one or more fluid substance(s) in one or more of the other flow transducing fluid channel(s).

In an embodiment, the at least one characteristic of flow is indicative of at least one rheological property of the at least one fluid substance relative to the fluid substance(s) in the other flow transducing fluid channel(s).

In an embodiment, the at least one rheological property comprises viscosity.

In an embodiment, in use, the flow of the fluid substances within respective flow transducing fluid channels during a measurement period provides the indication of the at least one characteristic of flow of at least one of the fluid substances, relative to corresponding characteristic(s) of flow of one or more fluid substance(s) in one or more of the other flow transducing fluid channel(s).

In an embodiment, the indication of the at least one characteristic of flow is based on the displacement of the fluid substance along the respective flow transducing fluid channel relative to the displacement of other fluid substance(s) along the other flow transducing fluid channel(s) during the measurement period.

In an embodiment, the indication of the at least one characteristic of flow is based on a total volume of the fluid substance displaced along the respective flow transducing fluid channel relative to a total volume of other fluid substance(s) displaced along the other flow transducing fluid channel(s) during the measurement period.

In an embodiment, the measurement period is predefined.

In an embodiment, the measurement period is defined by a period of application of the substantially identical pump pressure.

In an embodiment, the at least one pump is(are) configured to substantially simultaneously activate flow of the fluid substances through the respective flow transducing fluid channels.

In an embodiment, the at least one pump is(are) also configured to substantially simultaneously terminate flow of the fluid substances through the respective flow transducing fluid channels. In an embodiment, a common pump is connected to the plurality of flow transducing fluid channels to apply a common pump pressure to the flow transducing fluid channels during operation.

In an embodiment, during operation, the pump is configured to activate and sustain flow of a common working fluid through the flow transducing fluid channels to apply the common pump pressure.

In an embodiment, the pump is a passive pump.

In an embodiment, the pump is a capillary pump configured to generate flow of the working fluid via capillary self-action.

In an embodiment, the capillary pump comprises a flow resistance fluids path connected downstream of the flow transducing fluid channels for generating flow of the working fluid via capillary self-action from the flow transducing fluid channels through the flow resistance path.

In an embodiment, the flow resistance fluids path of the capillary pump is connected to a void or release chamber downstream of the connection with the flow transducing fluid channels.

In an embodiment, the circuit further comprises a pump activation device or subcircuit.

In an embodiment, the pump activation sub-circuit or device comprises a microfluidics sub-circuit configured to activate flow of the working fluid through the flow resistance fluids path of the capillary pump.

In an embodiment, the microfluidic pump activation sub-circuit comprises a pump connection valve fluidly connected downstream of the flow transducing fluid channels, and fluidly connected at an outlet to an inlet of the pump for connecting the flow transducing fluid channels to the pump.

In an embodiment, the microfluidic pump activation sub-circuit further comprises a trigger flow transducing fluid channel connected to a trigger fluid inlet of the pump connection valve, the trigger flow transducing fluid channel configured to receive a trigger fluid and to direct flow into the pump connection valve for activation of the pump. In an embodiment, the trigger flow transducing fluid channel is connected to a trigger fluid intake.

In an embodiment, the trigger flow transducing fluid channel is connected to a working fluid intake.

In an embodiment, the pump connection valve is configured to simultaneously activate flow of fluid from the flow transducing fluid channels and direct flow into an inlet of the pump when a trigger fluid is received at an inlet of the pump connection valve.

In an embodiment, the pump connection valve comprises a trigger valve connection between the pump connection valve and each flow transducing fluid channel to prevent flow of fluid from the flow transducing fluid channels until a flow of fluid is received through an inlet of the pump connection valve.

In an embodiment, the microfluidic pump activation sub-circuit further comprises at least one sealing valve configured to isolate flow of fluid from the trigger flow transducing fluid channel to the pump connection valve when trigger fluid flows through or adjacent the pump connection valve inlet and/or when the pump is activated.

In an embodiment, a sealing transistor valve is connected to either side of the trigger channel, each having a transistor trigger channel connected to the pump trigger channel at or adjacent the pump connection valve inlet.

In an embodiment, the pump connection valve comprises a main channel to which the flow transducing fluid channels and pump connection valve inlet are connected, and wherein the main channel increases in cross-sectional area downstream of the pump connection valve inlet to reduce the flow rate of fluid into the pump connection valve.

In an embodiment, a cross-sectional area of the main channel gradually increases.

In an embodiment, the main channel of the pump connection valve comprises a substantially constant cross-section area downstream of the increased cross- sectional area.

In an embodiment, a working fluid intake fluidly connected upstream of each of the flow transducing fluid channels for filling each of the flow transducing fluid channels with a volume of the working fluid prior to the pump activating flow through the channels.

In an embodiment, the circuit is configured to hold the working fluid within the flow transducing fluid channel prior to the pump activating flow of the working fluid within the flow transducing fluid channel.

In an embodiment, the circuit further comprises a capillary valve fluidly connected between the working fluid intake and the input of each flow transducing fluid channel, each capillary valve being operable to isolate the working fluid intake from the associated flow transducing fluid channel after a working fluid received from the intake fills the flow transducing fluid channel.

In an embodiment, each capillary valve is transistor valve comprising an input channel connected to the working fluid intake, an outlet channel connected to the associated flow transducing fluid channel, and a trigger channel configured to activate fluid isolation between the input channel from the output channel when a fluid flows through the trigger channel.

In an embodiment, each trigger channel is fluidly connected downstream of the associated flow transducing fluid channel, such that when a working fluid flows through the outlet end of the flow transducing fluid channel it triggers the transistor valve to isolate the input channel from the output channel.

In an embodiment, the working fluid intake is fluidly connected to a substance intake chamber associated with each flow transducing fluid channel.

In an embodiment, the working fluid intake is connected to each substance intake chamber via a trigger valve that prevents fluid flow from the working fluid intake into the substance intake chamber during filling of the flow transducing fluid channels with the working fluid.

In an embodiment, the circuit further comprises a substance intake sub-circuit connected to each flow transducing fluid channel.

In an embodiment, each substance intake sub-circuit comprises a substance inlet and a substance chamber connected to the substance inlet, the substance chamber configured to hold a predefined volume of a fluid substance received by the substance inlet. In an embodiment, the circuit is configured to substantially prevent backflow of a working fluid from a flow transducing fluid channel into the respective substance chamber during filling of the substance chamber.

In an embodiment, each substance intake sub-circuit comprises a trigger valve connected between the substance chamber and the associated flow transducing fluid channel to isolate the flow transducing fluid channel from the substance chamber when the flow transducing fluid channel is being filled with a working fluid prior to the pump activating flow through the flow transducing fluid channel.

In an embodiment, each substance intake sub-circuit is operable to isolate a corresponding substance intake from the substance chamber after the substance chamber is filled to a predefined volume of a fluid.

In an embodiment, the substance intake sub-circuit comprises a capillary transistor valve having a trigger channel configured to activate the transistor to isolate the substance intake from the substance chamber when a fluid flows through the trigger channel.

In an embodiment, the trigger channel is connected to the sample chamber at the predefined volume.

In an embodiment, the trigger channel comprises a flow resistance fluids path.

In an embodiment, the trigger channel is connected to a trigger valve connected between the working fluid intake and the substance chamber at the predefined level.

In an embodiment, the plurality of flow transducing fluid channels are connected to one another in a parallel circuit arrangement.

In an embodiment, the plurality of flow transducing fluid channels are arranged in a parallel orientation relative to one another.

In an embodiment, the plurality of flow transducing fluid channels comprise substantially identical flow resistances for substantially identical fluids.

In an embodiment, the plurality of flow transducing fluid channels comprise substantially identical lengths. In an embodiment, the flow transducing fluid channels are configured to provide an indication of relative viscosity between the fluid substances flowing through the channels.

In an embodiment, the indication of relative viscosity is based on relative displacement of each fluid substance along the respective flow transducing fluid channel after termination of pumping.

In an embodiment, the circuit further comprises visual indicia adjacent at least one flow transducing fluid channel for providing a visual indication of fluid displacement along the channel.

In an embodiment, the circuit further comprises an image capture device configured to capture an image of the flow transducing fluid channels for processing and identification of the rheological property of the fluid substances in the plurality of channels.

In an embodiment, a reagent intake is connected at an inlet of at least one flow transducing fluid channel.

In an embodiment, the circuit further comprises a measurement sub-circuit fluidly connected in series downstream of each flow transducing fluids channel.

In an embodiment, each measurement sub-circuit is fluidly connected in series between the corresponding flow transducing fluid channel and the pump.

In an embodiment, each measurement circuit comprises a substance chamber for receiving and holding a volume of a fluid substance.

In an embodiment, an outlet of each flow transducing fluids channel is fluidly connected to an inlet of the substance chamber of the corresponding measurement sub-circuit.

In an embodiment, each measurement sub-circuit comprises a flow resistance fluids path fluidly connected downstream of the corresponding flow transducing fluids channel.

In an embodiment, the flow resistance fluids path is fluidly connected to the flow transducing fluids channel via a substance chamber configured to retain a predetermined volume of a fluids substance. In an embodiment, the pump is fluidly connected downstream of the flow resistance fluids path of each measurement sub-circuit.

In an embodiment, a pump connection valve is fluidly connected between the pump and the flow resistance fluids path of each measurement sub-circuit, the pump connection valve being configured to trigger flow of a fluid through the pump and to fluidly connect the flow resistance fluids path to the pump.

In an embodiment, an outlet of the flow resistance fluids path of each measurement sub-circuit is fluidly connected to a first trigger channel of a transistor valve associated with a flow path between a working fluid intake and the corresponding series connected flow transducing fluids channel.

In an embodiment, the outlet of the flow resistance fluids path of each measurement sub-circuit is fluidly connected to a second trigger channel of a transistor valve associated with a flow path between the corresponding series connected flow transducing fluids channel and the flow resistance fluids path.

In a second aspect the invention may broadly be said to consist of a microfluidic circuit for providing a relative indication of a rheological property of at least one fluid substance, the circuit comprising : a plurality of flow transducing fluid channels, each flow transducing fluid channel configured to receive a flow of a corresponding fluid substance therethrough; and at least one pump connected to the plurality of the flow transducing fluid channels and configured to activate and sustain flow of each fluid substance through the associated flow transducing fluid channel by applying a substantially identical pump pressure to each of the flow transducing fluid channels during operation, such that the flow of the fluid substances within respective flow transducing fluid channels provides an indication of at least one rheological property of at least one of the fluid substances, relative to the rheological property or properties of one or more fluid substance(s) in one or more of the other flow transducing fluid channel(s).

In a third aspect the invention may broadly be said to consist of a microfluidic circuit for providing a relative indication of a characteristic of flow of at least one fluid substance, the circuit comprising: at least one fluid channel, each fluid channel configured to receive a flow of a corresponding fluid substance therethrough; and at least one pump connected to the flow transducing fluid channel and configured to activate and sustain flow each fluid substance through the associated flow transducing fluid channel by applying a pump pressure to each of the flow transducing fluid channels during operation, such that the flow of a fluid substance within each fluid channel provides an indication of at least one characteristic of flow of the fluid substance.

In a fourth aspect the invention may broadly be said to consist of a microfluidic device comprising any of the microfluidic circuits mentioned above.

In an embodiment, the device is a viscometer configured to indicate a relative viscosity between two fluid substances.

In a fifth aspect the invention may broadly be said to consist of a microfluidic system comprising the microfluid device mentioned above.

In an embodiment, the system further comprises an analysis device for receiving the indication of relative characteristic of flow and determining an indication of a chemical or physical property of at least one of the substances based on the indication.

In an embodiment, the analysis device comprises a sensing device configured to detect the indication of relative characteristic of flow.

In an embodiment, the sensing device is an image capture device.

In an embodiment, the system further comprises a computing device communicatively coupled to the sensing device for receiving the indication and processing the indication to determine the physical or chemical property.

In a sixth aspect the invention may broadly be said to consist of a method for indicating a characteristic of flow of at least one fluid substance relative to one or more other fluid substances, the method comprising the steps of: synchronously pumping the fluid substances through respective flow transducing fluid channels of a microfluidic circuit using a substantially identical pump pressure, and providing or obtaining an indication of the at least one characteristic of flow of the at least one fluid substance based on the flow of the fluid substances within the respective flow transducing fluid channels.

In an embodiment, the step of synchronously pumping the fluid substances through the flow transducing fluid channels comprises pumping via a pump common to the plurality of flow transducing fluid channels. In an embodiment, the step of pumping via the common pump comprises pumping a common working fluid through the flow transducing fluid channels.

In an embodiment, the method further comprises the step of prefilling the flow transducing fluid channels with the working fluid prior to pumping.

In an embodiment, the method further comprises isolating flow of the working fluid from a working fluid inlet of each flow transducing fluid channel after the flow transducing fluid channels are filled with the working fluid.

In an embodiment, isolation of the working fluid inlet from each flow transducing fluid channel is performed by triggering a capillary valve associated with each flow transducing fluid channel.

In an embodiment, the method further comprises the step of prefilling a substance intake chamber via an inlet for each fluid substance.

In an embodiment, the method further comprises the step of isolating flow of fluid from the substance fluid inlet into the substance intake chamber after a predefined volume is filled.

In an embodiment, the predefined volumes of the substance intake chambers are substantially identical.

In an embodiment, the step of prefilling the substance intake chambers is performed after the flow transducing fluid channels are prefilled with the working fluid.

In an embodiment, the method further comprises triggering synchronous pumping after prefilling the substance intake chambers.

In an embodiment, the step of pumping is performed via a common capillary pump.

In an embodiment, the step of triggering synchronous pumping comprises opening a fluids channel between the flow transducing fluid channels and the common pump.

In an embodiment, the step of triggering synchronous pumping comprises providing a flow of trigger fluid through a trigger channel connected to the pump.

In an embodiment, the method further comprises the step of isolating the flow of trigger fluid from the pump when the flow transducing fluid channels are fluidly connected to the pump. In an embodiment, the multiple channels have a substantially identical flow resistance when a substantially identical fluid is flowing therethrough.

In an embodiment, the multiple channels are connected in a parallel circuit arrangement.

In an embodiment, the at least one characteristic of flow comprises a flow rate of the at least one fluid substance relative to flow rate(s) of one or more fluid substance(s) in one or more of the other flow transducing fluid channel(s).

In an embodiment, the at least one characteristic of flow is indicative of at least one rheological property of the at least one fluid substance relative to the fluid substance(s) in the other flow transducing fluid channel(s).

In an embodiment, the at least one rheological property includes viscosity.

In an embodiment, the step of synchronously pumping comprises activating flow of the fluid substances within the respective flow transducing fluid channels during a measurement period to provide the indication of the at least one characteristic of flow of at least one of the fluid substances, relative to corresponding characteristic(s) of flow of one or more fluid substance(s) in one or more of the other flow transducing fluid channel(s).

In an embodiment, the method further comprises obtaining the indication of the at least one characteristic of flow based on the displacement of the fluid substance along the respective flow transducing fluid channel relative to the displacement of other fluid substance(s) along the other flow transducing fluid channel(s) during the measurement period.

In an embodiment, the indication of the at least one characteristic of flow is based on a total volume of the fluid substance displaced along the respective flow transducing fluid channel relative to a total volume of other fluid substance(s) displaced along the other flow transducing fluid channel(s) during the measurement period.

In an embodiment, the measurement period is predefined.

In an embodiment, the measurement period is defined by a period of application of the substantially identical pump pressure. In an embodiment, a period of application is defined substantially by a predetermined volume of a flow resistance structure of a capillary pump.

In an embodiment, the method further comprises substantially simultaneously terminating flow of the fluid substances through the respective flow transducing fluid channels prior to providing or obtaining an indication of the at least one characteristic of flow of the at least one fluid substance based on the flow of the fluid substances within the respective flow transducing fluid channels.

In an embodiment, the method further comprises providing a visual indication of at least one characteristic of flow of the at least one fluid substance based on the flow of a measurement solution through a separate measurement channel associated with each flow transducing fluid channel, wherein the flow of the measurement solution is dependent on the flow of the respective fluid substance through the respective flow transducing fluid channel.

In an embodiment, each measurement channel is fluidly connected in series between the corresponding flow transducing fluid channel and the pump.

In an embodiment, the method comprises prior to providing a visual indication of the at least one characteristic of flow, prefilling a measurement solution chamber associated with and fluidly connected to each measurement channel with the respective measurement solution.

In an embodiment, the method further comprises prior to providing a visual indication of the at least one characteristic of flow, prefilling each measurement channel with a working fluid associated with the pump.

In an embodiment, the method comprises obtaining the indication of the at least one characteristic of flow based on the displacement of the measurement solution along the respective measurement channel relative to the displacement of the measurement solution along the other measurement channel(s) during the measurement period, wherein the displacement of each measurement solution through the respective measurement channel is based on the displacement of the fluid substance through the corresponding flow transducing fluid channel during the measurement period.

In a seventh aspect the invention may broadly be said to consist of a method for indicating a rheological property of at least one fluid substance relative to one or more other fluid substances, the method comprising the steps of: synchronously pumping the fluid substances through respective flow transducing fluid channels of a microfluidic circuit using a substantially identical pump pressure, and providing or obtaining an indication of the at least one rheological property of the at least one fluid substance based on the corresponding rheological property or properties of the other flow transducing fluid channels.

In an eight aspect the invention may broadly be said to consist of a method for indicating a characteristic of flow of at least one fluid substance, the method comprising the steps of: synchronously pumping the fluid substance a respective flow transducing fluid channel of a microfluidic circuit using a pump and providing or obtaining an indication of the at least one characteristic of flow for a fluid substance.

In a ninth aspect the invention may broadly be said to consist of a microfluidic valve comprising a primary trigger channel, an inlet to the primary channel, and a plurality of secondary channels fluidly connected to the primary channel, wherein the connection between each of the plurality of secondary channels and the primary channel forms a capillary trigger valve operable to trigger fluid flow from the secondary channel into the primary channel when fluid flows through the primary channel during operation, and wherein the secondary channels are arranged such that their respective trigger valves are substantially simultaneously triggered when trigger fluid flows through the primary channel during operation.

In an embodiment, the primary channel increases in cross-sectional area downstream of the inlet to reduce the flow rate of fluid into the primary channel.

In an embodiment, a cross-sectional area of the primary channel gradually increases.

In an embodiment, the primary comprises a substantially constant cross-section area downstream of the increased cross-sectional area.

In a tenth aspect the invention may broadly be said to consist of a microfluidic circuit or device comprising the microfluidic valve of the ninth aspect.

In an embodiment, the microfluidic circuit or device further comprises a trigger channel fluidly connected to the inlet of the valve.

In an embodiment, the trigger channel is connected to a trigger fluid inlet or source. In an embodiment, the circuit or device further comprises at least one sealing valve fluidly connected to the trigger channel for fluidly sealing the fluid connection between the trigger fluid source or inlet and the inlet of the valve, when a trigger fluid flows through inlet of the valve.

The microfluidic sealing valve or sealing transistor valves mentioned above may comprise a construction as indicated by any one or more of the following embodiments.

In an embodiment, the microfluidic sealing valve comprises a primary channel and optionally a secondary channel; at least one valve channel having an inlet and an outlet, the at least one valve channel in fluid communication with the primary channel or the secondary channel, the inlet of the at least one valve channel providing a connection between the at least one valve channel and the primary channel or the secondary channel, and the connection between the inlet of the at least one valve channel and the primary channel or the secondary channel having a geometry that permits liquid in the primary channel or the secondary channel to flow into the at least one valve channel through the inlet; a void volume having a first port connecting the void volume to the primary channel, the first port having a geometry that inhibits liquid in the primary channel from flowing through the first port into the void volume such that a meniscus moved by a flow of liquid in the primary channel is restrained at the first port and the outlet of the at least one valve 5 channel providing a connection between the at least one valve channel and the void volume; wherein a flow of liquid through the primary channel or the secondary channel generates a capillary force that causes the flow of liquid to flow through the inlet into the at least one valve channel, the cross-sectional area of the first port being substantially larger than a cross sectional area of the at least one valve channel such that a capillary force generated by the flow of liquid through the at least one valve channel causes the meniscus restrained at the first port to expand from the first port into the primary channel, to inhibit flow of liquid in the primary channel past the first port.

In an embodiment, the geometry of the outlet of the at least one valve channel is configured to inhibit liquid in the at least one valve channel from flowing into the void volume.

In an embodiment, the cross-sectional area of the outlet of the at least one valve channel is equal to the cross-sectional area of the at least one valve channel. In an embodiment, an inner peripheral wall of the void volume located at or adjacent the first port is angled at about 180 degrees or more relative to an imaginary plane extending across the first port. In an embodiment, an inner peripheral wall of the void volume located at or adjacent the outlet of the at least one valve channel is angled at about 180 degrees or more relative to an imaginary plane extending across the outlet. In an embodiment, the microfluidic sealing valve according to the first aspect of the invention further comprises two or more of the valve channels.

In an embodiment, the outlets of the two or more valve channels provide a connection between the two or more valve channels and the void volume.

In an embodiment, the meniscus restrained at the first port expands from the first port into the primary channel to inhibit flow of liquid in the primary channel past the first port only upon generation of a sufficient capillary force caused when a flow of liquid is incoming in both or all of the two or more valve channels, or when a flow of liquid is incoming in one of the two or more valve channels while the other of the two or more valve channels already has liquid present therein.

In an embodiment, the microfluidic sealing valve comprises a single valve channel.

In an embodiment, an intersection of channels is located at the primary channel at or adjacent the void volume so that the expansion of the meniscus restrained at the first port into the primary channel inhibits flow of liquid in the primary channel and/or in the intersection of channels past the first port.

In an embodiment, the inlet of the at least one valve channel provides the connection between the at least one valve channel and the primary channel and is in fluid communication with the primary channel.

In an embodiment, the inlet of the at least one valve channel provides the connection between the at least one valve channel and the secondary channel and is in fluid communication with the secondary channel.

In an embodiment, a length of the at least one valve channel determines the extent to which the meniscus restrained at the first port expands from the first port into the primary channel upon generation of the capillary force by the flow of liquid through the at least one valve channel. Any one of the embodiments of any one or more of the abovementioned aspects, may be combined with any one or more other aspects or embodiments of those aspects herein described, except for embodiments that are clear alternatives to one another.

The term "comprising" as used in this specification and claims means "consisting at least in part of". When interpreting each statement in this specification and claims that includes the term "comprising", features other than that or those prefaced by the term may also be present. Related terms such as "comprise" and "comprises" are to be interpreted in the same manner.

It is intended that reference to a range of numbers disclosed herein (for example, 1 to 10) also incorporates reference to all rational numbers within that range (for example, 1, 1.1, 2, 3, 3.9, 4, 5, 6, 6.5, 7, 8, 9 and 10) and also any range of rational numbers within that range (for example, 2 to 8, 1.5 to 5.5 and 3.1 to 4.7) and, therefore, all sub-ranges of all ranges expressly disclosed herein are hereby expressly disclosed. These are only examples of what is specifically intended and all possible combinations of numerical values between the lowest value and the highest value enumerated are to be expressly stated in this application in a similar manner.

As used herein the term "and/or" means "and" or "or", or both. When used as part of a list, the term "and/or" means any combination of one or more of the items in the list, unless stated otherwise.

As used herein "(s)" following a noun means the plural and/or singular forms of the noun.

The invention consists in the foregoing and envisages constructions of which the following gives examples only.

BRIEF DESCRIPTION OF THE DRAWINGS

Preferred embodiments of the invention will be described by way of example only and with reference to the drawings, in which:

Fig. 1A is a schematic of a preferred embodiment microfluidic circuit of the invention;

Fig. IB is a schematic of a preferred embodiment intake sub-circuit of the circuit of Fig. 1A; Fig. 2 is a schematic of the operating measurement principle of the circuit of Fig. 1A;

Fig. 3 is a flow diagram showing the stages of operation of the circuit of Fig. 1A;

Fig. 4A is a schematic of a device employing the circuit of Fig 1A;

Fig. 4B is a detailed schematic view the intake sub-circuit of Fig. IB;

Fig. 4C is a detailed schematic view of a pump connection valve of the circuit of Fig. 4A;

Figs. 5A-5G show various stages of operation of the device of Fig. 4A;

Fig. 6A is a flow diagram showing the steps involved in a pump preparation phase of operation of the device of Fig. 4A;

Figs. 6B is a flow diagram showing the steps involved in a substance intake phase of operation of the device of Fig. 4A;

Fig. 6C is a flow diagram showing the steps involved in a measurement phase of operation of the device of Fig. 4A;

Fig. 7A is a schematic of capillary stop valve;

Fig. 7B is a schematic of a one-level capillary trigger valve;

Figs. 7C and 7D are schematics of a two-level capillary trigger valve;

Fig. 8A shows a schematic view of an embodiment of a microfluidic sealing valve;

Fig. 8B shows a schematic view of the microfluidic sealing valve of Figure 8A with liquid flow through a primary channel;

Fig. 8C shows a schematic view of the microfluidic sealing valve of Figure 8A with liquid flow through a primary channel being inhibited;

Fig. 8D shows an isometric view of the microfluidic sealing valve of Figure 8A;

Fig. 8E shows an isometric view of the microfluidic sealing valve of Figure 8A with liquid flow through a primary channel;

Fig. 8F shows an isometric view of the microfluidic sealing valve of Figure 8A with liquid flow through a primary channel being inhibited;

Fig. 9A shows a schematic view of an embodiment of a void volume of the microfluidic sealing valve of Figure 8A; Fig. 9B shows a schematic view of the microfluidic sealing valve of Figure 8A with its inlet provided at a primary channel;

Fig. 10A shows a schematic of a second preferred embodiment microfluidic device including separate transducing and read-out sub-circuits;

Fig. 10B shows a device of the second preferred embodiment of Fig. 10A;

Fig. IOC shows the device of Fig. 10B in the measurement phase during operation;

Fig. 11 is a graph showing reference viscosity measurements used to compare test results against for the device of Fig. 4A;

Fig. 12A is a graph showing the percentage each transducing channel was filled as a function of total channel displacement for an experiment conducted used the device of Fig. 4A;

Fig. 12B is a graph showing the length ratios of the two transducing channel measurements for an experiment conducted using the device of Fig. 4A;

Fig. 13A is a graph showing the temperature disturbance capabilities of the circuit resulting from an experiment conducted with the device of Fig. 4A;

Fig. 13B is a graph the change in reported output with differential hydrostatic pressure on the sample inlets of an experiment conducted with the device of Fig. 4A;

Fig. 14 is a schematic showing different configurations possible using the transducing sub-circuits of Fig. 1A; and

Fig 15A-C are schematics of alternative forms of capillary pumps which may be utilised in the device of Fig. 4A.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

Referring to Fig. 1A a circuit diagram of a preferred embodiment microfluidics circuit 10 of a microfluidic device of the invention is shown comprising a pair of flow transducing sub-circuits 100 and 200, each being configured to receive a corresponding fluid substance 110, 210 and with the aid of a pump 150, drive the fluid substance 110, 210 through the respective sub-circuits 100, 200 to transduce flow into an indication of at least one rheological property of at least one of the substances 110, 210 relative to the other 210, 100. The term a "rheological property" as used in this specification and claims is intended to generally mean a characteristic of flow and/or deformation of the associated fluid. The rheological property may be a flow rate and/or viscosity of the fluid, for instance. The indication of the rheological property may be utilised to determine or approximate a chemical or physical property of the respective fluid substance 110, 210, such as the concentration(s) of protein(s) in blood plasma which can in turn be used to diagnose, monitor and/or manage disease in a patient. In some embodiments, the circuit 10 may be used to indicate a rheological property of a non-Newtonian fluid. In other embodiments, the circuit 10 may be used to indicate a rheological property of a Newtonian fluid . This fluid may be a biological or bodily fluid such as blood plasma, mucus, or a Synvoial fluid, or it may be a non-biological fluid. It will be appreciated that the invention is not intended to be limited to these examples and other fluids may be tested using the circuit 10 as would be readily apparent to the skilled person. Further, the circuit 10 may be used to indicate a single rheological property, or it may be used to indicate multiple rheological properties. For instance, flow rate and viscosity may be both determinable/observable using the circuit 10. The preferred embodiment described herein is intended to provide an indication of at least a viscosity of a substance, and preferably a relative viscosity between the substance and a reference. In this embodiment the device embodying the circuit 10 may be termed a "viscometer".

The circuit 10 is configured to be portable and usable in a point-of-care (POC) setting. Such a device may sometimes be referred to as a lab-on-chip (LOC) device, where measurement or analysis of substances is transferred from a complex laboratory setting to relatively untrained personnel outside of a laboratory environment.

The circuit 10 is a microfluidic based circuit, and in the preferred embodiment a capillaric circuit utilising capillary channels and components to self-pump fluids within the circuit 10 and automate the various stages of functionality. It is preferred that the circuit 10 functions with little to no requirement for external instrumentation and minimal intervention by a user, in use. In a preferred embodiment, the circuit 10 is a passive circuit in which the flow rate of the fluid(s) within the circuit are entirely governed and encoded by the design of the microfluidics and capillary channels/ systems within the circuit. This is in contrast to an actuated microfluidic circuit which may utilise external power sources or pumps to control the flow of fluid(s) within the circuit. Various capillary components may be used, including, but not limited to flow resistors, capillary pumps, reservoirs, and trigger valves to achieve the passive functionality and desired circuit programming described herein. In addition, preferred embodiments of the invention utilise recently developed transistor and sealing valve technologies, described in the Applicant's PCT patent application publication no. WO/2021/161229, the contents of which are hereby incorporated by reference. These valves assist in the initiation and termination of various stages of operation of the circuit 10, which allow for sufficient control and improve the reliability of the measurement procedure.

The circuit 10 comprises a flow transducing sub-circuit 100 for receiving and transducing the flow of a sample substance of interest, and another similar flow transducing sub-circuit 200 for receiving and transducing a reference substance. The reference substance is pre-selected based on the intended usage or application of the circuit and has a known or pre-identified rheological property, or properties, to the user or device. In this manner, the rheological property or properties of the sample substance can be observed relative to the reference substance to provide an indication of the rheological property or properties of the sample substance, and to optionally allow for the assessment of one or more other desired chemical or physical properties of the substance of interest.

This general principle of operation is illustrated in Fig. 2, in which two transducing capillary channels 20, 30 are shown, one containing a sample substance 21 of interest and the other a reference substance 31. A displacement gauge 40 is also provided between the two transducing channels 20, 30 to provide a visual indication to a user or observer of the relative physical displacement/movement of the fluids, which in turn may indicate a relative rheological property or properties of the substances 21, 31. In this example, the two substances 21 and 31 are subjected to a substantially equal driving pressure (using a pump, such as 150 for instance) for a period herein referred to as the "measurement period" or the "measurement phase". During this period/phase, each substance 21, 31 will travel a distance along the respective channel 20, 30 that is proportional to a rheological property, such as the viscosity, of the substance 21, 31. Accordingly, the relative displacements between the two substances 21, 31 can provide an observer or user with an indication of the rheological property (e.g., viscosity) of the sample substance 21 of interest. If viscosity is the property of interest, for example, then a relatively higher displacement of one substance would indicate a relatively lower viscosity, and vice versa. From this other chemical or physical properties of the substance 21 may also be deduced, such as the concentration of certain proteins in a blood analysis application. This further analysis can be performed either directly by a user or with the assistance of additional computation. In preferred embodiments, a relative measurement is used as this may remove the dependency on environmental factors, such as temperature, which can affect absolute measurements of the flow characteristics of different substances differently. However, in some embodiments, an absolute measure of displacement may be indicated or obtained using the same principle of operation mentioned above and based on preconfigured control measures or predetermined assumptions, such as a control or measured temperature of the substance and/or environment. Accordingly, the circuits described herein may be used to indicate an absolute measure of a rheological property or properties of a substance or substances and an absolute measure of a physical or chemical property may be deduced from this measure.

In this example and in any of the embodiments described herein, although two transducing channels 20, 30 are shown, three or more channels can also be used with any number of reference or sample substances as required by the application. Fig. 14 shows such a configuration, for example. In addition, although the channels 20, 30 are shown in a parallel orientation relative to one another and with substantially equal lengths, other applications may necessitate a different geometric size and/or orientation of the channels relative to one another. The invention is not intended to exclude such alternatives as this is a feature of the invention that can be designed based on the application.

In the preferred embodiment the flow transducing sub-circuits 100, 200 comprise flow transducing channels 130, 230 as per the example of Fig. 2, with additional circuitry for assisting with the preparation of substances, and the synchronous initiation of the measurement phase. Each transducing sub-circuit 100, 200 comprises substance intake sub-circuitry 120, 220 including a substance input/intake 110, 210 for prefilling the circuit with a desired substance to be measured, and the transducing channel 130, 230 for transducing the flow of the substance from the intake circuit 120, 220. The pump 150 activates and drives the flow of the fluid substance from the intake circuit 120, 220 to the transducing channel. The subcircuits 100, 200 are configured in a parallel circuit arrangement, so that a common pump 150 may be connected to both sub-circuits to synchronise the initiation measurement phase of the sub-circuits 100, 200, and to provide an equal driving pressure to the sub-circuits 100, 200, at least during this phase. Note here that a "parallel circuit arrangement" is not intended to mean a parallel orientation of the sub-circuits, although this may still be a desired feature of some embodiments. A parallel circuit arrangement in this context is akin to the parallel configuration of elements in an electrical circuit.

Referring briefly to Fig. 3, the circuit 10 is configured to operate in accordance with a method 300 and enable the following stages of operation:

1. A "pump preparation phase" 310 in which the circuit 10 is appropriately prefilled with a working fluid in the transducing channels 130, 230 for assisting with the operation of the pump 150;

2. A "substance intake phase" 320 in which the intake circuits 120, 220 are appropriately prefilled with the fluid substances to be measured; and

3. A "measurement phase" 330 as previously described, in which flow of the fluid substances in the intake circuits 120, 220 is activated and driven by the pump 150 into the transducing channel 130, 230 to transduce the flow.

The components of the circuit 10 and a capillaric device 11 embodying the circuit 10 will now be described in further detail, with reference to these stages of operation to aid with the understanding of the purpose of each circuit component/sub-circuit. Reference is also made to Figs. 1A and IB which show the circuit diagrams of the preferred embodiment, Figs. 4A-4C which show a capillaric device 11 embodying or implementing the circuit 10 shown in the circuit diagrams, Figs. 5A-5G which show the device 11 in various stages of operation, and Figs. 6A-6C which show flow diagrams of these stages of operation. The device 11 may be a POC or LOC device, for an instance an immunoassay or other biological, or non-biological, diagnostic device. Like components have been given the same reference numerals across all figures.

Pump Preparation Phase

The pump 150 includes associated circuitry that synchronises the activation and termination of flow of fluid substances through each transducing sub-circuit 100, 200 so that the flow of each substance is transduced at the same time and for the same period (i.e., both fluid substances are simultaneously subjected to a measurement phase). In some embodiments, multiple pumps 150 may be used that may collectively provide a substantially equal driving pressure to each of the sub-circuits 100, 200 during at least a measurement phase of operation. For instance, a dedicated pump may be provided to each sub-circuit 100, 200, each pump having substantially the same driving pressure as the other pump(s), and a common pump activation valve or trigger may be connected to all pumps to trigger simultaneous activation of driving pressure. In the preferred embodiment, however, a single pump 150 is used between at least two sub-circuits 100, 200 to simplify the circuit and reduce the potential for asynchronous initiation of the measurement phase for each sub-circuit 100, 200.

In the preferred embodiment, the initiation and sustained flow of fluids through each transducing sub-circuit 100, 200 during the measurement phase is not dependent on any external devices or pumps, such as syringes or electrical pumps. Instead, initiation and sustained flow of fluids through the transducing sub-circuits 100, 200 during the measurement phase is entirely governed by a capillary pump 150 comprising a flow resistance structure and a working fluid (herein also referred to as a carrier fluid). The flow resistance structure 151 is distinct from, but fluidly connected to, the flow resistance paths of each transducing channel 130, 230. The flow resistance of flow resistance structure 151 is lower than a combined, total flow resistance of transducing sub-circuits 100 and 200, such that its effects on the flow response of the circuit 10 as a whole, during the measurement phase, is minimal or negligible. The flow resistance structure 151 thereby acts to initiate and sustain flow of flow of fluids through the channels 130, 230, but the rate of flow through the channels 130, 230 is predominantly a function of the sample's viscosity and the resistances of channels 130, 230. The pump 150 is configured to apply a substantially common pressure to the transducing channels 130, 230 such that a substantially consistent sum volume of fluid is displaced through each transducing channel (i.e., sum volume of working fluid plus substance moved through each transducing channel 130, 230 is substantially the same or similar), for a given period of operation of the pump (i.e., the measurement period).

The capillary pump 150 operates to drive flow of the fluid substances throughout the circuit 10, by pumping a working fluid through and out of the sub-circuits 100, 200. The working fluid is a separate volume of fluid to the substances whose relative rheological properties are to be measured. But it is not necessarily a different composition of fluid relative to one or more of the substance(s) (although this may be preferred). The circuit 10 is therefore configured to initially receive a working fluid and prefill certain channels, including those within transducing sub-circuits 100, 200 with the working fluid. In this specification, this stage of operation of the circuit 10 is referred to as the "pump preparation phase" - stage 310 of Fig. 3. During the pump preparation phase, the flow of working fluid through each transducing sub-circuit 100, 200 is governed by the capillaric structure of the device 11, including the flow resistance(s) of the capillary channels connected to and forming each of the transducing sub-circuits 100, 200.

After the pump preparation phase, the pump 150 may be activated to initiate the measurement phase of operation, which causes the working fluid to flow through the sub-circuits and carry with it the fluid substances for measurement. The working fluid may be water or any other suitable liquid that would be acceptable for the intended application. In a preferred embodiment, a substantially low diffusion coefficient is exhibited between the working fluid and the substances to be transduced. It is preferred that a common working fluid is used throughout the circuit.

In accordance with the above functionality, the circuit 10 therefore further comprises a working fluid intake 160 (shown in Figs. 1A and 4A) that is connected to each subcircuit 100, 200 for prefilling the sub-circuits with a working fluid of interest (step 311 of Fig. 6A). The intake 160 may be in the form of a reservoir/chamber as shown in device 11 within which a working fluid may be loaded, or it may be a connection for an alternative or external fluid source. Capillary channels 161, 261 extend from the intake 160 toward each of the sub-circuits 100, 200 so that the working fluid may automatically flow through capillary self-action along the channels to prefill the required channels of each sub-circuit 100, 200, during the pump preparation phase. This step is shown in Fig. 5A and is step 312 of Fig. 6A. The capillary channels 161, 261 are connected to further capillary branches 163, 263 and 164, 264 to deliver the working fluid to the transducing channels 130, 230 and to the intake sub-circuits 120, 220, respectively.

The circuit 10 is configured such that during the pump preparation phase, the working fluid received at intake 160, is diverted through capillary self-action, into capillary branches 163, 263 and the flow transducing channels 130, respectively, to prefill these channels with the working fluid. The circuit 10 is further configured to achieve prefilling of these channels 130, 230 prior to pump activation. A pump connection valve 170 is connected between each of the flow transducing channels 130, 230 and the capillary pump flow resistance structure. The pump connection valve 170 is operable to prevent fluid in the transducing channels 130, 230 from flowing into the pump flow resistance structure 150 during the pump preparation phase. The pump connection valve 170 is also operable to permit flow of fluid in from the transducing channels 130, 230 into the pump flow resistance structure 150 during the measurement phase. This functionality is achieved in combination with a pump trigger 180 which triggers or valves the function of the pump connection valve from inhibiting flow to permitting flow, as described in further detail below. In this embodiment, a single pump connection valve 170 is provided and is configured to connect to both the transducing channels 130, 230. Similarly, a single trigger 180 is provided in the preferred embodiment. Having a single trigger and a single pump connection valve for multiple channels assists in the synchronous timing of the initiation of the measurement phase. In other embodiments, a separate valve may be connected to each of the transducing channels 130, 230. Where there are multiple pump connection valves, multiple triggers or a single trigger may be used.

Each intake sub-circuit 120, 220 is connected to the corresponding transducing channel 130, 230 of the respective transducing sub-circuit 100, 200 via a trigger valve (only valve 125 is shown in Fig. IB and referenced in Fig. 4B, but a similar valve 225 exists for sub-circuit 220 as shown in Fig. 5B) so that the flow of fluid from the intake sub-circuit 120, 220 to the transducing channel 130, 230 can be controlled and permitted to flow at the appropriate phase of operation, being the measurement phase. In other words, during the pump preparation phase, where working fluid flows into the transducing channel 130, 230 of each sub-circuit 100, 200, each valve 125, 225 will prevent the flow of working fluid into the corresponding intake sub-circuit 120, 220 and allow the substance intake phase to take place without any disturbance from the working fluid. This is shown in Fig. 5B for valve 225 and sub-circuit 220. The operation of the trigger valves 125, 225 is described in further detail in the section of the specification headed "Capillary Trigger Valves".

In this manner, during the pump preparation phase, when working fluid is received via intake 160 (step 311 of Fig. 6A), it will flow through capillary channels, 161, 261 and into capillary branches 163, 263 which bypass the intake sub-circuits 120, 220, through the flow transducing channels 130, 230 and to the pump connection valve 170 (step 312 of Fig. 6A). A sealing transistor valve 140, 240 is connected to each of the capillary bypass branches 163, 263 to seal the channel and isolate the working fluid intake 160 from the flow transducing channels 130, 230 once the flow transducing channels 130, 230 have been prefilled with the working fluid. This is to prevent further working fluid from entering the channels 130, 230 during later stages of operation including the measurement phase. The operation of the sealing transistor valve is described in further detail in section "Sealing Transistor Valves" of this specification. Each sealing transistor valve 140, 240 has a main/primary fluids channel that is connected in series between the associated capillary branch 163, 263 and intake 160, and the flow transducing channel 130, 230. In an open state of the sealing transistor valve 140, 240, the main channel 143, 243 permits fluid flow and therefore a fluid connection is made between the intake 160 and the associated flow transducing channel 130, 230. In a closed state, the sealing transistor valve 140, 240 inhibits fluid flow through the main channel 143, 243 and therefore isolates the intake 160 from the associated flow transducing channel 130, 230. Each transistor valve 140, 240 includes a trigger inlet 141, 241 configured to switch the state of operation of the valve 140, 240 from the open state to the closed state. In particular, the trigger inlet 141 is connected between the main channel 143, 243 of the sealing valve 140, 240 and to a trigger channel 142, 242. When sufficient fluid flows into the trigger channel 142, 242 connected to the trigger inlet 141, 241, this will trigger the transistor valve 140, 240 to seal the main channel 143, 243 and hence will close the connection between the intake 160 and the flow transducing channel 130, 230 (step 313 of Fig. 6A). In the preferred sealing transistor valve, the main channel 143, 243 is sealed by the expansion of a meniscus/occluding bubble into the main channel 143, 243 at the interface between the trigger inlet 141, 242 and the main channel 143, 243. This operative stage is shown in Fig. 5B for valve 240.

Each trigger channel 142, 242 is a capillary channel that is connected between the trigger inlet 141, 241 of the respective sealing valve 140, 240 and to an output/downstream end 132, 232 of the respective transducing channel 130, 230 at or adjacent the connection between the transducing channel 130, 230 and the pump connection valve 170 (shown clearly in Figs. 1A and 4A). In this manner, when working fluid flows from the intake 160 through each transducing channel 130, 230 and to pump connection valve 170, it will continue to flow through the sealing valve trigger channels 142, 242 by capillary self-action to activate sealing of the fluid connections between the intake 160 and the transducing channels 130, 230. Working fluid is now held in each transducing channel 130, 230 and is restrained in this region of the circuit by action of each transistor sealing valve 140, 240 and the pump connection valve 170 which prevent further flow in either direction. The working fluid is further restrained from flowing into the sample intake sub-circuits 120, 220 even after the valve connecting the transducing channels 130, 230 to these circuits 120, 220 are opened by action of the opposing pressures of the closed sealing valves 140, 240 and closed pump connection valve 170. In the preferred embodiment, a capillary pump 150 is utilised as it reduces the complexity and likely size of the circuit 10 and its dependence on external devices. In alternative embodiments, other pumps may be used to initiate and control flow during the measurement phase. For example, manually operated or electrical pumps, or any combination of such pumps, may be utilised by the circuit 10. Preferably, such pumps are still configured to generate and sustain a substantially consistent pumping pressure and flow across multiple transducing channels 130, 230 connected in a parallel arrangement, such that a substantially consistent sum volume of fluid is displaced through each transducing channel during the measurement phase/period.

Substance Intake Phase

Each sub-circuit 100, 200 comprise an associated substance intake 110, 210, configured to receive a respective fluid substance to be analysed or to act as a reference as previously described (step 321 of Fig. 6B). The intake 110, 210 may be a reservoir/ chamber as shown in device 11, or a connection for an alternative or external source of fluid. In some embodiments, a single substance intake may be provided for multiple intake sub-circuit branches. Intakes for reagents or other modifiers may also be included in one or more branches before or after the substance intake or connected to the working fluid intake to modify these as necessary, ultimately providing a flow of a different substance into a corresponding sub-circuit 100, 200 for indicating a rheology relative to another substance.

It is preferable that each intake 110, 210 is connected to corresponding substance intake sub-circuitry 120, 220 of a respective sub-circuit 100, 200 via a capillary channel 111, 211 (Fig. 4A). This thereby enables the fluid substance to flow from the intake 110, 210 into the corresponding intake sub-circuitry 120, 220 through capillary self-action. This stage is shown in Fig. 5C and is step 322 of Fig. 6B. In the preferred embodiment, the flow of fluid through the substance intake sub-circuitry 120, 220 during the substance intake phase is entirely governed by the flow resistance(s) of the capillaric structure of the circuitry 120, 220.

In Fig. 1A, each substance intake sub-circuit 120, 220 is shown as a generic block. Referring to Figs. IB and 4B, the components of substance intake sub-circuit 120 for performing the substance intake phase will now be described. In this embodiment, intake sub-circuit 210 will have like components and will exhibit similar functionality, in use. Each substance intake sub-circuit 120, 220, comprises a substance chamber (121 shown in Figs. IBb and 4B only, and 221 shown in Figs. 5C and 5D) configured to be prefilled with a respective substance for measurement. The purpose of the intake chamber 121 is to ensure that a predefined volume of a substance is subjected to the measurement phase for accuracy of measurement. The chambers 121, 221 of the sub-circuits 100, 200 may have a same or similar volume or they may comprise of a different volume, depending on the requirements of the intended application. Each intake sub-circuit 120, 220 is configured to perform the function of receiving a substance and prefilling the substance chamber to a predefined volume without substantially mixing with any working fluid that is in the circuit 10. This stage of operation is herein referred to as the "substance intake phase" - stage 320 of Fig. 3. This stage is typically performed after the pump preparation phase.

During the substance intake phase, each intake sub-circuit 120, 220 is also configured to fluidly isolate the associated intake 110, 210 from the substance chamber once the chamber has been filled to the predefined volume (shown in Fig. 5D and step 324 of Fig. 6B). In this manner, no additional fluid substances can flow from the intake into the chamber during the measurement phase to affect the measurement results.

As shown in Figs. IB, 4B, 5C and 5D, the substance intake of each sub-circuit 120, 220 is fluidly connected to the substance chamber 121, 221 via the capillary channel 111, 211 and via a sealing transistor valve 122, 222. The sealing transistor valve 122, 222 is similar in construction to valve 140, 240 and thereby achieves a similar function of opening and closing the fluid connection between the inlet and the chamber 121, 221 upon receipt of a trigger. In the open state, a main channel 127, 227 of each valve 122, 222, connected between the inlet and the chamber 121, 221, is open and allows fluid to flow therethrough (Fig. 5C). A fluid substance received at the chamber inlet 110, 210 will therefore proceed to flow, through capillary self- action into the respective chamber 121, 221 and fill the chamber 121, 221 until a predefined volume is reached. The predefined volume may be the full volume of the chamber 121, 221 as in the preferred embodiment, or a part of the volume of the chamber 121, 221 in some embodiments, provided the trigger valve 124, 224 is connected at a desired level within the predefined volume. The trigger inlet of the valve 122, 222 of each sub-circuit is connected to a capillary channel 123, 223 connected to the chamber 121, 221 at or adjacent the predefined volume level. At or adjacent this level of the chamber 121, 221 a trigger valve 124, 224 is also fluidly connected between the chamber 121 and the working fluid intake 160, via capillary branch 164, 264 for instance. The valve 124, 224 of each sub-circuit 120, 220 is akin in operation to valve 125 in that it is configured to permit fluid flow in an open state and inhibit fluid flow in a closed state. Its operation is described in further detail under section headed "Capillary Trigger Valves" in this specification. Each valve 124, 224 is connected and configured such that working fluid at capillary branch 164, 264 is inhibited from flowing into the corresponding trigger channel 123, 223 when the chamber 121, 221 has not been filled to the predefined volume (shown in Fig. 5B). Conversely, when fluid in each chamber 121, 221 reaches the predefined level (thereby breaking the valve seal) the working fluid is permitted to flow from the working fluid intake 160 (via capillary branch 164) into the corresponding trigger channel 123, 223. This in turn causes sealing valve 122, 222 to seal the main channel 127, 227 and fluidly isolate the connection between each substance inlet 110, 210 and the corresponding chamber 121, 221 terminating the filling of the chamber at the predefined level (Fig. 5D and step 323 of Fig. 6B). The sealing valve 122 may operate to seal the main channel 127 by expanding a meniscus/occluding bubble as explained for valve 140.

Each trigger channel 123, 223 comprises a sufficient volume to generate a sufficiently sized meniscus/occluding bubble for closing the corresponding main/primary channel 127, 227 of the transistor valve 124, 224 when a fluid flows through the channel. This volume should be achieved, while maintaining a required cross-sectional area of the channel for a required capillary self-pumping pressure. Accordingly, to maintain compactness of the device 11, each channel 123, 223 is designed with a serpentinelike structure/flow path. Other methods may be employed for achieving a desired volume of each trigger channel 123, 223 while maintaining a desired level of selfpumping pressure.

A vent 126, 226 is fluidly connected to each substance chamber 121, 221 to promote capillary self-action of fluid into the chamber 121, 221.

Valve 125, 225 of each intake sub-circuit is similar to valve 124, 224 and connected between the substance chamber 121, 221 and the flow transducing channel 130, 230. This valve inhibits flow of the working fluid from the transducing channel 130 into the chamber 121 during the pump preparation phase, as previously described. It is connected at an opposing end of valve 124, 224 and at the bottom of the chamber 121 so that when the valve 125, 225 is opened (when fluid enters chamber 121, 221) fluid is permitted to flow from the chamber 121, 221 through the valve and into the transducing flow path 130, 230. This occurs during the measurement phase where fluid flow is driven by the pump 150, which is configured to draw the working fluid in the transducing channel 130, 230 away from the intake sub-circuit 120, 220, in turn pumping the fluid in the chamber 121, 221 in the same flow direction, through the valve 125, 225 and into the transducing channel 130, 230.

Note that each valve 125, 225 may be opened prior to filling of the chamber 121, 221. However, any working fluid in transducing channel 130, 230 is prevented from flowing back through the valve 125, 225 and into the chamber 121, 221 (as shown in Fig. 5C) by action of the valve 140, 240 and pump connection valve 170, 270 as previously described.

Measurement Phase

Referring to Figs. 1A, 4A, 5E-5G and 6C, as previously mentioned each sub-circuit 100, 200 comprises a capillary flow transducing channel 130, 230 that is akin in purpose to the channels 20, 30 of Fig. 2. Each capillary flow transducing channel 130, 230 may comprise a flow resistance that is preconfigured to indicate a predefined range of measures of a rheological property or properties, for a known desired fluid substance or class of substances and with a desired balance between period of measurement and accuracy of measurement/level of sensitivity. If the purpose of the circuit 10 is to transduce flow into an indication of viscosity, for instance, then a relatively large flow resistance through each of the transducing channels 130, 230 will provide a more accurate representation of viscosity of fluid flowing through the channel, but the measurement period will be longer. Conversely, a relatively low flow resistance through each of the transducing channels 130, 230 will provide a less accurate representation of viscosity, but the measurement period will be shorter. The flow resistance of each channel 130, 230 is therefore configured to achieve a desired transduction range and a desired level of accuracy/sensitivity. It is preferred that similar resistances are used in the channels 130, 230, however, in some embodiment different flow resistances may also be feasible.

The desired flow resistance in each channel may be achieved using known microfluidic techniques, such as by changing the length of the channel via serpentine/meandering capillary channels (as in meandering sections 133, 233 of channels 130, 230 of device 11) and/or by changing the cross-sectional area of the channel. In addition, the volume of the flow resistance structure of pump 150 is preconfigured based on the volume of each associate flow resistance path 133, 233 of channels 130, 230. In addition, it is noted that the flow resistance of the pump 150 should be selected based on the flow resistance in channels 130, 230 to ensure a sufficient steady flow of fluid is maintained by the pump during the measurement phase. In the preferred embodiment, the resistance of the flow resistance structure 151 of pump 150 is lower than the flow resistance of each respective channel 130, 230 and in particular of each respective flow resistance 133, 233 of the respective channel 130, 230. The flow resistance of structure 151 may be lower than approximately 50%, or less than approximately 25%, and/or greater than approximately 10% of the flow resistance of each of channels 130, 230 for instance. The flow resistance of the pump 150 may be selected to achieve desired flow and shear rates of the substances of interest, relative to the design of the transducing channels including the substrate materials and surface treatments and channel dimensions.

At an upstream end 131, 231, each transducing channel 130, 230 is connected to both the working fluid intake 160 (via bypass channel 163, 263 and sealing valve 140, 240) and to the associated substance intake sub-circuitry 120, 220 via corresponding valve 125, 225 as previously described. At a downstream end 132, 232, each transducing channel 130, 230 is connected to the pump 150 via the pump connection valve 170 previously. Fig. 4C shows the pump connection valve in detail. The pump connection valve 170 effectively connects each transducing channel 130, 230 to the pump 150 via a corresponding valve 171, 271 (shown clearly in Fig. 4C) that permits flow of fluid only when triggered. A trigger valve 180 is connected to the pump connection valve 150 to enable the triggering of each valve connection 171, 271. The trigger valve 180 is preferably a fluid trigger wherein a flow of trigger fluid through a corresponding capillary channel 181 into the pump connection valve 170 (step 331 of Fig. 6C) will cause the valve connections 171, 271 to open (step 332 of Fig. 6C). The valve connections 171, 271 may each be a trigger valve such as a two- way trigger valve for instance, described in further detail in the section headed "Capillary Trigger Valve". The valve connections 171, 271 are preferably arranged within the flow path of the trigger fluid and within the pump connection valve 170 such that they are triggered substantially simultaneously by the action of a single trigger fluid (step 332 of Fig. 6C). As previously mentioned, these valves 171, 271 could be separated however and provided with their own trigger valves in some embodiments, or they may be separated but still share a common trigger valve. The trigger valve 180 includes a trigger fluid intake 182 (shown in Figs. 1A and 4A). This may be in the form of a reservoir/chamber, or a connection for connecting to a fluid source. In some embodiments, the intake 182 may be the same or connected to the working fluid intake 160. In such an embodiment, a resistance path may be provided between the intake 160 and the pump connection valve 170 and configured such that triggering of valves 171, 271 is sufficiently delayed allowing time for the substance intake phase to be performed.

The pump connection valve 170 is self-sealing in that once the valves 171, 271 are triggered, fluid connection with the trigger source is severed. The pump connection valve 170 may seal the trigger channel 181 using one or more sealing transistor valves 183, 283 (shown in Fig. 4A) similar to valves 140 and 122 for instance. The main channel of the sealing valve fluidly connects between the trigger fluid source and the pump connection valve inlet, and the trigger inlet of the sealing transistor valve may connect to the pump connection valve 170 inlet, the trigger channel 181 at or adjacent the pump inlet for instance. In this manner, once the trigger fluid enters the pump connection valve 170 or just before this happens, the fluid from the trigger channel 181 is diverted into the trigger inlet of the sealing transistor valve which then seals the main channel and prevents further flow of fluid from the trigger fluid source to the pump connection valve 170. A pair of sealing transistor valves 183, 283 (shown in Fig. 4A) may be connected between the trigger channel and pump connection valve 170 at either side of the channel 181. The multiple valves may improve reliability of sealing, particularly in a situation where there is less space/available volume for the associated trigger channels of the sealing valve. In other embodiments a single transistor valve may be provided but with a relatively longer trigger channel to generate a sufficiently large meniscus/occluding bubble.

The pump connection valve 170 is connected at an opposing end to the trigger fluid inlet to the capillary pump 150. As shown in Fig. 4C, a main channel 175 of the pump connection valve 170 may connect to the trigger valves 171, 271, and to the pump

150 so that when the valves 171, 271 are triggered/opened initiating the "measurement phase" (stage 330 of Fig. 3), the working fluid in each transducing channel 130, 230 will combine with the flow of fluid through the main channel 175 175 and then the combined fluid will flow through the pump flow resistance structure

151 (step 333 of Fig. 6C and shown in Fig. 5F). The flow of working fluid through the pump flow resistance structure 151 generates the pumping pressure necessary to draw the substance stored in each substance chamberl21, 221 into the respective transducing channel 130, 230 (shown in Figs. 5E-5G).

Referring to Fig. 4C, in the preferred embodiment, an inlet 176 to the main channel 175 that is at or adjacent the trigger valves 171, 271, and preferably immediately downstream of the trigger valves 171, 271, consists of an increasing cross-sectional area. This may be achieved by increasing a diameter, or width and/or depth of the main channel in this section 176. A section 177 downstream of section 176 may have a substantially uniform cross-section area/diameter. Preferably the cross-sectional area is gradually increasing in section 176. This increase in cross-sectional area at the inlet of the main channel 175 reduces the capillary pressure and hence the flow rate of fluid through the pump connection valve 170, before arriving at the pump 150. Accordingly, more time is allowed for the connection valve 170 to seal the trigger inlet, ensuring that the trigger fluid is isolated from the pump inlet at the commencement of the measurement phase. The angle of the peripheral wall of section 176 is preferably less than 180 degrees relative to an imaginary plane extending across (not through) the inlet of the pump connection valve and sufficiently small so that the interface between the inlet and section 176 does not act as a stop valve, but rather just decreases the flow rate of fluid.

The working fluid from the channels 130, 230 will combine in the main channel of the pump connection valve 170 and continue to flow into the pump 150 under a single capillary pressure, toward a vent release chamber/reservoir 190 where it may be dispensed (shown in Fig. 4A). The vent release chamber/reservoir 190 promotes the flow of working fluid through the pump flow resistance structure 151. This flow of working fluid in turn gives rise to a pumping pressure being applied to the fluid in the transducing channels 130, 230 until the pressure difference between the transducing channels 130, 230 and the chamber/reservoir equalises. This will in turn terminate the measurement phase of operation of the circuit 10. The collective volume of the flow resistance structure 151 is preferably selected to match the desired amount of fluid to be drawn in each of the transducing channels 130, 230. The volume of the flow resistance structure 151 is preferably substantially equal to the collective volumes of the transducing channels and preferably slightly more to account for leakages in the circuit (e.g., V_{pump} = V_{ control, } + V_{sample, R} + V_{Leakage at 183,283}. At this stage a measurement can, be made or observed (step 334 of Fig. 6C). The working fluids in channels 130, 230 are drawn using a single and common capillary pump pressure in the measurement phase, that is defined by the flow resistance structure of the capillary pump 150. In the preferred embodiment a volume of the flow resistance path 151 of the pump 150 is designed so that two equal viscosity fluids in the intake chambers will be pulled approximately halfway through each transducing channel resistance. The path 151 is preferably a serpentine or meandering flow resistance section. It will be appreciated that this one preferred implementation and others are possible without departing from the scope of the invention.

After the measurement phase is completed, a user or a computing device may analyse the result to determine a desired property or characteristic relating to the measure. A user may utilise a visual indication of relative displacements to interpret a desired physical or chemical property or properties of the substance of interest for instance.

In the embodiment shown, the transducing channels 130, 230 are oriented and aligned parallel to one another to compare the displacement of each substance after the measurement phase. This can provide the user with an indication of the rheological property, such as viscosity, of the substance of interest relative to the reference substance (step 334 of Fig. 6C). A displacement gauge 145, 245 (shown in Fig. 4A) including visible indicia may be provided for each channel, or a common gauge provided between the channels (as in Fig. 2), to assist a user in visibly determining relative displacement between the two substances. In other implementations, a gauge may not be provided between parallel channels, or the channels may not be parallel but may extend in different directions with a displacement gauge provided along and adjacent each channel to still provide an indication of relative displacement.

In some embodiments, an image of the measurement may be taken and analysed by an image capture device (e.g., 350 of Fig. 4A) and associated computing device to provide an indication of a rheological or other physical or chemical properties of one or more of the substances loaded into the circuit 10.

For a POC measurement, the read out could be achieved using a graphic overlay which allows the result to be interpreted without computation. One option for a visual overlay would be a linear classification type scale which shows "HIGH-MEDIUM-LOW" ranges. Alternatively, a ruler/displacement gauge overlay would allow a physician or scientist to obtain a numerical value. If logarithmically labelled rules were used in the visual overlay, then a microfluidic slide ruler like effect could be used. This would allow for easy division, and a precise numerical readout without a manual calculation or computer.

Capillary channels and pump

As described, in the preferred embodiment the circuit 10 is implemented in a capillaric device or system 11 including capillary channels (various channels of circuit previously described) and a capillary pump 150. This provides the passive operation and flow of fluids during the pump preparation, measurement, and substance intake phases of operation.

The channels within the circuit 10/device 11, including the pump 150, operate based on the creation of a Laplace pressure, created by a liquid's meniscus which in turn applies the driving pressure for the fluid within the channel. The Laplace pressure exerted by a meniscus can be calculated using the Young-Laplace Equation (1) where y is the surface tension of the liquid (N/m), P_cap is the capillary pressure, and R_horizontal and R_vertical are the primary radii of the meniscus in the horizontal and vertical direction, respectively.

These radii are dependent on the height and width of the channel as well as the top, bottom, left, and right contact angles of liquid with the corresponding four microchannel walls. A contact angle smaller than 90 degrees is preferred for the left, right and bottom microchannel walls, as the capillary pressure becomes insignificant when approaching 90 degrees, and a single imperfection in the microchannel can lead to local changes in contact angle that could disrupt circuit functionality. Surfaces that have a contact angle of less than or equal to 60 degrees are more preferred for a sufficient capillary pressure for self-powered operation in the preferred embodiment. The microfluidic device 11 may be formed from any suitable substrate material to suit the application, including glass, silicon, polymers, and hybrid structures made of multiple materials. The choice of material will affect the surface wettability/contact angles of the respective capillary channels in the circuit, and accordingly should be selected based on the desired contact angle for a particular working fluid and/or test/control substances. Some materials, such as Polydimethylsiloxane (PDMS) and polymethylmethacrylate (PMMA) may have contact angles greater than 60 degrees, e.g., close to 90 degrees. Surface treatment may be desirable for such materials to obtain wettable surfaces that provide sufficient capillary pressure. One technique for rendering a capillary circuit hydrophilic is gas phase treatments. Another commonly used hydrophilization technique is vacuum based or solution-based surface grafting of silanes with hydrophilic end groups, including notably polyethylene glycol (PEG) silanes with anti-fouling properties. The substrate could additionally or alternatively be coated with a hydrophilic material.

Furthermore, the flow rate Q of a liquid in a capillary channel of the device 11 is determined by the wettability of the channel, the viscosity of the liquid, the total flow resistance, and the pressure inside and in front of the liquid, and can be expressed as:

« = (;3 < ² > where n is the viscosity of the liquid, AP the difference in pressure inside and in front of the liquid, and RF total resistance to flow of the flow path.

Accordingly, the flow rate, Q, of each fluid traversing through the transducing channels 131, 231 is inversely proportional to the viscosity of the fluid. The flow rate in turn determines a total displacement of each fluid along the respective transducing channel, during a predefined measurement period. When the transducing channels 131, 231 comprise a substantially equal flow resistance (e.g., RF), and a common pressure is applied to each fluid flowing through the transducing channel (via common capillary pump 150), the relative displacements of the two fluids along the channels 131, 231 becomes substantially dependent on the relative viscosities of the two fluids. Note, in this case, a constant pressure value does not need to be applied by the pump 150 during the measurement period to achieve the desired result of measuring relative displacement, as long as a common pressure is applied to both transducing channels/substances. The working fluid and flow resistance structure 151 of pump 150 operate such that as the measurement period progresses, although the common pressure applied to the transducing channels 130, 230 may change, the flow of respective substances (e.g., sample and control) through the channels 130, 230 remains entirely or at least predominantly governed by the common pressure and less governed by the capillary self-action of substances through the transducing channels.

The flow resistance structure 151 of the capillary pump 150 is configured as a microchannel that is of sufficient volume to accommodate the volume of liquid that needs to be displaced. Other examples of capillary pump structures that may be utilised instead of structure 151 are shown in Figs. 15A-C. The characteristic dimensions of the structures generating capillary pressure in a capillary pump can be varied by changing the density ("Posts"), shape ("Hexagons"), relative positioning, and continuity ("Tree lines") of these structures. In other embodiments, the capillary pump may comprise a piece or section of a material capable of absorbing/wicking the working fluid, such as paper.

Capillary Trigger Valves

As mentioned above, the circuit 10 comprises several capillary valves used to assist in controlling the flow of fluid for the various stages of operation including: the trigger valves 124, 125 used in intake sub-circuit 120 (and similar valves in sub-circuit 220) and the trigger valves 171, 271 used in pump connection valve 170. These valves are passive, non-mechanical valves that utilize interfacial surface tension to block or restrict flow in a channel. Capillary valves operate without moving parts. They take advantage of forces that are created by the solid-liquid interface from liquid contact with a solid surface. By inducing an abrupt change in geometry or hydrophobicity in a surface carrying the liquid via capillary action, a liquid can be stopped at a capillary valve.

Referring to Fig. 7A, a schematic of a capillary stop valve is shown to illustrate this basic principle of operation. A local change in geometry can change the contact angle of a liquid, which will change the pressure needed to push the liquid along the capillary channel. Capillary stop valves are used to stop flow in a channel using a sudden divergence of the channel cross-section. This divergence usually means a constriction in the channel followed by a sudden enlargement, or in other words an abrupt enlargement in the cross-sectional area of a capillary channel.

Referring now to Figs. 7B-7D, schematics of one-level and two-level trigger valves are shown which illustrate two different types of modifications to the capillary stop valve. These valves utilise stop valves in a primary channel of a primary liquid (liquid 1), in combination with a trigger channel carrying a second trigger liquid (liquid 2) to create a trigger condition for resuming flow of the primary liquid.

As shown in Fig. 7B, a one level trigger valve consists of two channels that join at adjacent capillary stop valves. The first primary liquid (liquid 1) can be introduced first through the corresponding channel and stopped at the primary channel stop valve. The second trigger liquid (liquid 2) can then be introduced into the second trigger channel and when it arrives at the interface between the two channels, it breaks the seal and allows both fluids to continue flowing through the third, common downstream channel. In a one level trigger valve the increase in cross-sectional area is achieved via a sudden increase in size of the channel along one dimension, and that is preferably the width dimension, w, while the depth remains consistent between the first primary liquid channel and the combined liquid channel, and between the second liquid channel and the combined liquid channel. As shown in Fig. 7C, a two-level trigger valve works under similar principles as the one-level trigger valve, except an abrupt increase in the cross-sectional area is achieved via two dimensions, the width, w, and depth, d, of the channel. In other words, there is an increase in the cross-sectional area at the intersection between the primary channel (liquid 1) and the trigger channel (liquid 2) that is achieved by a widening of the trigger channel (relative to the primary channel) but also by increasing the depth of the trigger channel relative to the primary channel). In addition, in the two-level trigger valve, the primary channel and the trigger channel are preferably oriented at approximately 90 degrees to one another (or the main axes of liquid flow in the channels are angled 90 degrees to one another).

Referring to Fig. 7D, the geometry of an outlet 61 of the primary channel 62 is configured to inhibit liquid in the primary channel 61 from passing into the trigger channel 63. More specifically, an inner peripheral wall 64 of the trigger channel 63 located at or adjacent the outlet 61 of the primary channel 62 is angled at about 180 degrees or more relative to an imaginary plane extending across the outlet, as can be seen in Figure 9A. This geometry is shown across the width, w, dimension, and a similar geometry is exhibited in the depth, d, dimension. In the preferred device shown in Fig. 4A, this angle for the width, w, dimension is >180 degrees for valves 124, 224, 125, 225, 171 and 271 to increase the reliability of the valves in the untriggered state (by increasing the respective Laplace pressure). It will be appreciated that this angle can be designed as required by the intended application.

This angle constraint ensures that a meniscus moved by a flow of liquid passing through the trigger channel 4, in the direction C, 'pins' at the imaginary plane 65 due to surface tension effects, whereas an angle less than 180 degrees may allow the capillary forces driving the liquid flow to overcome surface tension effects, causing the meniscus, and therefore the liquid, to pass through the outlet 61 into the trigger channel 63.

In the preferred embodiment, a two-level trigger valve is used for each of the valves 171 and 271 of pump connection valve 170, and for each of the valves 124 and 125 of the intake sub-circuit 120 (with similar valves being utilised in intake sub-circuit 220).

For valves 171 and 271 the transducing channels 130, 230 act as the primary liquid channels, and the main channel 175 of the pump connection valve acts as the trigger channel. Accordingly, main channel 175 preferably comprises a larger relative depth to the channels 130, 230 and an abrupt increase in size (at 180 degrees or larger as per the required holding pressure) across the width dimension of channels 130, 230.

For valves 125, 225 of transducing channels 130, 230 act as the primary liquid channels and the substance chambers 121 221 act as the trigger channels. Accordingly, the substance chambers 121, 221 comprises a larger relative depth to the channels 130, 230 and an abrupt increase in size (at 180 degrees or larger as per the required holding pressure) across the width dimension of channels 130, 230.

For valve 124, 224 the capillary channels 164, 264 acts as the primary liquid channels and the substance chambers 121, 221 acts as the trigger channel. In this valve, multiple micro-channels 164a, b, 264a, b (preferably two but this could be more) connect the capillary channels 164, 264 with the chambers 121, 221 and accordingly result in multiple micro-trigger valves 124a, b, 224a, b at the interface. Collectively, these form a single trigger valve 124, 224. The number and size of the microchannels determines the flow resistance through the trigger valve. A higher number of micro-channels lowers the flow resistance. It will be appreciated that in some embodiments only a single channel may connect the working fluid intake 160 with each chamber 121, 221 and the invention is not intended to be limited to this implementation. Similarly, a plurality of micro-channels could be utilised for each of the other trigger valves including valves 125 (and similar), 171 and 172 without departing from the scope of the invention. The substance chambers 121, 221 preferably comprises a larger relative depth to the channels 164, 264 and an abrupt increase in size (at 180 degrees or larger as per the required holding pressure) across the width dimension of channels 164, 264.

In some embodiments, one level trigger valves may be used instead of one or more of the above-mentioned valves to achieve the same or similar functionality as described herein.

Sealing Transistor Valves

The preferred embodiment of the invention utilises microfluidic sealing transistor valves as described in PCT patent application PCT/IB2021/051153, including valves 140, 240, 185, 285 and 122 (with a similar valve being incorporated in sub-circuit 220). The following description outlines the construction and functionality of this type of valve in more detail with reference to two different valve embodiments. Any one of these embodiments may be incorporated in the circuit 10 as would be readily apparent to the skilled artisan, to achieve the desired functionality. The phrase "sealing transistor valve", "sealing valve" or "transistor valve", which may be used interchangeably in this specification and claims, are each intended to mean a valve that seals a main fluid channel based on the flow of a trigger fluid through a secondary trigger channel of the valve.

An embodiment of a microfluidic sealing valve 1, as shown in Figures 8A-8F, 9A comprises a main channel 2 (akin to the main channels 143, 243 of valves 140, 240 and main channel 127 of valve 122 for instance) and a trigger channel 4 (akin to trigger channels 142, 242 of valves 140, 240 and trigger channel 123 of valve 122 for instance) having an inlet and an outlet 6. The trigger channel 4 allows for fluid 30 communication between the trigger channel 4 and the main channel 2, via the inlet of the trigger channel 4 that provides a connection therebetween.

The inlet of the trigger channel 4 provides a connection between the trigger channel 4 and the main channel 2. Further, the outlet 6 of the trigger channel 4 provides a connection between the trigger channel 4 and the main channel 2 through a void volume 7. The void volume 7 therefore facilitates that connection between the trigger channel 4 and the main channel 2 via a first port 8 that connects the void volume 7 to the main channel 2. The first port 8 has a geometry that inhibits liquid present in the main channel 2 from flowing through the first port 8 into the void volume 7. More specifically, as can be seen in Figure 9A, an inner peripheral wall 12 of the void volume 7 located at or adjacent the first port 8 is angled at about 180 degrees or more relative to an imaginary plane 13 extending across the first port 8.

This angle constraint ensures that a meniscus 9 moved by a flow of liquid passing through the main channel 2, in the direction A, 'pins' at the imaginary plane 13 due to surface tension effects, whereas an angle less than 180 degrees may allow the capillary forces driving the liquid flow to overcome surface tension effects, causing the meniscus 9, and therefore the liquid to pass through the first port 8 into the void volume 7.

Likewise, the geometry of the outlet 6 of the trigger channel 4 is configured to inhibit liquid in the trigger channel 4 from passing into the void volume 7. More specifically, an inner peripheral wall 14 of the void volume 7 located at or adjacent the outlet 6 of the trigger channel 4 is angled at about 180 degrees or more relative to an imaginary plane 15 extending across the outlet 6, as can be seen in Figure 9A.

This angle constraint ensures that a meniscus moved by a flow of liquid passing through the trigger channel 4, in the direction B, 'pins' at the imaginary plane 15 due to surface tension effects, whereas an angle less than 180 degrees may allow the capillary forces driving the liquid flow to overcome surface tension effects, causing the meniscus, and therefore the liquid, to pass through the outlet 6 into the void volume 7.

By contrast, the connection between the inlet of the trigger channel 4 and source of trigger fluid has a geometry that permits liquid in source channel to flow into the trigger channel 4 through the inlet. Therefore, the configuration of the outlet 6 into the void volume 7, as well as the configuration of the first port 8 out of the void volume 7, prevent any liquid from flowing into the void volume 7, whether that liquid is present in the main channel 2 or the trigger channel 4. Thus, a meniscus 9 moved by a flow of liquid in the main channel 2 will 'pin', or be restrained, at the first port 8, while the flow of liquid continues downstream through the main channel 2, as shown in Figures 8B and 8E. A cross-sectional area of the first port 8 is configured to be substantially larger than a cross-sectional area of the trigger channel 4. In some configurations, a cross- sectional area of the outlet 6 of the trigger channel 4 may be equal to the cross- sectional area of the trigger channel 4. As a result of the relative sizes of the cross- sectional areas of these various features, a capillary force, generated by the flow of liquid through the trigger channel 4 causes the meniscus restrained at the first port 8 to expand from the first port 8 into the main channel 2 as shown in Figures 8C and 8F.

This forms a gaseous bubble which acts to inhibit flow of liquid in the main channel 2 past the first port 8. Depending on the extent to which the gaseous bubble extends into the main channel 2, in some configurations the gaseous bubble may act to inhibit, but allow, some flow of liquid in the main channel 2 past the first port 8. In some other configurations, as in the sealing valves of the preferred embodiment, the gaseous bubble may act to completely prevent liquid in the main channel 2 from flowing past the first port 8.

In some embodiments, the length of the trigger channel 4 partly determines the volume of gas therein displaced by the capillary force generated by the flow of liquid therethrough, and thus may determine the extent to which the gaseous bubble, or meniscus, extends or expands into the primary channel. Therefore, a length of the trigger channel 4 determines the extent to which the meniscus restrained at the first port 8 expands from the first port 8 into the main channel 2 upon generation of the capillary force by the flow of liquid through the trigger channel 4. Thus, the length of the trigger channel 4 may be configured so that the microfluidic sealing valve 1 may provide a desired flow resistance through the main channel 2 upon activation thereof.

Therefore, the microfluidic sealing valve 1 acts to inhibit flow of liquid in the main channel 2 past the first port 8 when triggered by a flow of liquid through the trigger channel 4. The trigger channel source may be the main channel itself as shown in Fig. 9B (and as is the case for valves 140, 240, 183, 283) or it may be a different source (as is the case for valve 122 and the like valve in sub-circuit 220). In the former instance, when the inlet 5 of the trigger channel 4 is connected to the main channel 2, the microfluidic sealing valve 1 can be described as a 'self-sealing' valve, in that the flow of liquid through the main channel 2 which triggers its operation, is also the same flow of liquid that is inhibited as a result of its operation. However, in the latter case, for example in the microfluidic sealing valve 122 when the inlet of the trigger channel 123 is not connected to the main channel of the valve, the microfluidic sealing valve is 'non-self-sealing', as the flow of liquid through the trigger channel that triggers its operation is not necessarily the same flow of liquid in the main channel that is inhibited as a result of its operation.

Other Embodiments

As previously mentioned, other embodiments of the invention may incorporate three or more transducing sub-circuits connected in a parallel circuit configuration to allow for relative measurement of three or more fluid substances. Fig. 14 shows a schematic of this type of configuration where there may be any number of N transducing sub-circuits, connected in a parallel circuit configuration for measuring or indicating relative rheology between three or more fluid substances. For each of these parallel branches a second or an 'n' number of other transducing sub-circuit blocks, such as read-out blocks, may be connected in series within the branch. All sub-circuits may be connected to a common pump 150.

Figs. 10A-10C show an embodiment of two transducing sub-circuits connected in a series circuit configuration, including series connected sub-circuits 100A, 100B and series connected sub-circuits 200A/200B, for instance. This configuration allows for a first sub-circuit 100A, 200A in the series to transduce the flow of a fluid substance of interest as previously mentioned, with a second sub-circuit 100B, 200B in the series providing a visible read-out of the transduced flow from the first sub-circuit

IOOA, 200A. The first sub-circuit 100A, 200A may receive a volume of a fluid substance of interest for which the relative rheological property is to be measured (e.g., the sample and control fluids) at the respective substance intake chamber, and the second sub-circuit 100B, 200B in the series may receive a volume of a visible solution (such as a dyed solution) in the respective intake chamber of that sub-circuit

IOOB, 200B. In this circuit, like features to those shown the first preferred embodiment of Figs. 4A-5G are given like references with the suffix A or B, denoting the first or second sub-circuit in the series accordingly. For example, the transducing channel 133 of Figs. 4A-5G has been referenced 133A for the first subcircuit 100A and 133B for the second subcircuit 100B, in the first series of sub-circuits. The functionality of the features with similar references to those of Figs. 4A-5G (but with an added suffix) is the same as described in relation to Figs. 4A-5G. Furthermore, not all features are referenced nor is the functionality of all features described herein in relation to Figs. 10A-10C. Only the differences relative to the circuit 10 of Figs. 4A-5G will be described herein for the sake of brevity. It will be appreciated that the full functionality of the circuit and any unreferenced features will be readily understood from the description relating to Figs. 4A-5G which is hereby incorporated by reference for Figs. 10-10C.

In this embodiment, the output of each transducing channel 133A, 233A of the first sub-circuit 100A, 200A in each series, is fluidly connected to the input capillary channel 164B, 264B of the second sub-circuit 100B, 200B in the series, which in turn is fluidly connected to the input substance chamber/reservoir 121B, 221B of the second sub-circuit 100B, 200B.

A pair of trigger channels 142A, 142B and 242A, 242B are fluidly connected to the outlet of each transducing channel 133B and 233B of each second sub-circuit 100B and 200B. A first trigger channel in the pair 142A, 242A fluidly connects to a transistor valve 122A, 222A of the first sub-circuit 100A, 200A in the series, and the second trigger channel in the pair 142B, 242B fluidly connects to a transistor valve 122B, 222B of the second sub-circuit 100B, 200B in the series.

A single pump 150, as described for the embodiment of Figs. 4A-5G, fluidly connects to the parallel transducing sub-circuit branches 100A/100B and 200A/200B to substantially synchronously activate a substantially identical driving pressure for fluid along the respective transducing channels 133A, 133B, 233A, 233B. Accordingly, the pump initiation phase operates in a similar manner as for the embodiment of Figs. 4A-5G, in which a volume of working/carrier fluid is received by a working fluid intake 182, and the working/carrier fluid is carried through the capillary branches of the circuit by capillary self-action, until both transducing channels 133A,133B and 233A,233B are filled with the fluid in each sub-circuit of the series. Once, both transducing channels are filled, the transistor valves 122A, 122B and 222A, 222B are triggered by the working/carrier fluid flowing through the respective trigger channels 142A, 142B and 242A, 242B, terminating the pump initiation phase.

During the substance intake phase, a substance whose rheological property is to be compared is received by the first intake 110A, 210A in the first sub-circuit 100A, 200A of each series, and a second, different substance/solution which may be configured to provide a visual indicia (such as a dyed solution) is separately received in the second substance intake HOB, 210B of the second sub-circuit 100B, 200B in each series. The solution loaded into the second substance chambers (which may be herein referred to as a measurement solution) may be the same for both parallel sub- circuits 100B and 200B for instance and is preferably the same solution to thereby ensure a consistent visual indication of the relative rheological properties of the substances to be compared. The substance intake phase pre-loads a volume of measurement solution into each respective substance chamber, and when a predetermined volume is received, a respective transistor valve is triggered to terminate the substance intake phase, as described in relation to Figs. 4A-5G.

The measurement phase is initiated when a pump trigger fluid is received at the intake 282 and flows, through capillary action, to the pump valve 170. This initiates the flow of working/carrier fluid from the second transducing channel 133B, 233B of the second sub-circuit 100B, 200B in each series, through the pump flow resistance structure 151. This flow continues until the flow resistance structure 151 is full, stabilising the pressure differential with the rest of the circuit. As working fluid flows through the flow resistance structure and the remainder of the circuit, a volume of fluid is displaced from each substance intake chamber 121A, 221A. Upon termination of the measurement phase, the volume of fluid displaced from the substance intake chamber 121A, 221A into the corresponding transducing channel 133A, 233A corresponds to and is substantially proportional to a rheological property, e.g., viscosity, of the fluid in the chamber. This displacement causes a corresponding displacement of the measurement solution preloaded into the corresponding second chamber 121B, 221B of each series, along the associated second transducing/measurement channel 133B, 233B. The displacement along the second transducing/measurement channel is dependent on the displacement of the first substance along the first transducing channel. If a dyed solution is used as the measurement solution, for instance, a more visible readout of the relative rheological property may be achieved at the termination of the measurement phase along the second transducing/measurement channels 133B, 233B (which may be herein referred to as: measurement channels). A visual indicator may be provided along these channels as for the embodiment of Figs. 4A-4G.

A circuit of this nature can allow for a visible indication to be provided in the secondary branches 100B, 200B of the displacement of fluid in the primary branches 100A, 200A (including the substances of interest). This is useful when the substances of interest are not opaque and substantially transparent so that their displacement along the corresponding transducing channel is difficult to observe. Rather than mixing a dye or other reagent with the substance to make it visible (which can affect its rheology), a second sub-circuit 100B, 200B is provided in series with a visible liquid dye loaded in the corresponding intake chamber to give a visible readout.

It is preferred that the flow resistance of the read-out 100B, 200B and transducing resistances 100A, 200A must be set appropriately for the analyte being measured. Similarly, the pump volume should be selected appropriately based on the collective resistances of the sub-circuits. The flow resistance of each read-out path 100B, 200B is preferably substantially lower than the flow resistance of each corresponding primary transducing channel 130A, 230A. The flow resistance of each read-out path 100B, 200B is preferably significantly lower than the flow resistance of each corresponding primary branch 100A, 200A. The total flow resistance of the read-out paths 100B, 200B may be substantially the same or similar to the flow resistance of the flow resistance structure 151 of the pump 150. The flow resistances of paths 100B and 200B are preferably substantially equal. The total flow resistance of readout paths 100B, 200B and flow resistance structure 151 are preferably significantly lower and/or negligible relative to the flow resistance of each of transducing channel 130A, 230A and/or each of transducing paths 100A, 200A to thereby enhance the sensitivity of the device/circuit, in terms of measuring a rheological property or properties of one or more fluids.

For any of the circuit embodiments described herein, it is possible to manipulate measurement result biases induced by the working fluid, by introducing a substantial source resistance between the transducing resistance and the respective sample chamber, for each transducing sub-circuit. This may be more important for certain applications over others, such as for biological fluids. As an example, blood plasma has a viscosity range very close to that of water - in the range of 1.0 - 1.3 milli-Pa.s at 37°C. In this situation, the inaccuracy created by the two-fluid flow (working and sample fluid flow) would be near maximized by the closely matching rheological properties of the sample and working fluid. In this case a highly resistive source resistance and transducing channel could be used. In the series configuration of Figs, 10A-C, this may be followed up by a relatively low resistance for the read-out channels 100B, 200B.

EXPERIMENTATION AND RESULTS

Viscous Sample Testing

The functionality of microfluid circuit 10 was tested using a device/microfluidic chip similar to preferred device 11, with a range of solutions with well-controlled fluid viscosities. The following experimentation is not intended to limit the scope of the invention to a particular microfluidic circuit constructions, substrate materials or sample/control fluids and is only provided for the purposes of exemplifying some of the benefits of the invention.

The selected samples were composed of five volumetric mixes of stock 2 kDa, and 4 kDa molecular weight poly-(ethylene-glycol) (PEG) (50%, Sigma Aldrich). The concentrations tested were (2 kDa(x) - 4 kDa (1-x)) for xe{1.0, 0.75, 0.5, 0.25, 0.0}. These volumetric mixes created an almost linear viscosity distribution, spanning between that of 2 kDa and 4 kDa PEG. The control liquid was stock 2 kDa PEG solution. For reference values, the PEG mixes were measured with a conventional cone-plate rheometer (MCR 302, Anton-Paar) over a temperature range of 0 ° C - 50 o C. The full results are shown in Fig. 11.

To test the design, the device 11 was made hydrophilic by exposure to oxygen plasma and sealed against a hydrophobic PDMS cover using a spring-loaded device clamp. The liquids were pipetted into the inlets following the operational procedure already described. The uptake of liquids was filmed from above.

The results of the measurement are shown in Fig. 12A. The y-axis of Figure 12A shows the extent to which the viscous samples filled their respective transducing resistances as a percentage. Each viscous sample was tested three times. The average of the tests is presented as solid markers, and standard deviation shown by the shaded area. In addition, a linear regression is fitted and shown as the dashed line. There is a clear linear relation in these results which confirms that the device is functioning as expected. From Figure 12A, it can be observed that there is a significant variation in the total displacement between experiments with identical samples. This is caused by the variation in the sealing time of the pump connection valve 170. If the isolating cFETs 183, 283 close slowly, a portion of the pump volume will be "wasted" by pulling liquid from the trigger inlet rather than through the transducing resistances 133, 233. However, the intended function of the viscometer is to report the ratio of these results, not the absolute result. As such, the ratio of the sample bar length, Ls, to the control bar length, Lc, is shown in Figure 12B. When recording the ratio, the deviation between runs is significantly reduced. When expressed as a ratio, the maximum standard deviation recorded was less than 2%. As well as demonstrating the precision of the device, this demonstrates the ability of circuit 10 to reduce disturbances to a viscometry measurement. Despite large variation in the pumping pressure (through contact angle variation) and pumping volume (imperfect sealing of 170) the results remain consistent.

Figure 12B also shows the ratio of the sample and control's viscosity, as measured by the conventional cone-plate rheometer. Because flow in the capillaric circuits resistors is inversely proportional to viscosity, the ratio of sample-control is used to compare to cone-plate rheometers control viscosity (p_c)/sample viscosity (p_s) result.

There is an observable offset between the ratio of measurements taken using barlengths 145, 245 and the actual viscosity ratio measured using the conventional cone-plate rheometer. The origin of this offset is the contribution of the working fluid to the total hydraulic resistance of the device. Despite this offset the device 11 remains useful in providing an indication of a rheological property of one substance relative to another. In a preferred embodiment, a visual overlay (for example including displacement gauges 145, 245) is used to remove this offset through a standard calibration process (i.e., by configuring the visual overlay to match a predefined sample and control fluids to be used with the device 11).

Device sensitivity can also be improved when the source and magnitude of spurious resistances in the circuit 11 are matched to the analyte(s) of interest. This matching process consists of adjusting all channel cross-sections such that the correct volume of viscous fluids are displaced a distance which is easily discernible by the human eye, and closely related to the rheological properties of the sample.

To match a sample and control fluid to a circuit design, the source and magnitude of all hydraulic resistances in the circuit are preferably considered. The channels crosssection can then be adjusted such that flow in the measurement phase is predominantly dependent on the sample and control fluids, while also intaking the appropriate sample volumes and generating the desired range of shear-rates for fluids in the channels. Although possible to theoretically model all elements, in practice iterative design and prototyping may be a preferred and more practical approach.

The exemplary embodiment of the device 11 presented herein is designed to intake 2 PEG samples of approximately 1.3 micro-litre each. In general, the dimensions of the resistance structure 151 is not larger than the volume of a single sample chamber (1.3ul in this case). As such, viscous samples with identical properties will each have half their total volume displaced. In this manner, in the case where p_c >> p_s or p_c << p_s, the sample or control reservoirs 121, 221 are not overemptied. The cross-sectional dimensions of transducing resistances structures 133, 233 are designed in view of this volume constraint on resistance structure 151, such that the appropriate shear-rate for the sample is applied. In addition to applied shear rate, structures 133, 233 in combination with structures 121, 221 preferably comprise a dominating (preferably greater than approximately 80%, or more preferably greater than approximately 90%) hydraulic resistance to flow relative to a remainder of the capillaric circuit 11, when in the measurement phase.

In the present exemplary embodiment, the only significant source of spurious resistance is the working fluid in the transducing resistances 133, 233. The hydraulic resistance of capillary resistance structure 151, and 161, 261, 163, 263 can be considered negligible compared to that of 133/233 in the measurement phase. As such, standard first-order microfluidic resistance modelling can be used to model the evolution of the length ratio over time, r(t) using Equation 3. r(t) = Dx((p_c-p_w)/(p_s-p_w ))x(( [-p] _w 1+ ( [ Up] _w I)] 2+2(p_s-p_w )t ))/( [-Ml _w 1+ ( [ [(pl _w I)] 2+2(p_c-p_w )t ))) (3)

Where D is a constant factor representing inhomogeneities between the two fabricated resistances, t is non-dimensional time, I is the length of the transducing resistances, and pc, ps, and pw are the viscosity of the control, sample, and working fluid, respectively.

Figure 12B shows the modelled fluid flow alongside the bar-graph viscometer's experimental data. Equation 2 was evaluated with D = 1.11, I = 50 mm, pw = 1 mPa.s, pc = 35 mPa.s, t = 5 x 10-5, and 35 < ps < 115 mPa.s to reflect the cone plate rheometer measurements.

The prediction of this model closely aligns to the experimental results. In an alternative embodiment, this offset could still be further reduced by increasing the resistance of structures 121 and221.

Disturbance insensitivity

A strength of circuit 10 is its insensitivity to common disturbances forces since all external disturbance forces equally affect both transducing channels. For viscometers, and generally for rheological analytes, the most influential disturbance is the environmental temperature since viscosity is highly dependent on this influence. Other error sources for this device include variation in hydrostatic pressure at the inlets, and the effect of manufacturing variation on the result.

To assess the temperature rejection of the bar-graph type co-stream viscometer, the chip was mounted in a custom chip clamp with an integrated Peltier stage. With the chip assembly mounted in the clamp, power was applied to the Peltier modules and the temperature of the chip measured. The temperature measurement was made using a PT-100 platinum resistance thermometer (RS-Pro, Class A, PT-100, 2 x 5.0mm, 611-7788) mounted into the chips fabricated thermometer recess. This allowed the temperature to be measured as close as possible to the transducing resistances.

The chip was preheated to within ± 1 ° C of the target and controlled to stay within this range throughout. Meanwhile, the PEG samples were pre-heated in a dry bath to the same temperature. The PEG solutions were transferred to the chip inlets using a pipette immediately prior to commencing the experiment. Each solution was tested three times, and three temperatures in total were tested (45 tests total). From the measurement shown in Fig. 11 the absolute magnitude of the viscosity change is known over the temperature range examined. The absolute magnitude of the sample and controls viscosity more than halved between 20 and 40 C. Despite this, the ratio of their viscosities remained constant - as such we expect the bar-graph viscometers output to remain constant also. Fig. 13A shows that the circuit 10 does sufficiently reject temperature disturbances, and the results remain substantially consistent.

Fig. 13B shows the influence of hydrostatic pressure imbalance on the reported result. In this test, unequal volumes of liquid were added to the sample and control inlets, respectively. As the radius of the inlets are known, this created a known variation in liquid height in the inlets, and therefore in hydrostatic pressure applied to the sample. Despite Qinlet preventing any flow from the inlet after the reservoir has been filled - the occluding bubble will still transfer hydrostatic pressure. While this method is not well controlled (due to the influence of inlet meniscus) it will be sufficient to demonstrate if an influence exists. The results in Fig. 13B show that increasing hydrostatic pressure at the sample inlet may decrease the flow in the corresponding resistance. Accordingly, a same or similar volume of substance and control fluids, in use, is preferred. Device Fabrication

The capillaric devices of the abovementioned experiments were fabricated by CNC micro-milling channels into cast Poly-(Methyl-Methacrylate) PMMA sheets (4.5 mm general purpose acrylic). A Mini-Mill/GX micro milling machine with NSK-3000 Spindle was used for this purpose. The machining tools were purchased from Performance Micro Tool (Janesville, WI, USA) in diameters of 3.175 mm (SR-4-1250-S), 250 pm (250M2X750S) and 100 pm (100M2X300S) for the square heads and 200 pm (TR-2- 0080-BN) for the ball nose. The stock material was immersed in water during machining to improve the surface quality.

Three-dimensional models, and CNC control code (G-code) were prepared using computer-aided design (CAD) software for all functional units.

The machining parameters used were varied substantially depending on the structure being machined. Generally, chip-loads of approximately 8% were used for all cutters. The depth of cut was 50% tool diameter for all tools < 200 pm diameter and 10% for tools > 200 pm diameter.

After machining, the surface of the machined chip was coated with low molecular weight PMMA solution (average Mw = 996,000, 2.5% in Chlorobenzene, Sigma Aldrich, St Louis, MO, USA). Any remaining solvent was removed by drying samples at 90°C for 5 min on a hotplate. Finally, samples were plasma-treated ten times for 1 min, each time at 15 W, pulsed mode (ratio 50) using oxygen gas (3 seem; Tergeo Plasma Cleaner, Pie Scientific, Union City, CA, USA) to remove all remaining solvents.

The invention is not intended to be limited to this device fabrication example. The device 11 may be fabricated from any suitable material known in the art including glass, plastics materials, polymers, silicon, metals, and the like. Transparent materials are desired for at least the transducing sub-circuit to enable visual observation by a user. The fabrication process or technique may include any suitable method including surface micromachining, bulk micromachining, moulding, embossing, and conventional machining with micro-cutters, for instance.

Dimensions for the capillaric channels may be 50-250 pm wide channels. Depths of channels depend on their function but may be selected to be approximately 50-250 pm deep and for chambers or voids this may be 5-500 pm. Channels and reservoirs may have any cross-sectional shape as desired by the application, including annular or rectangular cross-section. Other sizes and shapes are envisaged without departing from the scope of the invention.

Newtonian vs. non-Newtonian fluids

As mentioned, the microfluidic device 10 and circuit 11 embodiments described herein may be configured for use with Newtonian or non-Newtonian sample and control fluids, and the invention finds utility in either application. As previously mentioned, to match a sample and control fluid to a circuit design, the source and magnitude of all hydraulic resistances in the circuit are preferably considered. The channels cross-section can then be adjusted such that flow in the measurement phase is predominantly dependent on the sample and control fluids, while also intaking the appropriate sample volumes and generating the desired range of shear rates for fluids in the channels. In a non-Newtonian application, for instance, a range of shear rates applied to the sample and control fluids should be predetermined and the circuit 11 sufficiently calibrated to achieve a desired flow through the transducing channels. In addition, an advanced computer processing method may be required to determine a relative rheological property or properties of the sample fluid relative to the control fluid, within a desired level of accuracy. For example, if the flow of fluids through the transducing channels 130, 230 is recorded, a computer or other processing device may analyse the flow of the fluids during the measurement phase and based on a predetermined model determine the rheological property or properties of interest. The model may be pre-stored in electronic memory associated with and/or accessible by the processing device and may comprise a predetermined full shear-stress vs viscosity curve for a specific class or composition of nonNewtonian fluid(s), for instance. Using the total displacement of each fluid and the predefined curve, a processing device can determine the relative viscosities of the fluids through the transducing channels 130, 230. If processing is not applied, a result may still be identifiable and useful based on human observation of the flow of each non-Newtonian fluid through the associated transducing channel 133, 233. However, the total displacement of each fluid along the respective transducing channel 130, 230 during the measurement phase will provide an indication of relative average viscosities in this case. For a Newtonian fluid, as the shear-stress vs. Viscosity response is a substantially constant response, the total displacement of fluids via the respective transducing channels during the measurement phase, can provide an indication of relative viscosities without requiring additional processing or analysis. The various elements including microfluidic channels, valves, reservoirs, chambers, and flow resistors may be formed separately from other elements and connected thereto, or as preferred, the circuit is formed as a single integral component.

The embodiments described herein may require adjustments to accommodate associated fluids and/or substances of various potential implementations, as would be apparent to the skilled person. The invention is not intended to be limited to any of the abovementioned examples and other applications requiring a substantially continuous and consistent delivery of a substance into a fluid are also intended to be included without departing from the scope of the invention.

While the embodiments have been described herein with relation to a flow of fluid through the various components, the term 'fluid' or 'liquid' is to be interpreted as referring to either a completely liquid material, or a mixture of a liquid material and gaseous material.

One or more of the components and functions illustrated in the figures may be rearranged and/or combined into a single component or embodied in several components without departing from the invention. Additional elements or components may also be added without departing from the scope of the invention.

The foregoing description of the invention includes preferred forms thereof. Modifications may be made thereto without departing from the scope of the invention as defined by the accompanying claims.