FLUID DELIVERY SYSTEM

BACKGROUND OF THE INVENTION

[0001] Advances in micro-miniaturization within the semiconductor industry in recent years have enabled biotechnologists to begin packing

traditionally bulky sensing tools into smaller and smaller form factors, onto so- called biochips. Often utilizing a biochip requires liquid, gas, or other substances to be deposited and removed in a controlled sequence on or near the biochip. For example, various reagents and biological samples are flowed over the biochip in a controlled sequence to prepare the biochip, perform a measurement using the biochip, and clean the biochip for a next measurement. Manually performing this sequence is slow, error prone, and cost ineffective. Additionally, the transitioning from one measurement sample to a next measurement sample has been typically inefficient due to the steps involved in cleaning, resetting, refilling, and replacing various components. It would be desirable to develop items, systems, and techniques that are more efficient, robust, and cost-effective.

SUMMARY OF THE INVENTION [0002] In one aspect, the present invention provides a delivery system or apparatus for a sensor chip. In one embodiment, the system comprises a first assembly and a second assembly. In another embodiment, the system comprises a plurality of selectable ports arranged on the first assembly. In an additional embodiment, each of the selectable ports is in communication with a separate channel. In one other embodiment, the second assembly is movable in relation to the first assembly. In one additional embodiment, the second assembly comprises a plurality of channels that are mechanically connectable to different ones of the plurality of selectable ports on the first assembly by motion of the second assembly relative to the first assembly. In another embodiment, the system further comprises a mechanical interface configured to engage a separate actuator so that relative motion of the first assembly and the second assembly is affected by the actuator. [0003] In another aspect, the system or appratus comprises a second assembly that is movable in relation to the first assembly. In one embodiment, the second assembly is movable in relation to the first assembly to simultaneously connect a first channel of the plurality of channels of the second assembly to a first port of the selectable ports of the first assembly and a second channel of the plurality of channels of the second assembly to a second port of the selectable ports of the first assembly. In another embodiment, the second assembly includes gear teeth around a rim of the second assembly. In one other embodiment, the first assembly and the second assembly are enclosed in a removable cartridge configured to engage with an instrument device.

[0004] In one other aspect, the system or apparatus comprises a second assembly of the system comprises a channel that is assigned to store different contents and/or assigned not to store certain contents. In one embodiment, the system comprises a second assembly, wherein one of the plurality of channels is assigned to not store non-aqueous content. In one other embodiment, non-aqueous content is absent from or is excluded from the channel. In another embodiment, the assignment of the channel not to store non-aqueous content minimizes cross contamination with potential aqueous content that may be stored in the one of the plurality of channels. In an additional embodiment, the system comprises a second assembly, wherein one of the plurality of channels is assigned to not store aqueous content. In one other embodiment, aqueous content is absent from or is excluded from the channel. In another embodiment, the assignment of the channel not to store aqueous content minimizes cross contamination with potential non-aqueous content that may be stored in the one of the plurality of channels. [0005] In an additional aspect, some of the plurality of selectable ports arranged on the first assembly are connected other parts of the system. In one embodiment, at least one of the plurality of selectable ports is connected to a reagent reservoir. In another embodiment, another one of the plurality of selectable ports is connected to a chamber of the sensor chip. In an additional embodiment, a first selectable port is connected to a reagent reservoir and a second selectable port is connected to a chamber of the sensor chip. [0006] In one other aspect, the first assembly of the system or apparatus of the present invention further comprises a crossover channel. In one embodiment, the first assembly comprises a crossover channel that connects together at least two of the channels of the second assembly. In another embodiment, the first assembly comprises a plurality of crossover channels.

[0007] In one aspect, some channels of the plurality of channels in the second assembly are connected to other parts of the system. In one embodiment, a first channel of the plurality of channels is configured to be connected to a pump. In another embodiment, a second channel of the plurality of channels is configured to be only connected to the pump via the first channel. In another embodiment, the plurality of channels is at least in part formed as grooves in the second assembly.

[0008] In one additional embodiment, a first channel of the plurality of channels is configured to deliver content to an input port of the sensor chip. In one other embodiment, a second channel of the plurality of channels is configured to deliver content to an output port of the sensor chip.

[0009] In one additional aspect, the present invention provides an alternative delivery system or apparatus for a sensor chip. In one embodiment, the system comprises a plurality of selectable ports arranged on a first assembly. In other embodiments, each of the selectable ports is in communication with a separate channel. In a further embodiment, the system further comprises a second assembly movable in relation to the first assembly. In another embodiment, the second assembly has a channel that is mechanically connectable to different ones of the plurality of selectable ports on the first assembly by motion of the second assembly relative to the first assembly and the second assembly includes one or more optical openings configured to indicate a position of the second assembly relative to the first assembly. In one additional embodiment, the system further comprises a mechanical interface configured to engage a separate actuator so that relative motion of the first assembly and the second assembly is affected by the actuator. [0010] In other embodiments, the position of the second assembly includes a selectable radial valve rotational position. In another embodiment, one or more optical openings are utilized to detect a reference home position of the second assembly. In a further embodiment, the optical openings have been injection molded on to the second assembly. In one embodiment, the optical openings include a hole that allows a light to pass through the second assembly. In one other embodiment, the first assembly includes an optical window that aligns with at least one of the one or more optical openings to allow a light to pass through the optical window and the at least one of the one or more optical openings. In a further embodiment, the first assembly includes a first optical window and a second optical window and a first group of one or more optical openings is only eligible to be aligned with the first optical window and a second group of one or more optical openings is only eligible to be aligned with the second optical window. In one embodiment, at least a portion of the one or more optical openings is distributed around an outer rim of the second assembly and each of the optical openings distributed around the outer rim corresponds to a different selectable valve position.

[0011] In one other aspect, the present invention provides a reagent cartridge for use with a biochip. In one embodiment, the reagent cartridge comprises a reagent reservoir. In another embodiment, the reagent reservoir includes a winding chamber. In one other embodiment, the winding chamber of the reagent reservoir is serpentine in shape. In other embodiments, at least one side of the winding chamber is thermally conductive and configured to contact a thermal source. In one other embodiment, another side of the winding chamber is less thermally conductive than the at least one side of the winding chamber that is thermally conductive. In an additional embodiment, the reagent cartridge further comprises an input port to the reagent reservoir (or an input port for each reagent reservoir). In one other embodiment, the input port is configured to accept a pipette. In yet another embodiment, the reagent cartridge further comprises an output port of the reagent reservoir configured to provide a reagent in the reagent reservoir to a biochip. In one other embodiment, the output port of the reagent reservoir is one of a plurality of selectable ports of a radial valve included in the reservoir cartridge. In one other embodiment, the output port of the reagent reservoir is configured to provide the reagent in the reagent reservoir to the biochip at least in part by being configured to be connectable to a channel that is configured to be connectable to the biochip.

[0012] In other embodiments, the biochip includes a nanopore -based biological assay chip. In one other embodiment, the reagent cartridge includes a plurality of reagent reservoirs. In one other embodiment, at least one side of a plurality of winding chambers of a plurality of reagent reservoirs is configured to contact the thermal source. In one other embodiment, the reagent reservoir is at least in part made of polypropylene. In one other embodiment, at least one side of the winding chamber is made at least in part of metal. In one other embodiment, at least one side of the winding chamber is made at least in part of a thermally conductive film. In one other embodiment, the thermally conductive film is a metallic foil that forms at least a part of each of a plurality of reagent reservoirs. In one other embodiment, the thermal source is a thermal electric cooling source. In one other embodiment, the thermal source is a thermal heating source. In one other embodiment, the reagent cartridge further comprises a vent port of the reagent reservoir. In one other embodiment, the reagent cartridge further comprises a lipid solvent reservoir. In a further embodiment, the lipid solvent reservoir has a surface area-to-volume ratio that is less than a surface area-to-volume ratio of the reagent reservoir. In one other embodiment, the cartridge is configured to be loaded on an instrument and removed from the instrument. In one other embodiment, the reagent cartridge includes the biochip mounted on a printed circuited board. In one other embodiment, the reagent cartridge includes a waste container.

[0013] In one other aspect, the present invention provides a mechanical engagement assembly or mechanical engagement device. In one embodiment, the mechanical engagement assembly comprises a shaft component and an end component. In one other embodiment, the end component is coupled to the shaft component. In a further embodiment, the end component is further configured to rotate together with the shaft component about a rotational axis of the shaft component but independently move with at least one degree of freedom relative to the shaft component. In one other embodiment, the at least one degree of freedom is associated with a compression or expansion of a length of the mechanical engagement assembly. In one other embodiment, the at least one degree of freedom is associated with a tilt of the end component relative to the shaft component. In one other embodiment, the end component is configured to independently move in only two degrees of freedom relative to the shaft component. In other embodiments, the end component comprises a tip, wherein the tip of the end component includes a feature configured to engage with a mechanical engagement interface of a selectable valve and rotate the mechanical engagement interface to select a selectable position of the selectable valve. In one other embodiment, the mechanical engagement interface and the selectable valve are included in a removable cartridge. In other embodiments, the mechanical engagement assembly is included in an instrument system configured to accept the removable cartridge. In another embodiment, the shaft component is coupled to an actuator that is configured to rotate the mechanical engagement assembly. In one other embodiment, the mechanical engagement assembly further comprises a spring coupled to at least the end component. In a further embodiment, the spring provides a force that pushes the end component away from the shaft component. In one other embodiment, a portion of the shaft component is tapered. In one other embodiment, a first portion of the shaft component is tapered in a first direction and a second portion of the shaft component is tapered in a second direction. In one other embodiment, the shaft component and the end component are made of different materials. In one other embodiment, the end component is made at least in part of brass. In one other embodiment, the tip of the end component includes a plurality of features configured to engage with the mechanical engagement interface. In a further embodiment, one feature of the plurality of features is a center feature that extends beyond another feature of the plurality of features. In one other embodiment, at least a portion of the end component is configured to at least partially enclose at least a portion of the shaft component configured to be inserted in the end component. In one other embodiment, the feature of the tip of the end component is configured to slip fit in a mating cavity of the mechanical engagement interface. In a further embodiment, a slope of a sidewall of the mating cavity is greater than a slope of a sidewall of the feature of the tip. In one other embodiment, the rotating (or the rotation) of the mechanical engagement interface to select the selectable position of the selectable valve includes rotating (or the rotation of) the end component until a home position of the selectable valve is detected. In one other embodiment, the mechanical engagement interface provides rotational torque to a gear component that rotates the selectable valve. In one other embodiment, the selectable valve is a part of a fluid delivery system for a sensor chip.

BRIEF DESCRIPTION OF THE DRAWINGS

[0014] Various embodiments of the invention are disclosed in the following detailed description and the accompanying drawings.

[0015] Figure 1 illustrates an embodiment of a cell 100 in a nanopore-based sequencing chip.

[0016] Figure 2 illustrates an embodiment of a cell 200 performing nucleotide sequencing with the Nano-SBS technique. [0017] Figure 3 illustrates an embodiment of a cell about to perform nucleotide sequencing with pre-loaded tags.

[0018] Figure 4 illustrates an embodiment of a process 400 for nucleic acid sequencing with pre-loaded tags.

[0019] Figure 5 is a schematic diagram illustrating an embodiment of at least a portion of a biological sensor system.

[0020] Figure 6 is a schematic diagram illustrating another embodiment of at least a portion of a biological sensor cartridge system.

[0021] Figures 7A-7D are schematic diagrams illustrating another embodiment of at least a portion of a biological sensor cartridge system. [0022] Figure 8A is a diagram illustrating an embodiment of a cartridge. [0023] Figure 8B is a diagram illustrating an embodiment of at least a portion of internal components of a cartridge.

[0024] Figure 8C is a diagram illustrating an embodiment of a cartridge and an instrument system that engages a cartridge. [0025] Figure 8D is a diagram illustrating an embodiment of a manifold assembly of a cartridge.

[0026] Figure 8E is a diagram illustrating an embodiment of an assembly of a cartridge being filled with a reagent.

[0027] Figure 9A is a diagram illustrating an embodiment of a radial valve assembly.

[0028] Figures 9B-9E are diagrams illustrating embodiments of a radial valve cartridge drawing and delivering content in various selectable radial valve positions.

[0029] Figures 10A-10G are diagrams illustrating embodiments of an end effector.

[0030] Figure 11 is a flowchart illustrating an embodiment of a process for flowing different types of materials through the cells of a nanopore-based sequencing biochip during different phases of the biochip operation.

DETAILED DESCRIPTION [0031] The invention can be implemented in numerous ways, including as a process; an apparatus; a system; a composition of matter; a computer program product embodied on a computer readable storage medium; and/or a processor, such as a processor configured to execute instructions stored on and/or provided by a memory coupled to the processor. In this specification, these implementations, or any other form that the invention may take, may be referred to as techniques. In general, the order of the steps of disclosed processes may be altered within the scope of the invention. Unless stated otherwise, a component such as a processor or a memory described as being configured to perform a task may be implemented as a general component that is temporarily configured to perform the task at a given time or a specific component that is manufactured to perform the task. As used herein, the term 'processor' refers to one or more devices, circuits, and/or processing cores configured to process data, such as computer program

instructions.

[0032] A detailed description of one or more embodiments of the invention is provided below along with accompanying figures that illustrate the principles of the invention. The invention is described in connection with such embodiments, but the invention is not limited to any embodiment. The scope of the invention is limited only by the claims and the invention encompasses numerous alternatives, modifications and equivalents. Numerous specific details are set forth in the following description in order to provide a thorough understanding of the invention. These details are provided for the purpose of example and the invention may be practiced according to the claims without some or all of these specific details. For the purpose of clarity, technical material that is known in the technical fields related to the invention has not been described in detail so that the invention is not unnecessarily obscured. [0033] A delivery system for a sensor chip is disclosed. For example, a biological assay (e.g., nucleotide/nucleic acid sequencing) chip requires fluids and/or gases to be provided on the sensor chip, and a delivery system provides at least a portion of the materials required to perform the assay. In some

embodiments, a plurality of selectable ports are arranged on a first assembly. Each selectable port is in communication with a separate channel. For example, each of the separate channels are connected to a different reagent, liquid, gas, waste container, etc. where material could be delivered/pushed or drawn/pulled. One of the separate channels may be connected to a biochip and material could be delivered/pushed or drawn/pulled to/from the biochip using this separate channel. [0034] In some embodiments, a second assembly is movable in relation to the first assembly and the second assembly has at least one channel that is mechanically connectable to different ones of the plurality of ports on the first assembly by motion of the second assembly relative to the first assembly. An example of the second assembly is a radial valve that is rotated by a motor to select a desired combination of multiple simultaneous connections of a least a portion the plurality of ports on the first assembly. For example, the second assembly is movable in relation to the first assembly to simultaneously connect a first channel of a plurality of channels of the second assembly to a first port of selectable ports of the first assembly and a second channel of the plurality of channels of the second assembly to a second port of the selectable ports of the first assembly. In some embodiments, the second assembly includes a plurality of channels. For example, in order to reduce contamination between different types of reagents and solvents to be utilized, certain types of reagents/solvents are designated to be drawn into one of the channels while other types of reagents/solvents are designated to be drawn into a different channel. In some embodiments, the second assembly includes one or more optical features to detect a position of the second assembly in relation to the first assembly. For example, in order to reliably and accurately position the second assembly to select and connect the plurality of ports in a desired

configuration, one or more optical patterns and/or optical openings are placed on the second assembly. An optical detector may detect the pattern and/or position of an opening on the second assembly to determine the rotational position of the second assembly.

[0035] In some embodiments, a mechanical engagement interface is configured to engage an actuator so that relative motion of the first assembly and the second assembly is affected by the actuator. For example, the second assembly includes a selection port that can be moved by an actuator/motor to be connected to any one of the plurality of selectable ports that are arranged on the first assembly. In this example, the selection port may be connected to only one port of the plurality of selectable ports of the first assembly at one time and the other selectable ports of the first assembly that are not connected to the selection port are sealed closed (e.g., sealed by the second assembly). In some embodiments, the selection port of the second assembly is connected to a pump and a

chamber/channel that are utilized to deliver/push and/or draw/pull materials to/from the selected port of the plurality of selectable ports of the first assembly.

[0036] In some embodiments, the first assembly and the second assembly are included in a cartridge. The cartridge is removable from an instrument system and another cartridge may be engaged with the instrument system. By utilizing a removable cartridge, the components of the cartridge may be replaced quickly and easily on the instrument system without the need to clean and reuse the components of the cartridge. For example, the cartridge may be replaced for each different biological sample to be assayed by the instrument system to reduce the risk of the first biological sample contaminating the second biological sample. In some embodiments, the cartridge includes a reservoir with a winding chamber. For example, the chamber is configured to be in an elongated tubular serpentine shape to increase the surface area-to-volume ratio of the chamber to maximize the surface area available to thermally interact with a thermal source (e.g., cooling and/or heating). At least one side of the winding chamber is a thermal interface that is thermally conductive and configured to contact a thermal source. For example, at least a portion of a sidewall of the winding chamber is made of a metal foil. The cartridge includes a user accessible port to fill and/or empty the reagent reservoir. For example, a self-sealing user port may be utilized to fill the winding chamber with a desired reagent. The cartridge includes a selectable output port in

communication with the reagent reservoir. For example, the output port is selectable by a radial valve of the cartridge to connect the reagent reservoir to a channel that allows a reagent stored in the reagent reservoir to be drawn and delivered to a nanopore sequencing biochip.

[0037] In some embodiments, an end effector coupled to the actuator engages the mechanical engagement interface to select desired position(s)/port(s) of the selectable valve. The end effector may be any assembly or component configured to mechanically interact with another object and/or environment. For example, the end effector is a mechanical engagement assembly coupled to a motor and allows movement of the motor to mechanically interact with an environment and/or object touched by the end effector. The end effector includes a shaft component and an end component that are coupled to together. The end component is configured to independently move with at least one degree of freedom from the shaft component. For example, the end component is an end cap that is fitted over an end of the shaft component with a pin joint, and the end component rides along tapered sides of the shaft to provide constrained side tilt degree of freedom of movement. In addition to or instead of the tilt degree of freedom of movement, the end component may be configured to contract and expand (e.g., move up and down) independent from the shaft component in the direction of a length of the shaft component to provide lengthwise degree of freedom of movement. In some embodiments, although the end component is configured to independently move with at least one degree of freedom relative to the shaft component to tolerate misalignment with the mechanical engagement interface of the selectable valve, the end component is not allowed a rotational degree of freedom (e.g., end component is rotationally fixed to the shaft component and the end component rotates together with the shaft component about a rotational axis of the shaft component). This allows a torque applied on the shaft component to be dependently transmitted to the end component to allow the end component to rotate the mechanical engagement interface of the selectable valve.

[0038] A tip of the end component includes a feature configured to engage with the mechanical engagement interface of the selectable valve and the tip is configured to rotate the mechanical engagement interface to select desired position(s)/port(s) of the selectable valve. For example, the mechanical engagement interface is on the cartridge that is removable from an instrument system that utilizes the end effector to engage a motor of the instrument system with a mechanical engagement interface of the cartridge and rotate the mechanical engagement interface. By allowing the end component of the end effector one or more degrees of freedom of movement relative to the shaft component, variances in location of the tip of the end effector with respect to the mechanical engagement interface due to manufacturing/assembly variances/tolerances and/or cartridge positioning variances are able to be tolerated. [0039] A nanopore -based sequencing biochip may be used for DNA sequencing. A nanopore-based sequencing chip incorporates a large number of sensor cells configured as an array. For example, an array of one million cells may include 1000 rows by 1000 columns of cells. Nanopore membrane devices having pore sizes on the order of one nanometer in internal diameter have shown promise in rapid nucleotide sequencing. When a voltage potential is applied across a nanopore immersed in a conducting fluid, a small ion current attributed to the conduction of ions across the nanopore can be observed. The size of the current is sensitive to the pore size.

[0040] Figure 1 illustrates an embodiment of a cell 100 in a nanopore-based sequencing chip. A membrane 102 is formed over the surface of the cell. In some embodiments, membrane 102 is a lipid bilayer. The bulk electrolyte 114 containing protein nanopore transmembrane molecular complexes (PNTMC) and the analyte of interest is placed directly onto the surface of the cell. A single PNTMC 104 is inserted into membrane 102 by electroporation. The individual membranes in the array are neither chemically nor electrically connected to each other. Thus, each cell in the array is an independent sequencing machine, producing data unique to the single polymer molecule associated with the PNTMC. PNTMC 104 operates on the analytes and modulates the ionic current through the otherwise impermeable bilayer.

[0041] With continued reference to Figure 1, analog measurement circuitry 112 is connected to a metal electrode 110 covered by a thin film of electrolyte 108.

The thin film of electrolyte 108 is isolated from the bulk electrolyte 114 by the ion- impermeable membrane 102. PNTMC 104 crosses membrane 102 and provides the only path for ionic current to flow from the bulk liquid to working electrode 110. The cell also includes a counter electrode (CE) 116, which is an

electrochemical potential sensor. The cell also includes a reference electrode 117.

[0042] In some embodiments, a nanopore array enables parallel sequencing using the single molecule nanopore-based sequencing by synthesis (Nano-SBS) technique. Figure 2 illustrates an embodiment of a cell 200 performing nucleotide sequencing with the Nano-SBS technique. In the Nano-SBS technique, a template 202 to be sequenced and a primer are introduced to cell 200. To this template- primer complex, four differently tagged nucleotides 208 are added to the bulk aqueous phase. As the correctly tagged nucleotide is complexed with the polymerase 204, the tail of the tag is positioned in the barrel of nanopore 206. The tag held in the barrel of nanopore 206 generates a unique ionic blockade signal 210, thereby electronically identifying the added base due to the tags' distinct chemical structures.

[0043] Figure 3 illustrates an embodiment of a cell about to perform nucleotide sequencing with pre-loaded tags. A nanopore 301 is formed in a membrane 302. An enzyme 303 (e.g., a polymerase, such as a DNA polymerase) is associated with the nanopore. In some cases, polymerase 303 is covalently attached to nanopore 301. Polymerase 303 is associated with a nucleic acid molecule 304 to be sequenced. In some embodiments, the nucleic acid molecule 304 is circular. In some cases, nucleic acid molecule 304 is linear. In some embodiments, a nucleic acid primer 305 is hybridized to a portion of nucleic acid molecule 304. Polymerase 303 catalyzes the incorporation of nucleotides 306 onto primer 305 using single stranded nucleic acid molecule 304 as a template.

Nucleotides 306 comprise tag species ("tags") 307.

[0044] Figure 4 illustrates an embodiment of a process 400 for nucleic acid sequencing with pre-loaded tags. At stage A, a tagged nucleotide (one of four different types: A, T, G, or C) is not associated with the polymerase. At stage B, a tagged nucleotide is associated with the polymerase. At stage C, the polymerase is in close proximity to the nanopore. The tag is pulled into the nanopore by an electrical field generated by a voltage applied across the membrane and/or the nanopore.

[0045] Some of the associated tagged nucleotides are not base paired with the nucleic acid molecule. These non-paired nucleotides typically are rejected by the polymerase within a time scale that is shorter than the time scale for which correctly paired nucleotides remain associated with the polymerase. Since the non- paired nucleotides are only transiently associated with the polymerase, process 400 as shown in Figure 4 typically does not proceed beyond stage B. [0046] Before the polymerase is docked to the nanopore, the conductance of the nanopore is -300 pico Siemens (300 pS). At stage C, the conductance of the nanopore is about 60 pS, 80 pS, 100 pS, or 120 pS corresponding to one of the four types of tagged nucleotides. The polymerase undergoes an isomerization and a transphosphorylation reaction to incorporate the nucleotide into the growing nucleic acid molecule and release the tag molecule. In particular, as the tag is held in the nanopore, a unique conductance signal (e.g., see signal 210 in Figure 2) is generated due to the tag's distinct chemical structure, thereby identifying the added base electronically. Repeating the cycle (i.e., stage A through E or stage A through F) allows for the sequencing of the nucleic acid molecule. At stage D, the released tag passes through the nanopore.

[0047] In some cases, tagged nucleotides that are not incorporated into the growing nucleic acid molecule will also pass through the nanopore, as seen in stage F of Figure 4. The unincorporated nucleotide can be detected by the nanopore in some instances, but the method provides a means for distinguishing between an incorporated nucleotide and an unincorporated nucleotide based at least in part on the time for which the nucleotide is detected in the nanopore. Tags bound to unincorporated nucleotides pass through the nanopore quickly and are detected for a short period of time (e.g., less than 10 ms), while tags bound to incorporated nucleotides are loaded into the nanopore and detected for a long period of time (e.g., at least 10 ms).

[0048] Figure 5 is a schematic diagram illustrating an embodiment of at least a portion of a biological sensor system. For example, the biological sensor system is a nanopore-based nucleotide sequencing system.

[0049] The sensor system includes cartridge 502. Cartridge 502 engages with an instrument system, interfaces with the instrument system, and functions together with the instrument system to perform a biological assay (e.g., nanopore- based nucleotide sequencing). In Figure 5, one or more of the components shown to be not included in cartridge 502 may be included on the instrument system. Cartridge 502 is removable from the instrument system and another cartridge may be engaged with the instrument system. By utilizing a removable cartridge, the components of the cartridge may be replaced quickly and easily on the instrument system without the need to clean and reuse the components of the cartridge. For example, the cartridge may be replaced for each different biological sample to be assayed by the instrument system.

[0050] Cartridge 502 includes biochip 504, radial valve 506, container 508, container 510 and container 512. Each of containers 508, 510 and 512 may hold a liquid, a reagent, a gas, a solid (e.g., suspended in liquid) and any other substance to be utilized in performing a biological measurement. For example, container 508 holds a lipid and solvent mix, container 510 holds a sample and pore/polymerase mix, and container 512 holds a StartMix. Container 510 and container 512 are sensitive to temperature changes and thermal block 514 is thermally coupled to containers 510 and 512. For example, thermal block 514 provides thermal cooling to contents of container 510 and container 512. In some embodiments, thermal block 514 provides thermal heating and/or cooling to raise, lower, and/or maintain a temperature of contents of container 510 and container 512. In the example shown, thermal block 514 is not a part of cartridge 502 and is a part of the instrument system. Biochip 504 may be the nanopore-based sequencing chip described elsewhere in the specification. Biochip 504 is electrically

connected/interfaced with the instrument system and electrical measurement data is read from biochip 504 and exported out of the biochip 504 to the instrument system for storage/analysis. For example, cartridge 502 includes a circuit board that provides electrical contact interfaces between biochip 504 and the instrument system. Biochip 504 is thermally coupled to the instrument system via a thermoelectric cooler (TEC)/heat sink assembly 516. The TEC/Heat sink assembly 516 allows the temperature of the biochip 504 to be controlled. For example the biochip and its fluid contents can be held at a constant temperature (e.g., warm or cold) and/or exposed to varying temperatures in a controlled manner (e.g., thermal cycling).

[0051] Radial valve 506 mechanically engages actuator/motor 518 of the instrument system. Actuator/motor 518 is separate from cartridge 502. In an alternative example, a motor is included in cartridge 502. Motor 518 actuates a movable assembly of radial valve 506 to select a desired port of radial valve 506. For example, motor 518 engages a movable assembly of radial valve 506 directly or indirectly via one or more gears, worm screws, or friction engagements (e.g., friction wheel).

[0052] Radial valve 506 includes central port 520 and selectable ports 521- 526 that are arranged coaxially in a rotary configuration. Radial valve 506 may be rotated via actuator/motor 518 to select one of selectable ports 521-526 as the active/open port. The other not selected ports of selectable ports 521-526 may or may not be automatically sealed/closed when the selected port is selected.

Materials may be passed between central port 520 and the selected port. For example, a fluid/gas passage channel is created between central port 520 and the selected port. Central port 520 is connected to interface 528 via channel 527 (e.g., tube). Interface port 528 is an interface of cartridge 502 where materials may enter/exit cartridge 502. Examples of interfaces of the cartridge include a needle septum, a flap valve or a ball displacement valve. Central port 520 is connected to pump 530 via interface 528. Pump 530 includes a syringe pump that may draw or push content into or out of pump chamber 532. Pump 530 includes a secondary radial value 534. In some embodiments, chamber 532 is a fluidic channel such as tubing. Pump 530 is a two-way pump that can deliver/push and draw/pull materials in to/out of pump chamber 532. [0053] Radial valve 534 may be configured to connect pump chamber 532 to any of selectable ports A-F as shown in Figure 5. Radial valve 534 may be rotated via an actuator/motor to select one of selectable ports A-F as the selected active/open port. The other not selected ports of selectable ports A-F are automatically sealed/closed when the selected port is selected. Liquid/gas may be passed between pump chamber 532 and the selected port of valve 534. Port A is connected to a salt buffer solution. Port B is connected to a surfactant solution. Port C is connected to a cleaning solution. Port D is connected to central port 520 via interface 528. For example, when port D is selected on radial valve 534, pump 530 is able to deliver/push any material in pump chamber 532 to a selected port of radial valve 506 and pump 530 is able to pull any material from the selected port of radial valve 506 into chamber 532. Port E is connected to a waste container where content in chamber 532 can be discarded. Port F is connected to an air vent. For example, ambient air can be drawn into chamber 532 when port F is selected on radial valve 534. In an alternative embodiment, rather than utilizing two radial valves, a single radial valve on cartridge 502 is utilized. For example, valve 506 may include additional ports for additional reagents and central port 520 is connected to pump chamber 532 without another intervening radial valve.

[0054] In some embodiments, by delivering/pushing and drawing/pulling various materials to/from the ports of radial valve 534 and/or radial valve 506 using pump 530 in a configured sequence, a biological assay is performed using biochip 504. For example, a reagent to be pushed into chip 504 may be placed in chamber

532 by selecting one of selectable ports A-C on valve 534 connected to a desired reagent, pumping content of the selected port into chamber 532, then selecting port D on valve 534 and selecting port 521 on valve 506, and pushing the content of chamber 532 to chip 504. In another example, a reagent to be pushed into chip 504 may be placed in chamber 532 by selecting port D on valve 534 and selecting one of selectable ports 522-524 on valve 506 connected to the desired reagent, pumping content of the selected port into pump chamber 532, then selecting port 521 on valve 506 and pushing the content of chamber 532 to chip 504. In another example, a reagent to be pushed into chip 504 may be drawn out of chambers 508, 510 or 512 by selecting the corresponding port 524, 523 or 522, and selecting port D on valve 534. In this example, a reagent is drawn into fluid channel 527, but not past fluid interface 528 which keeps the reagent within the cartridge and does not contaminate surfaces outside of the cartridge (e.g., pump chamber 532). Port 521 can then be selected on valve 506, and the reagent can be pushed into the chip 504. Often in the sequence, a material flowed on chip 504 needs to be discarded as a next material is flowed on chip 504. Interface 536 is an interface of cartridge 502 where waste materials to be discarded may exit cartridge 502. Material in the chamber of chip 504 may be pushed out of the chamber and into waste container 538 via chamber exit port 535 and interface 536. However in some cases, it may be desirable to be able to discard material without flowing the material to be discarded completely across chip 504 and out chamber port 535. In some embodiments, port 521 is selected on valve 506 and pump 530 pulls material out of the chamber of chip 504. Then port 526 is selected and the material to be discarded in pump chamber 532 is pushed out into waste container 538 via an alternative channel path that does not enter the chamber of chip 504 and does not include chamber port 535 yet still exits via interface port 536. Other materials pumped from other sources by pump 530 to be discarded may also be pushed into waste container 538 bypassing chip 504 via the alternative channel path. Examples of waste container 538 include a vented container, an expandable container, a one-way valve container, and an absorbent material filled container (e.g., to prevent flow back onto chip 504). In an alternative embodiment, waste container 538 is included in cartridge 502. [0055] The embodiment shown in Figure 5 is merely an example and has been simplified to illustrate the embodiment clearly. For example, the radial valves shown in Figure 5 may include any number of selectable ports. Additional components not shown in Figure 5 may also exist.

[0056] Figure 6 is a schematic diagram illustrating another embodiment of at least a portion of a biological sensor cartridge system. For example, the biological sensor cartridge system is a nanopore-based nucleotide sequencing system.

[0057] The sensor system includes cartridge 602. Cartridge 602 engages with an instrument system, interfaces with the instrument system, and functions together with the instrument system to perform a biological assay (e.g., nanopore- based nucleotide sequencing). In Figure 6, one or more of the components shown to be not included in cartridge 602 may be included on the instrument system. Cartridge 602 is removable from the instrument system and another cartridge may be engaged with the instrument system. By utilizing a removable cartridge, the components of the cartridge may be replaced quickly and easily on the instrument system without the need to clean and reuse the components of the cartridge. For example, the cartridge may be replaced for each different biological sample to be assayed by the instrument system.

[0058] Cartridge 602 includes biochip 604 in a chamber, radial valve 606, and containers 608, 610, 612, 640, 642, and 644. Each of containers 608, 610, 612, 640, 642 and 644 may hold a liquid, a reagent, a gas, a solid (e.g., suspended in liquid), and any other substance to be utilized in performing a biological measurement. For example, container 608 holds a lipid and solvent mix, container 610 holds a sample and pore/polymerase mix, container 612 holds a StartMix, container 640 holds a cleaning solution, container 642 holds a surfactant solution, and container 644 holds a salt buffer solution. In some embodiments, container 610 and container 612 are sensitive to temperature changes and a thermal block provides thermal heating and/or cooling to raise, lower, and/or maintain a temperature of contents of container 610 and container 612. Biochip 604 may be the nanopore-based sequencing chip described elsewhere in the specification.

Biochip 604 is electrically connected/interfaced with the instrument system and electrical measurement data is read from biochip 604 and exported out of the biochip 604 to the instrument system for storage/analysis. For example, cartridge 602 includes a circuit board that provides an electrical contact interface between biochip 604 and the instrument system. Biochip 604 is thermally coupled to the instrument system via TEC/heat sink assembly 616. TEC/heat sink assembly 616 allows thermal energy of biochip 604 to be dissipated via assembly 616.

[0059] Radial valve 606 mechanically engages actuator/motor 618 of the instrument system. Actuator/motor 618 is separate from cartridge 602. Motor 618 actuates a movable assembly of radial valve 606 to select a desired port of radial valve 606. For example, motor 618 engages a movable assembly of radial valve 606 directly or indirectly via one or more gears, worm screws, or friction engagements (e.g., friction wheel).

[0060] Radial valve 606 includes central port 620 and selectable ports 621- 628 that are arranged coaxially in a rotary configuration. Radial valve 606 may be rotated via actuator/motor 618 to select one of selectable ports 621-628 as the active/open port. The other not selected ports of selectable ports 621-628 are automatically sealed/closed when the selected port is selected. Selectable port 628 is connected to an air vent. For example, ambient air can be drawn into chamber 632 when port 628 is selected on radial valve 606. Materials may be passed between central port 620 and the selected port. For example, a fluid/gas passage channel is created between central port 620 and the selected port. Central port 620 is connected to pump chamber 632. In some embodiments, the pump chamber is located external to cartridge 602 and central port 620 is connected to the external pump chamber via an interface port of cartridge 602 connected to central port 620 via a channel (e.g., tube). Pump chamber 632 is a part of a two-way pump (e.g., syringe pump, peristaltic pump, etc.) that may draw or push content into or out of pump chamber 632. In some embodiments, pump chamber 632 is a fluidic channel such as tubing.

[0061] A piston of pump chamber 632 mechanically engages a moveable assembly of actuator/motor 630 of the instrument system directly or indirectly via one or more gears, worm screws, or friction engagements. The push/pull action of the syringe pump is controlled by actuating actuator/motor 630. Materials may be passed between pump chamber 632 and the selected port of valve 606. For example, material may be pushed into chamber 632 from a selected port of valve 606 and material in chamber 632 may be pushed out of chamber 632 to a selected port of valve 606.

[0062] In some embodiments, by delivering/pushing and drawing/pulling various materials to/from the ports of radial valve 606 using the pump of chamber 632 in a configured sequence, a biological assay is performed using biochip 604. For example, a reagent to be delivered/pushed into chip 604 may be placed in chamber 632 by selecting one of selectable ports 622-628 on valve 606 connected to a desired reagent/gas, pumping content of the selected port into pump chamber 632, then selecting port selecting port 621 on valve 606 and pushing the content of pump chamber 632 to chip 604. [0063] Often in the sequence, a material flowed on chip 604 needs to be discarded as a next material is flowed across chip 604 to exit the chamber of 604. Material in the chamber of chip 604 may be pushed out of the chamber via chamber port 651 and into waste container 638. However in some cases, it may be desirable to be able to discard material without flowing the material to be discarded completely across chip 604 to exit via chamber port 651. In some embodiments, port 621 is selected on valve 606 and material on the chip is pumped into pump chamber 632, then pushed out into waste container 638 via bypass channel path 654 that does not enter the chamber of chip 604. Three-way valve 650 may be switched to either connect port 621 with only the chamber of chip 604 or with only bypass channel 654, as appropriate. In an alternative embodiment, rather than using three-way valve 650, the chamber of chip 604 is always connected to port 621 (e.g., without three-way valve 650) and a bypass selectable port on radial valve 606 (e.g., alternative embodiment shown as selectable port 660) is always connected to bypass channel 654 to allow a connection between pump chamber 632 and waste container 638 without passing through the chamber of chip 604 when the bypass selectable port is selected. Other materials pumped from other sources (e.g., during initial priming) by the pump of chamber 632 to be discarded may also be pushed into waste container 638 via bypass channel 654. Examples of waste container 638 include a vented container, an expandable container, a one-way valve container, and an absorbent material filled container. Two-way valve 652 may be configured to switch between allowing or not allowing flow between its connected channels.

By opening valve 652, material in the chamber of chip 604 may be directly pushed out into waste container 638. By closing valve 652, backflow on to chip 604 may be prevented when pushing waste into container 638 via bypass channel 654 or when waste content leaks out of waste container 638. The ability to close valve 652 may also enable the pump to pressurize the fluid or gas on chip 604. In some embodiments, valve 652 is optional. In an alternative embodiment, valve 652 is a one-way valve. In alternative embodiments, a plurality waste containers are utilized. For example, one waste container is connected to receive waste from chip outlet 651 while another waste container is connected to receive waste via bypass channel 654.

[0064] The embodiment shown in Figure 6 is merely an example and has been simplified to illustrate the embodiment clearly. For example, the radial valves shown in Figure 6 may include any number of selectable ports. Additional components such as other valves not shown in Figure 6 may also exist. In some embodiments, linear valve 700 is included in cartridge 502 of Figure 5. In some embodiments, linear valve 700 is included in cartridge 602 or Figure 6. [0065] Figures 7A-7D are schematic diagrams illustrating another embodiment of at least a portion of a biological sensor cartridge system. For example, the biological sensor cartridge system is a nanopore-based nucleotide sequencing system. [0066] The sensor system includes cartridge 702. Cartridge 702 engages with an instrument system, interfaces with the instrument system, and functions together with the instrument system to perform a biological assay (e.g., nanopore- based nucleotide sequencing). The bottom side of cartridge 702 may expose electrical contacts that allow electrical connection between one or more electrical components of cartridge 702 and the instrument system to be engaged with cartridge 702. The electrical contacts of the cartridge electrically interface with the instrument system via electrical connector 755. Cartridge 702 is removable from the instrument system and another cartridge may be engaged with the instrument system. By utilizing a removable cartridge, the components of the cartridge may be replaced quickly and easily on the instrument system without the need to clean and reuse the components of the cartridge. For example, the cartridge may be replaced for each different biological sample to be assayed by the instrument system.

[0067] Cartridge 702 includes biochip 704, radial valve 706, and reservoirs/containers 708, 710, 712, and 740 that are vented. Each of reservoirs 708, 710, 712, and 740 may hold a liquid, a solvent, a reagent, a gas, a solid (e.g., suspended in liquid), and any other substance to be utilized in performing a biological measurement. For example, reservoir 708 holds a lipid and solvent mix, reservoir 710 holds a sample and pore/polymerase mix, reservoir 712 holds a StartMix and reservoir 740 is a reserved spare reservoir. In some embodiments, at least reservoir 710 and reservoir 712 are sensitive to temperature changes and thermal block 742 provides thermal heating and/or cooling to raise, lower, and/or maintain a temperature of contents of reservoir 710, reservoir 712, and reservoir 740. Reservoirs 708, 710, 712, and 740 are each connected to a different selectable port that can be selected by radial valve 706. The channel paths connecting each reservoir to a corresponding selectable port includes a pipette port that can be utilized to fill/extract or deliver material to the corresponding reservoir and/or selectable port.

[0068] Biochip 704 may be the nanopore-based sequencing chip described elsewhere in the specification. Biochip 704 is electrically connected/interfaced with the instrument system via electrical connector 755 and electrical measurement data is read from biochip 704 and exported out of the biochip 704 to the instrument system for storage/analysis. Biochip 704 is thermally coupled to the instrument system via thermal block 716. Thermal block 716 allows thermal energy of biochip 704 to be dissipated via thermal block 716.

[0069] Radial valve 706 mechanically engages actuator/motor 718 of an instrument system. Actuator/motor 718 is separate from cartridge 702. Motor 718 actuates a movable assembly of radial valve 706 to connect one or more desired ports of radial valve 706. For example, motor 718 engages a movable assembly of radial valve 706 directly or indirectly via one or more gears, worm screws, or friction engagements (e.g., friction wheel). [0070] Radial valve 706 includes central port 720 and can be placed in any one of shown selectable positions 1-8 that are arranged in a rotary configuration. Other selectable positions may exist and the shown example has been simplified to illustrate the embodiment clearly. These selectable positions are merely an example and other selectable positions and configurations may exist in other embodiments. Radial valve 706 is rotated via actuator/motor 718 to select one of selectable positions 1-8. A moveable radial valve assembly of radial valve 706 includes one or more ports that can be connected with other fixed selectable ports of cartridge 702 that are not on the moveable assembly of radial valve 706. Each position of the selectable radial valve positions corresponds to a different configuration of connection(s) and disconnection(s) between the port(s) of the moveable assembly of radial valve 706 and the selectable ports of cartridge 702. For example, positions 3-6 each correspond to a different selectable port that can be selected to connect to a port on the moveable assembly of radial valve 706. The other not selected ports are automatically sealed/closed when the selected port is selected.

[0071] Using positions 1 and 2 of radial valve 706, a direct connection between outlet port 735 of the chamber of chip 704 and port 736 connected to a waste container is controlled in addition to controlling a connection between a port on the moveable assembly of radial valve 706 and the inlet port of the chamber of chip 704. In some embodiments, by allowing a single selectable valve to control multiple connections between different sets of ports, a more efficient cartridge design may be achieved due to the multiple functions being performed by the selectable valve. For example, rather than using valve 652 of Figure 6, a single selectable valve such as valve 706 may be utilized to perform the functions of both radial valve 606 and valve 652 of Figure 6. [0072] The exact rotational/selected position of radial valve 706 is determined using optical detector 760 (e.g., break beam sensor). For example, by reading/detecting an optical pattern and/or opening on a moveable assembly of radial valve 706, optical detector 760 converts the detected pattern/opening corresponding to a specific position of the moveable assembly to an electrical signal/code that can be utilized to determine the specific valve position. For example, a moveable assembly of radial valve 706 includes a pattern and/or opening that selectively blocks or allows light at specific rotation locations to indicate a rotational position of the moveable assembly within cartridge 702. In some embodiments, a known "home" position of the radial valve is identified (e.g., using the optical detector 760 or other ways in alternative embodiments) and an open loop control is utilized to rotate the radial valve a controlled amount (e.g., specified number of degrees).

[0073] Channel 722 of radial valve 706 connects central port 720 to ports of channel 722 (e.g., channel 722 has multiple ports as shown by circles on channel 722). When the moveable assembly of valve 706 is rotated, channel 722 is physically rotated together. For example, channel 722 is molded in the moveable assembly that rotates as a part of radial valve 706. In addition to channel 722, channel 723 and channel 724 are also included in the moveable assembly and are also rotated together when the moveable assembly of radial valve 706 is rotated (e.g., included in the moveable assembly). However, channel 723 and channel 724 are not directly connected to central port 720 on the moveable assembly of radial valve 706. The sizes of the channels shown are not to scale and have been shown to illustrate the existence of the channels rather than the relative or absolute sizes of the channels. For example, channel 722 and channel 723 are similar in size in some embodiments. Channel 724 selectively connects chamber outlet port 735 of the chamber of chip 704 with port 736 of the waste container. Channel 722 and channel 723 are utilized to store and deliver content via selection ports on the respective channels. For example, syringe pump 730 is connected to central port 720 and when syringe pump 730 applies vacuum/negative pressure to draw contents, channel 722 is filled with contents from any of its ports connected to a content source corresponding to a selectable position of radial valve 706. Then at another selectable position of radial valve 706, syringe pump 730 applies positive pressure to deliver content in channel 722 via any of its connected ports (e.g., connected to chip port 733, waste container, etc.).

[0074] Thus channel 722 is able to be utilized as an intermediary container to hold various reagents, gases, and solvents that are drawn from various reservoirs selected in various selectable positions of radial valve 706 to be delivered to a biochip in other selectable positions of radial valve 706. However, certain reagents, gases, or solvents may contaminate other reagents, gases, or solvents and it may be desirable to not utilize the same channel for certain reagents, gases, or solvents with certain other reagents, gases, or solvents. For example, aqueous materials (e.g., reagents) are not to be contaminated by non-aqueous materials (e.g., lipid and oil-based solvents, decane, hydrophobic/oleophobic materials, etc.) and channel 722 is to be utilized to hold aqueous materials while channel 723 is to be utilized to hold non- aqueous materials. Channel 723 is not directly connected to central port 720 in the moveable assembly of rotatory valve 706 and only when contents are to be drawn into or delivered from channel 723 (via a port on channel 723 that has been connected to a selectable port selected by rotation of rotatory valve 706) is channel 723 in communication with the vacuum/negative pressure provided by syringe pump 730 via central port 720 and channel 722. Thus, when channel 723 is to be utilized to draw or deliver contents, channel 723 is connected to channel 722. Channel 723 is only connected to channel 722 at only certain selectable positions of radial valve 706. Cartridge 702 includes one or more cross-over channels (e.g., channel fixed to cartridge 702) that connect channel 722 and channel 723 when radial valve 706 is rotated to certain selectable position(s). An example of the cross-over channel is cross-over channel 713.

[0075] Figure 7A shows radial valve 706 in position "1." In this position, central port 720 is connected to a port on channel 722 that is connected to inlet port

733 (e.g., two-way port) of the chamber of chip 704, allowing materials to be passed between channel 722 and the chamber of chip 704. However, channel 724 does not connect any ports in position "1." Thus, chamber outlet port 735 of the chamber of chip 704 is sealed and not connected to port 736 of the waste container. This may allow chip 704 and contents of the chamber to be pressurized. Figure 7B shows radial valve 706 in position "2." In this position, channel 722 is still connected to inlet port 733 of the chamber of chip 704 but via a different port on channel 722. However, ports of channel 724 now connect chamber outlet port 735 of the chamber of chip 704 with port 736 of the waste container, allowing waste to flow from the chip chamber to the waste container. Figure 7C shows radial valve

706 in position "3." In this position, channel 722 is connected to an air vent via another port of channel 722. Channel 724 does not connect to any ports in position "3."

[0076] Figure 7D shows radial valve 706 in position "4." In this position, a port of channel 723 is connected to a selectable fixed port corresponding to lipid reservoir 708. Channel 723 is also connected to channel 722 via cross-over channel 713. Thus the pressure of syringe pump 730 via central port 720 is in

communication with channel 723 via channel 722, allowing a vacuum pressure of syringe pump 730 to cause contents of lipid reservoir 708 to be drawn into channel 723. In some embodiments, only a limited amount/time of vacuum/negative pressure is applied to not allow contents being drawn into channel 723 to enter channel 722. For example, channel 722 is to be utilized to draw and hold aqueous materials (i.e., non-aqueous materials are not be stored) in reservoirs 710, 712 and 740 (e.g., by directly connecting a port on channel 723 to a corresponding selectable fixed port of a desired reservoir), while channel 723 is to be utilized to draw and hold the non-aqueous materials (i.e., aqueous materials are not be stored) in reservoir 708 to avoid cross-contamination. In some embodiments, a port on channel 723 can be rotated via rotation of radial valve 706 to connect to outlet port 735 to deliver contents in channel 723 to the chamber of chip 704 via its outlet port 735 to avoid contaminating inlet port 733 of chip 704 with the contents of channel 723 (e.g., aqueous content delivered to chip via inlet port 733 and non-aqueous content delivered to chip via outlet port 735).

[0077] Central port 720 is connected to interface 728 via a channel (e.g., tube). Interface port 728 is an interface of cartridge 702 where materials may enter/exit cartridge 702. In the example shown, a needle septum is utilized as the interface port. Central port 720 is connected to pump 730 via interface 728. Pump

730 includes a syringe pump that may draw or push content into or out of pump chamber 732. Pump 730 includes a secondary radial value. In some embodiments, chamber 732 is a fluidic channel such as tubing. Pump 730 is a two-way pump that can deliver/push and draw/pull materials in to/out of pump chamber 732. In some embodiments, pump 730 functions in a similar manner as pump 530 of Figure 5.

Position "8" of radial valve 706 corresponds to a selection of a bypass waste selectable port that allows a connection between central port 720 and a waste container without passing through the chamber of chip 704 when the bypass waste selectable port is selected. [0078] Figure 8A is a diagram illustrating an embodiment of a cartridge. In some embodiments, cartridge 802 shows at least a portion of features of cartridge 502 of Figure 5, cartridge 602 of Figure 6 and/or cartridge 702 of Figures 7A-7D.

[0079] The bottom side of cartridge 802 exposes electrical contacts 804.

Electrical contacts 804 allow electrical connection between one or more electrical components of cartridge 802 and an instrument system to be engaged with cartridge 802. For example, electrical data (e.g., electrical measurement/reading data) of the biochip may be accessed/provided/received via electrical contacts 804 by the instrument system to determine a result of a biological assay. In some embodiments, electrical contacts 804 are contacts of a circuit board included in cartridge 802 and the circuit board is electrically connected to a biochip. [0080] Thermal chip interface 806 provides a thermal interface where a heat sink or a thermal block (e.g., thermal block 716 of Figures 7A-7D) can be thermally coupled to a biochip included in cartridge 802. For example, the heat sink allows thermal energy of the biochip to be dissipated via the heat sink. In another example, a thermal block sink allows the biochip to be actively cooled via the thermal block (e.g., thermal electric cooling). The heat sink or thermal block may be a part of the instrument system that receives cartridge 802. Cartridge 802 includes interface port 808. In some embodiments, interface port 808 is interface port 528 of Figure 5. In some embodiments, interface port 808 is connected to a central port of a radial valve (e.g., central port 520 of Figure 5, port 620 of Figure

6, or port 720 of Figures 7A-7D) and/or a syringe pump. Drive engagement interface 812 is configured to engage with an actuator/motor to operate a selectable radial valve. For example, a selection of a selected valve position among a plurality of selectable valve positions is performed by mechanically actuating an

engagement mechanism (e.g., gear) via engagement interface 812.

[0081] Cartridge 802 includes thermally controlled reservoirs 814 and 816 shown as winding serpentine chambers. Reservoir 818 is not to be thermally controlled. Reservoirs 814, 816, and 818 may hold a liquid, a reagent, a gas, a solid (e.g., suspended in liquid), and any other substance to be utilized in performing a biological measurement. For example, reservoir 814 holds a StartMix and reservoir 816 holds a sample and pore/polymerase mix and reservoir 818 holds a lipid and solvent mix. Contents of reservoirs 814, 816, and 818 are connected to selectable ports of a selectable valve via separate channels and the contents of the containers may be drawn for use during a biological assay via the corresponding selectable valve. Reservoirs 814 and 816 may be thermal-controlled using a thermal block

(e.g., thermally controlled using refrigerant, ice, Freon, thermal-electric, etc.) that interfaces with a bottom wall surface of the reservoirs to reduce and/or maintain a temperature of its contents (e.g., via thermal conduction through bottom walls of reservoirs 814 and 816). The exposed bottom wall external surface of reservoirs 814 and 816 is shown as surface 810. When cartridge 802 is placed in an instrument system, surface 810 contacts a thermal block to maintain a temperature of the contents of the reservoirs. Surface 810 may be made of a thermally conductive material (such as a metallic foil, e.g., an aluminum foil) that forms at least a portion of a bottom wall of a chamber of a reservoir.

[0082] Figure 8B is a diagram illustrating an embodiment of at least a portion of internal components of a cartridge. In some embodiments, one or more components shown in Figure 8B are included in cartridge 502 of Figure 5, cartridge

702 of Figures 7A-7D and/or cartridge 602 of Figure 6.

[0083] The cartridge includes septum 820 (e.g., septum 728) that connects a pump (e.g., syringe pump) to the cartridge (e.g., provides an interface between a central port of a radial valve to the pump). The cartridge includes drive gear 821 that includes a motor engagement interface and gear teeth that engage and rotate gear teeth of a radial valve of the cartridge. For example, when the cartridge is loaded on an instrument, a motor of the instrument engages with the motor engagement interface of drive gear 821 to turn drive gear 821. The teeth of drive gear 821 engage with teeth of the radial valve 832 to turn the radial valve 832. The cartridge includes absorber sheet 822. The cartridge includes cartridge frame 823 that houses and holds together various components of the cartridge.

[0084] Radial valve retainer 824 aligns and holds radial valve assembly 832 to allow radial valve assembly 832 to rotate in place. Radial valve retainer 824 includes a plurality of holes that correspond to selectable ports on manifold assembly 831. Radial valve assembly 832 includes a plurality of channels with ports. For example, at least a portion of the channels have been molded on to radial valve assembly 832 and sealed with cover material that seals the channels. Each of these channels has an opening on the top and/or bottom of radial valve assembly 832 that allow contents to flow in/out of the channel. [0085] Manifold seal gasket 825 provides a seal on selectable ports of manifold assembly 831 that are selectable by rotation of radial valve assembly 832. The port seals of manifold seal gasket 825 provide seals and passages between the selected ports of manifold assembly 831 and corresponding top ports on radial valve assembly 832. The not selected ports of manifold assembly 831 and top ports on radial valve assembly 832 are sealed by manifold seal gasket 825. The ports of the bottom of radial valve assembly 832 can be connected to selectable ports by rotating the radial valve assembly 832 to a desired position. For example, ports of the bottom of radial valve assembly 832 are utilized to connect to input and output ports of chip 836. Valve bottom seal gasket 826 seals one or more bottom ports of radial valve assembly 832 in certain positions of radial valve assembly 832.

Manifold seal gasket 825 and valve bottom seal gasket 826 may be made of elastomeric material (e.g., synthetic rubber).

[0086] Manifold assembly 831 forms at least a portion of a plurality of reservoirs and channels. For example, manifold assembly 831 has been injection molded using polypropylene to form top portions of walls of channels and reservoirs. At least a portion of the bottom of manifold assembly 831 has been sealed (e.g., heat sealed, glued or other bonding method) with a thermally conductive material (e.g., thin film) to enclose the walls of channels and reservoirs. For example, the bottom of manifold assembly 831 has been sealed with a heat seal film (e.g., heat seal metal foil). In some embodiments, at least a portion of a material coupled to manifold assembly 831 forming a bottom (e.g., 810 of Figure 8A) of one or more reservoirs of assembly 831 is a thermally conductive material and configured to make contact and interface with a thermal block when the cartridge is loaded on an instrument. For example, the bottom of manifold assembly 831 has been sealed with a metal foil to create a bottom wall of a plurality of reservoirs. Content placed in the reservoirs may need to be maintained at a certain temperature and a thermal cooling/heating source may be placed in contact with the thermally conductive bottom wall of the reservoirs to control the temperature of contents in the reservoirs. [0087] Entry port interface 827 is held on to manifold assembly 831 using entry port retainer 828 and provides an interface where reservoirs of manifold assembly 831 may be filled (e.g., using a pipette inserted in entry port interface 827). Manifold assembly 831 includes a secondary type of reservoir that is covered by cap 834. This secondary type has a reduced surface area-to-volume ratio as compared to one or more other reservoirs of the cartridge. Reservoir vent cover 835 covers an air vent of a reservoir to protect the opening while allowing air to enter and escape the reservoir.

[0088] Circuit board 829 is electrically coupled to biochip 836. In various embodiments, biochip 836 is biochip 504 of Figure 5, biochip 604 of Figure 6, and/or 704 of Figures 7A-7D. The bottom side of circuit board 829 includes electrical contacts 804 shown in Figure 8 A. Chip insert 830 provides port interfaces between input and output ports of biochip 836 and bottom ports on radial valve assembly 832. The cartridge includes counter electrode contact wire assembly 833.

[0089] Figure 8C is a diagram illustrating an embodiment of a cartridge and an instrument system that engages a cartridge. In various embodiments, cartridge 802 is cartridge 502 of Figure 5, cartridge 602 of Figure 6, and/or cartridge 702 of

Figures 7A-7D. Figure 8C shows a portion of instrument 840 along with a blowup view to illustrate the interface between cartridge 802 and a pump needle interface.

[0090] Cartridge 802 may be received by instrument 840 and clamped down to engage cartridge 802 with instrument 840. Cartridge 802 may be removed from instrument 840 after use and another cartridge may be engaged with instrument 840 for a different sample. In some embodiments, instrument 840 is at least a portion of a system utilized to perform a biological assay (e.g., nucleotide sequencing). Instrument 840 includes electrical connectors that can be coupled with electrical contacts 804 shown in Figure 8A. Electrical connections between a biochip included in cartridge 802 and one or more electrical components of instrument 840 are established via the electrical connectors. Instrument 840 includes a chip cool block that is to interface with the biochip included in cartridge 802 to maintain a chip temperature. Instrument 840 also includes a reagent cooling block configured to interface with a thermally conductive wall/surface of reagent reservoirs (e.g., via 810 of Figure 8A) and provide a thermal source to thermally control (e.g., cool/heat) the contents of the reservoirs. The supply needle connected to a syringe pump is shown in the blowup view (cooling block removed from view to more clearly show the supply needle) and is inserted in interface port 808 (e.g., septum 728, 820) of cartridge 802 when the cartridge is engaged (e.g., inserted cartridge is lowered). The alignment pins help guide cartridge 802 when the cartridge is lowered into the instrument. The shown valve drive end effector 850 is connected to a motor and interfaces with a mechanical engagement interface of a drive gear (e.g., interface 812 of gear 821 shown in Figures 8A and 8B) in cartridge 802. Rotation of the valve drive end effector rotates the engaged drive gear and rotates the radial valve of cartridge 802 to select one or more positions of the radial valve.

[0091] The instrument includes an LED light source that is utilized to detect rotational position of the radial valve. For example, cartridge 802 includes one or more windows that allows molded openings on a radial valve assembly being rotated to align with the windows at certain rotational positions of the radial valve assembly. When the opening on the radial valve assembly aligns with the windows of the cartridge (e.g., openings viewable through the windows), light is allowed to pass through the cartridge via the windows and the opening. By shining the LED light source on the cartridge on one side of the cartridge and detecting the radial valve position at which the light source is viewable on the other side of the cartridge via the aligned opening and windows, a position of the radial valve is detected.

[0092] Figure 8D is a diagram illustrating an embodiment of a manifold assembly of a cartridge. In various embodiments, assembly 831 shows at least a portion of features of a cartridge (e.g., cartridge 802 is cartridge 502 of Figure 5, cartridge 602 of Figure 6, and/or cartridge 702 of Figures 7A-7D). The shown assembly 831 is manifold assembly 831 of Figure 8B.

[0093] Assembly 831 includes at least portions of molded reservoir chambers and channels. In some embodiments, the shown reagent 1 reservoir corresponds to reservoir 710, reagent 2 reservoir corresponds to reservoir 712 and reagent 3 reservoir corresponds to reservoir 740 of Figures 7A-7D. Each of these reservoirs have been configured in a winding shape (e.g., serpentine shape). For example, the chamber of the reservoir is configured to be in an elongated tubular serpentine shape to increase the surface area-to-volume ratio of the chamber to maximize the surface area available to thermally interact with a refrigeration source. The winding shape (e.g., winds on itself) allows the elongated tubular serpentine chamber to be wound within a limited rectangular area available to be thermally controlled. In some embodiments, the surface area-to-volume ratio of a reagent reservoir is greater than 1.5 mm ² / μΐ _^ (e.g., 2.2 mm ² / μΐ,).

[0094] At least one side of the winding reservoir is a thermal interface that is thermally conductive and configured to contact a thermal source (e.g., cooling/heating). For example, at least a portion of a bottom wall of the chamber of the reservoir is made of a metal foil. The top and side walls of the reservoir have been injection molded from polypropylene as assembly 831 and at least a portion of the bottom surface of assembly 831 has been attached to a thermally conductive material (e.g., heat sealed metal foil) to form a bottom wall of the chambers of the reservoirs as well as to provide a thermal interface that will conduct heat/cooling between the contents of the reservoirs and a thermal block touching the thermally conductive material.

[0095] The shown lipid-solvent reservoir is cylindrical in shape as compared to the winding shape of the reagent reservoirs. This allows the lipid- solvent reservoir to have a reduced surface area-to-volume ratio as compared to the elongated tubular serpentine shape of the reagent reservoirs. Because non-aqueous materials such as oil-based solvents have a tendency to self-migrate to various locations, the reduced surface area-to-volume ratio of the reservoir allows better control of the non-aqueous materials. In some embodiments, the surface area-to- volume ratio of the lipid-solvent reservoir is less than 2 mm ² / μΐ _^ . Additionally, the lipid-solvent reservoir does not need to be temperature controlled as compared to the reagent reservoirs and consequently does not require the higher surface area-to- volume ratio of the reagent reservoirs utilized to increase the surface area in contact with a thermal block. [0096] Assembly 831 includes a syringe pump channel that is to be connected to a central port (e.g., port 720 of Figures 7A-7D) of a radial valve assembly and a syringe pump (e.g., via septum 728 of Figures 7A-7D or 820 of Figure 8B and the supply needle shown in Figure 8C). The syringe pump channel is always connected to the radial valve regardless of the rotated position of the radial valve. In some embodiments, at least a portion of contents drawn by a connected syringe pump is stored in one or more channels of a radial valve as well as in the shown syringe pump channel. The shown crossover channels provide a connection between channels on a radial valve assembly. For example, one of the shown crossover channels corresponds to cross over channel 713 of Figure 7D that connects channel 722 with 723 when the ports of the channels are aligned with the ports of the crossover channel.

[0097] The top and side walls of the various channels shown in assembly

831 have been formed from injected molded material of assembly 831 and at least a portion of the bottom surface of assembly 831 has been attached to a sheet/film material (e.g., same heat sealed metal foil utilized to enclose reagent reservoirs) to form a bottom wall of the various channels. Various openings have been placed to provide ports on the various channels and reservoirs.

[0098] Radial valve position detection optical windows 841 and 842 are openings in assembly 831 that allow light to pass through assembly 831. A radial valve assembly under assembly 831 in a cartridge includes a pattern of openings that have been molded into the radial valve assembly. When the radial valve assembly is rotated to certain positions that align the one or more openings on the radial valve assembly with windows 841 and/or 842, light is allowed to pass through the cartridge and is detected by a sensor (e.g., break beam sensor) on an instrument to determine a position/orientation of the radial valve assembly inside the cartridge.

[0099] Assembly 831 includes an input port for each reagent reservoir. For example, an input port is utilized to fill the winding chamber of a reagent reservoir with a desired reagent. In some embodiments, by shaping the chamber of the reagent reservoir in the elongated tubular shape, content can be filled and extracted from the chamber in a manner that reduces air pockets inside the reservoir chamber. For example, when the reagent reservoir chamber is filled with a reagent, the reagent tends to remain in place and not uncontrollably migrate all around the reservoir due to the surface tension inside the chamber. Each of the shown reagent chambers are filled (e.g., backed in) via the shown reagent reservoir input ports. The shown reagent reservoir vents allow air to pass in and out of the corresponding chambers of the reagent reservoirs. [00100] Figure 8E is a diagram illustrating an embodiment of an assembly of a cartridge being filled with a reagent. In various embodiments, assembly 831 shows at least a portion of the features of a cartridge (e.g., cartridge 802 is cartridge 502 of Figure 5, cartridge 602 of Figure 6 and/or cartridge 702 of Figures 7A-7D). [00101] Figure 8E shows a pipette being used to fill a reagent reservoir via a reagent input port. The chamber of the reagent reservoir is filled front to back as a reagent provided by the pipette travels down the length of the serpentine chamber and pushes out air in the chamber via the vent at the end of the chamber. Due to the surface tension of the content of the reagent, the reagent fills the chamber completely at each successive length down the chamber without migrating uncontrollably and without leveling in the chamber horizontally. This may allow the reagent reservoir to be filled with a reagent utilized in a first-in- first-out manner. When the reagent reservoir chamber is filled via its input port, the filled contents bypass a selectable exit port (shown as outlet to radial valve on bottom side) of the reagent reservoir that can interface with a port of a radial valve assembly to provide contents of the reagent reservoir chamber to a channel on the radial valve assembly. For example, one end of the long reagent reservoir is a reagent input port and other end is an air vent. The selectable exit port of the reagent reservoir is located close to the reagent input port on the fluid pathway between the input port and a temperature controlled chamber of the reagent reservoir.

[00102] The shown bottom side view shows a metal foil that has been heat sealed on to assembly 831 to form bottom walls of reservoirs and channels. At least a portion of the shown metal foil under the reagent reservoir chambers may be placed in contact with a thermal block to regulate temperature of its contents. The metal foil also includes openings that form ports of various channels and reservoirs that can interface with ports on a moveable radial valve assembly. The metal foil also includes openings for tension assembly clips, radial valve drive interface, and radial valve position detection windows. [00103] Figure 9A is a diagram illustrating an embodiment of a radial valve assembly. In various embodiments, radial valve assembly 902 is an example of radial valve assembly 832 of Figure 8B. In various embodiments, radial valve assembly 902 includes at portions of radial valve 506 of Figure 5, 606 of Figure 6 and/or 706 of Figures 7A-7D. Radial valve assembly 902 may be included in a cartridge (e.g., cartridge 802 is cartridge 502 of Figure 5, cartridge 602 of Figure 6 and/or cartridge 702 of Figures 7A-7D).

[00104] Radial valve assembly 902 has been molded to include channel 904 and channel 906. For example, radial valve assembly 902 is made of injection molded bio compatible polypropylene and channel 904 and channel 906 are molded grooves on radial valve assembly 902. In some embodiments, channel 904 corresponds to channel 722 of Figures 7A-7D and channel 906 corresponds to channel 723 of Figures 7A-7D.

[00105] Radial valve assembly 902 includes gear teeth around a bottom rim

(shown in Figures 9B-9E) of the radial valve assembly 902 of the radial valve (e.g., teeth shown in radial valve assembly 832 of Figure 8B that engage with teeth of drive gear 821 of Figure 8B). A drive gear engages with the teeth of radial valve assembly 902 to rotate the radial valve assembly 902. In some embodiments, the drive gear is driven by an actuator that couples with the drive gear via an end effector that mechanically engages with a mechanical engagement interface of the drive gear. [00106] Radial valve assembly 902 includes home position alignment opening 924 and slot openings around an exterior rim of radial valve assembly 902. These openings are utilized to detect a rotational orientation of radial valve assembly 902 in a cartridge. For example, only when home position alignment opening 924 aligns with window 841 of Figure 8D is light able to pass through the cartridge via opening 924 and by detecting the rotational position when light emitted on top of the cartridge is detected by a sensor on instrument 840 through a corresponding window on the cartridge (e.g., corresponding window on bottom of cartridge), a reference home position is detected. In some embodiments, when a cartridge is first loaded on to an instrument, the actuator engages with a drive gear to rotate the radial valve assembly 902 until the reference home position is detected. The cartridge includes a second window corresponding to the slot opening around an exterior rim of radial valve assembly 902. Each slot/notch opening around the exterior rim of radial valve assembly 902 corresponds to a radial valve selection position. For example, when one of the slot openings is aligned with window 842 of Figure 8D, light is able to pass through the cartridge via window 842 and the rim slot opening, and by detecting when light emitted on to the top of the cartridge is detected by a sensor on instrument 840 through a corresponding window on the cartridge (e.g., corresponding window on bottom of cartridge), it is detected that radial valve assembly 902 has been rotated and aligned to one of the selectable positions of the radial valve. In some embodiments, once radial valve assembly 902 is placed into a reference home position, a current state of a selected position of the radial valve is maintained. For example, by counting the number of times light has been detected via one of the rim slot openings as radial valve assembly 902 is rotated, the current rotational location of the radial valve is tracked. [00107] A top view of radial valve assembly 902 is shown in Figure 9A.

When assembled in a cartridge, radial valve assembly 902 is covered with a cover material to seal channels 904 and 906. For example, a film or foil (e.g., heat sealed foil) is attached to the shown top of radial valve assembly 902 to cover the grooves of channels 904 and 906 to form enclosed channels. The cover material covering radial valve assembly 902 includes holes to match openings and slots of radial valve assembly 902 as well as create ports on channel 904 and 906. When the cover material with the openings is attached to radial valve assembly 902, the cover material includes an alignment opening that is matched with the shown assembly alignment hole 928 on radial valve assembly 902 to properly orient the cover material to the shown radial valve assembly 902.

[00108] Radial valve assembly 902 includes a set of ports on a top surface of radial valve assembly 902 and another set of ports on a bottom surface of radial valve assembly 902. As the radial valve assembly 902 is rotated into different selectable rotational positions, each position of the selectable positions corresponds to a different configuration of connection(s) and disconnection(s) between the port(s) of radial valve assembly 902 to selectable fixed ports above and below radial valve assembly 902. The ports on the top side of the radial valve assembly 902 selectively connect to ports on manifold assembly 831. For example, the top ports connect to ports of reagent reservoirs, crossover channels, solvent reservoir air vents, waste container, etc. A central port on the top side of the radial valve assembly 902 is always connected to the pump channel. These top ports of radial valve assembly 902 may be configured as holes on the cover material to provide access to channel 904 or 906 and correspond to holes located at locations corresponding to 908, 910, 918, and 926.

[00109] The ports on the bottom side of the radial valve assembly 902 selectively connect to input and output ports of a biochip. The holes corresponding to these bottom ports include holes 912, 914, 916, 920 and 922. Holes 914 and 922 (e.g., one of the holes acting as channel 724 of Figures 7A-7D) go through both radial valve assembly 902 and the cover material to act as a passage through radial valve assembly 902 to connect a biochip port below radial valve assembly 902 to a waste port above radial valve assembly 902. When port 916 is connected to an inlet port of a biochip, the outlet port is sealed and contents in channel 904 is able to be delivered to the chip and pressurizes the chamber of the biochip (e.g., helps push fluid into micro valves of the chip). When port 912 is connected to an inlet port of a biochip, the outlet port of the biochip is connected to port 914 (e.g., connected to waste) and content in channel 904 is able to be delivered to the chip in a non- pressurized manner as content in the chamber of the biochip exits via port 914. In some cases, rather than delivering content via an inlet port of a biochip, content is delivered via an outlet port of the biochip to avoid contamination of materials (e.g., between aqueous and non-aqueous materials). When port 920 is connected to an outlet port of a biochip, the inlet port of the biochip is connected to port 922 (e.g., connected to waste) and content in channel 906 is able to be delivered to the chip in a non-pressurized manner via port 920 as content in the chamber of the biochip exits via port 922.

[00110] Channel 904 and channel 906 are utilized to store and deliver content via ports on the respective channels. For example, a syringe pump is in communication with the central port of 906 and when the syringe pump applies vacuum/negative pressure to draw contents, channel 904 is filled with contents from a reservoir port connected to the port of 910. Then at another selectable position of the radial valve, the syringe pump applies positive pressure to expel contents and content in channel 904 is delivered via port 912 or 916 to the biochip. [00111] Thus channel 904 is able to be utilized as an intermediary container to hold various reagents and gases that are drawn from various reservoirs selected in various selectable positions of radial valve assembly 902 to be delivered to a biochip in other selectable positions of the radial valve assembly. However, certain reagents, gases, or solvents may contaminate other reagents, gases, or solvents and it is desirable to not utilize the same channel for certain reagents, gases, or solvents with certain other reagents, gases, or solvents. For example, aqueous materials are not to be contaminated by non-aqueous materials and channel 904 is to be utilized to hold aqueous materials while channel 906 is to be utilized to hold non-aqueous materials. Channel 906 is not directly connected to central port 926 and only when contents are to be drawn into (via port of 918) or delivered (via port 920) from channel 906, channel 906 is connected to the pump via channel 904 and central port of 926. This connection between channel 904 and 906 is achieved via a crossover channel (e.g., shown in Figure 8D) that connects the ports of 908 and 910 in certain selectable positions of the rotatory valve. [00112] Figures 9B-9E are diagrams illustrating embodiments of a radial valve cartridge drawing and delivering content in various selectable radial valve positions. In various embodiments, radial valve assembly 902 is an example of radial valve assembly 832 of Figure 8B. In various embodiments, radial valve assembly 902 includes at portions of radial valve 506 of Figure 5, 606 of Figure 6 and/or 706 of Figures 7A-7D. Cartridge 900 is an example of cartridge 802 of

Figure 8A, cartridge 502 of Figure 5, cartridge 602 of Figure 6 and/or cartridge 702 of Figures 7A-7D. Components of cartridge 900 are shown in a see-through view to illustrate the fluid communication pathways that have been highlighted in Figures 9B-9E. [00113] In Figure 9B, radial valve assembly 902 has been rotated to a selectable radial valve position that positions port of 910 on a selectable port of a reagent reservoir. A pump in communication with central port of 926 applies negative pressure to draw contents of the reagent reservoir into channel 904 via port of 910. After drawing the reagent into channel 904 in Figure 9B, Figure 9C shows radial valve assembly 902 has been rotated to another selectable position to position port 912 to an input port of biochip 930 to deliver the reagent to biochip

930 (e.g., pump applies positive pressure). Port 914 has been positioned over the exit port of biochip 930. In various embodiments, biochip 930 is biochip 504 of Figure 5, biochip 604 of Figure 6, biochip 704 of Figures 7A-7D, and/or biochip 836 of Figure 8B. As shown in Figures 9B and 9C, channel 904 is to be utilized to hold and deliver only aqueous content.

[00114] In Figure 9D, radial valve assembly 902 has been rotated to a selectable radial valve position that positions port of 940 on a selectable port of a lipid solvent reservoir. A pump in communication with central port of 926 applies negative pressure to draw contents of the lipid solvent reservoir into channel 906. Because channel 904 is to be utilized to hold and deliver only aqueous content, channel 906 is to be utilized to hold and deliver only non-aqueous content. Channel 906 has been connected to channel 904 to be in communication with the pump to access the power of the pump. Channel 906 is connected to channel 904 via the fixed crossover channel 932 connected via ports of 908 and 910. After drawing the lipid solvent into channel 904 in Figure 9D, Figure 9E shows that radial valve assembly 902 has been rotated to another selectable radial valve position to position port 920 to an output port of biochip 930 to deliver the lipid solvent to biochip 930 (e.g., pump applies positive pressure). Port 922 has been positioned over the exit port of biochip 930. In this new selectable position, a different crossover channel 934 is utilized to connect channel 906 with channel 904 via ports of 908 and 910.

[00115] By using different channels on the radial valve assembly and different ports of the biochip to delivery content for aqueous content vs. nonaqueous content, contamination between aqueous vs non-aqueous content is eliminated. This may allow the same cartridge to be utilized again to repeat measurements and assays (e.g., for the same sample) multiple times. [00116] Figures 10A-10G are diagrams illustrating embodiments of an end effector. The end effector shown in Figures 10A-10G may be end effector 850 of Figure 8C that is utilized to drive a radial valve of cartridge 802. The embodiments shown in Figures 10A-10G are merely examples, and various select features of the shown examples may be utilized and combined with other features in other embodiments. Figure 10A shows an external view of an end effector. Figure 10B shows components that are included in an end effector. Figure IOC shows a cutaway internal view of an end effector at rest.

[00117] In some embodiments, an end effector coupled to an actuator engages a mechanical engagement interface (e.g., on 812 of Figure 8 A) to select a desired selectable position/port. An end component of the end effector is configured to independently move with at least one degree of freedom relative to a shaft component of the end effector. For example, the end component is an end cap component that is coupled over an end of the shaft component with a pin joint, and the end component rides along tapered sides of the shaft to provide limited side tilt degree of movement. The end component may be configured to contract and expand (e.g., move up and down) in the direction of a length of the shaft with respect to the shaft component. Although the end component is configured to independently move with at least one degree of freedom relative to the shaft component to tolerate misalignment with the mechanical engagement interface of the selectable valve, the end component is not allowed a rotational degree of freedom (e.g., end component is rotationally fixed to the shaft component about the rotational axis of the shaft component). This allows a torque applied on the shaft component to be transmitted to the end component to allow the end component to rotate the mechanical engagement interface of the selectable valve. A tip of the end component includes a feature configured to engage with the mechanical engagement interface of a selectable valve and rotate the mechanical engagement interface to select a desired position/port of the selectable valve (e.g., selectable valve 606 of Figure 6, selectable valve 706, etc.). For example, the mechanical engagement interface is on the cartridge that is removable from an instrument system that includes the end effector and by allowing the end component one or more degrees of freedom movement relative to the shaft component, variances in location of the end effector with respect to the mechanical engagement interface due to manufacturing/assembly variances/tolerances and/or cartridge positioning variances are able to be tolerated. Figures 10A-10G show embodiments of the end effector. [00118] End effector 1000 includes shaft component 1002 and end component 1004. End effector 1000 may be coupled/attached to an actuator/motor (e.g., motor 718) that turns/spins end effector 1000 (about its central axis that goes down in the length of end effector 1000) to spin tip features 1014 and 1016 that can mechanically couple (e.g., clip into, slip fits, etc.) with a mechanical engagement interface (e.g., 812 of Figure 8A) of a selectable valve included in a cartridge (e.g., cartridge 502 of Figure 5, 602 of Figure 6, 702 of Figures 7A-7D, 802 of Figures 8A-8C, or 900 of Figures 9B-9E). End component 1004 is coupled to shaft component 1002 via pin 1006 to form a pin joint to allow end component 1004 to move independent of shaft component 1002. End component 1004 includes a hollow barrel with an opening forming a collar where an end of shaft component

1002 is inserted and coupled. Shaft component 1002 is coupled/attached to an actuator shaft (or an extension shaft coupled to the actuator shaft) via screws 1012 that fix the actuator shaft (or the extension shaft) within a cavity of shaft component 1002. As shown in the figures, sharp edges have been beveled. [00119] Spring 1008 is placed within the hollow barrel of end component

1004 and spring 1008 presses against a closed end of the hollow barrel of end component 1004 and a tip end of shaft component 1002. The tension of spring 1008 extends end component 1004 from shaft component 1002 while allowing end component 1004 to be pressed towards shaft component 1002 when spring 1008 is collapsed due to an external force applied against end component 1004. When pin

1006 (e.g., acting as a spring pin) is inserted in shaft component 1002, ends of pin 1006 extend out from sides of shaft component 1002 and catches on opening 1010 of end component 1004. Opening 1010 is larger than a diameter of pin 1006 in at least one direction to allow end component 1004 to independently move from shaft component 1002. As shown in Figures 10A-10G, opening 1010 allows end component 1004 to move up and down independently with respect to shaft component 1002 but does not allow it to move independently in the rotational direction of end effector 1000. The tension of spring 1008 forces an end of pin 1006 to catch at one end of opening 1010 corresponding to an extended position of end component 1004 when no external force is applied on end component 1004. As external force is applied (e.g., by a mechanical engagement interface), spring 1008 is collapsed and an end of pin 1006 travels within opening 1010 from one end towards the other end (e.g., shown in the figures at top end) of opening 1010 corresponding to a collapsed limit.

[00120] In an alternative embodiment, internal spring 1008 is not utilized. For example, allowing an internal spring to apply force back towards shaft component 1002 that is coupled to a motor strains the motor due to the thrust force applied on the motor by the spring and internal spring 1008 is not utilized to reduce this thrust force. In some embodiments, end component 1004 is configured to not move up and down independent of shaft component 1002. In some embodiments, end component 1004 is configured to move up and down independent of shaft component 1002 without a spring that applies force against shaft component 1002 (e.g., internal spring 1008 is removed). For example, a different spring embodiment (e.g., external spring that is external to end component 1004) that applies extension force to end component 1004 against an external support is utilized. This external support does not rotate when end effector 1000 is rotated and Teflon or other low friction materials may be utilized to minimize friction between the spring and the external support or end effector.

[00121] A tip of end component 1004 includes features 1014 and 1016 that mechanically couple (e.g., slip fit) with a mechanical engagement interface (e.g., 812 of Figure 8A) of a selectable valve. For example, these features are press/slip fitted into a corresponding opening on the mechanical engagement interface of a rotatory valve cartridge and a force applied against the mechanical engagement interface retains the coupling between end component 1004 and the mechanical engagement interface. Rotation of end component 1004 by an actuator also causes the mechanical engagement interface to rotate together with the coupled end component 1004. [00122] The tip features include center feature 1014 and paddle feature

1016. Center feature 1014 extends beyond/above paddle feature 1016 and allows end component 1004 to be centered on the mechanical engagement interface that has a corresponding mating cavity centered in mechanical engagement interface and shaped to accept center feature 1014. Paddle feature 1016 allows a rotational force on end component 1004 by a coupled actuator to be applied against a radial length paddle feature 1016. Paddle feature 1016 is also press/slip fitted into a corresponding mating cavity shaped to accept paddle feature 1016.

[00123] In some embodiments, end component 1004 is made of a lubricous metal (e.g., brass) to facilitate easier insertion of the tip of end component 1004 into the mechanical engagement interface. In some embodiments, shaft component 1002 is made at least in part of stainless steel. Center feature 1014 may be made of a different type of material than paddle feature 1016 (e.g., for ease of

manufacturing, for functional advantages, etc.). For example, when a metal block is machined to fabricate end component 1004, a cylindrical cavity is left where a cylindrical rod that is to form center feature 1014 is inserted. Center feature 1014 may be made of stainless steel due its ready-made availability and/or its properties (e.g., less lubricous metal) as compared to the material of paddle feature 1016. In some embodiments, center feature 1014 and paddle feature 1016 are made of the same material.

[00124] In some embodiments, the mechanical engagement interface (e.g.,

812 of Figure 8A) where the tip of end component 1004 (e.g., including features 1014 and/or 1016) is to be coupled and/or at least a portion of the tip of end component 1004 (e.g., including features 1014 and/or 1016) is functionalized to increase adhesion. For example, the mechanical engagement interface and/or features 1014 and 1016 are coated with a gel-based adhesive to increase adhesion between the mechanical engagement interface and the tip of end component 1004.

[00125] End component 1004 includes a hollow cylindrical barrel that allows an end of shaft component 1002 to fit inside the hollow cylindrical barrel and move in and out of the hollow cylindrical barrel to contract or expand the length of end effector 1000. As shown in the figures, the walls of the cylindrical barrel are smooth and at least a portion of shaft component 1002 configured to fit inside the hollow cylindrical barrel of end component 1004 is tapered. For example, shaft component 1002 tapers in two directions away from a central circumference on the portion of shaft component 1002 configured to fit inside the hollow cylindrical barrel of end component 1004. The hole where pin 1006 is inserted goes through this central circumference. These two directional tapers allow end component 1004 to tilt/wiggle sideways in any direction around the

circumference of shaft component 1002 as the straight sidewalls of the hollow cylindrical barrel of end component 1004 ride on the tapered sides of shaft component 1002. The amount of allowed tilt with respect to shaft component 1002 corresponds to the degree of tapers of shaft component 1002. The tilt (e.g., a first degree of freedom) as well as the compression/expansion (e.g., a second degree of freedom) of the end effector allow it to move and accommodate for variances in the location of the mechanical engagement interface due to manufacturing/assembly tolerances/variances and/or cartridge positioning variances. However, end component 1004 is not allowed to freely rotate about the rotational axis of shaft component 1002 (e.g., in the plane perpendicular to the length of shaft component 1002 and in the plane of the circumference of shaft component 1002). For example, end component is rotationally fixed to the shaft component via pin 1006. This allows a torque applied on the shaft component to be transmitted to the end component to allow the end component to rotate the mechanical engagement interface of the selectable valve.

[00126] Figure 10D shows an end effector that has been tilted at its limit of two degrees (e.g., slope of both tapers on shaft component 1002 is also two degrees). The limit of two degrees is merely an example. In other embodiments, the end component of the end effector may be tilted a more or less number of degrees. Figure 10D demonstrates a degree of freedom of movement of end component 1004 with respect to shaft component 1002. Figure 10E shows a cutaway view of the tilted end effector shown in Figure 10D. As shown in Figure 10E, the sidewalls of the hollow cylindrical barrel of end component 1004 are touching the tapered sides of shaft component 1002. [00127] Figure 10F shows an end effector that has been both tilted and compressed/pushed down at its maximum limit. Figure 10F demonstrates two different degrees (e.g., tilt and compression) of freedom of movement of end component 1004 with respect to shaft component 1002. Figure 10G shows a cutaway view of the tilted and compressed/pushed down end effector shown in

Figure 10F. As shown in Figure 10G, the sidewalls of the hollow cylindrical barrel of end component 1004 are touching the tapered sides of shaft component 1002 and end component 1004 has been pushed down to its limits on the portion of shaft component 1002 configured to fit inside the hollow barrel of end component 1004 as well as the limit reached by pin 1006 in opening 1010.

[00128] In some embodiments, end effector 1000 is coupled to an actuator and included together in assembly (e.g., assembly with actuator shown in Figure 8C) that moved together as the assembly unit (e.g., lowered) to engage a cartridge (e.g., cartridge 502 of Figure 5, 602 of Figure 6, 702 of Figures 7A-7D, 802 of Figures 8A-8C or 900 of Figures 9B-9E) in an instrument system. When the cartridge is to be removed/replaced, the assembly unit with the end effector can be moved (e.g., raised) to decouple the end effector from the interface of the cartridge. In an alternative embodiment, end effector 1000 engages a cartridge from an interface on a bottom of the cartridge and the cartridge is lowered on to the end effector mounted on an instrument pointing upwards from a lower base. When the cartridge is to be removed/replaced in this embodiment, the cartridge is able to be lifted out of the instrument to decouple the interface of the cartridge from the end effector.

[00129] The cartridge includes a selectable valve selected via a rotation of the mechanical engagement interface by a tip of the end component of the end effector. In some embodiments, when the end effector contacts the mechanical engagement interface, a homing routine is performed to engage the end effector to the mechanical engagement interface and initialize positioning of a selectable valve. By utilizing the homing routine, the tip of the end component of end effector 1000 is able to engage the mechanical engagement interface in a plurality of different orientations/positions rather than only at a single position/orientation. For example, the tip of end effector 1000 is symmetrical along multiple axes to allow the tip of end effector 1000 to engage a corresponding mating cavity faster in a variety of rotational orientations/positions rather than only allowing the tip of end effector 1000 to engage the mating cavity at a single rotational orientation/position with respect to each other.

[00130] Additionally, the position/orientation of the mechanical engagement interface does not necessarily correspond with a certain selectable valve position of the selectable valve in the cartridge. For example, if the position/orientation of the mechanical engagement interface necessarily corresponds to a certain selectable valve position, the cartridge would have to be assembled and manufactured in a manner that requires careful calibration and assembly procedure to match specific absolute position/orientation of the mechanical engagement interface to specific selectable valve positions. This can be error prone and costly. Rather, the homing routine is utilized to confirm engagement of the mechanical engagement interface and place the selectable valve in a known default position.

[00131] In some embodiments, performing the homing routine includes positioning the end effector on to the mechanical engagement interface of the selectable valve cartridge, (e.g., lower the assembly including the end effector coupled to an actuator down to the mechanical engagement interface) and rotating the end effector until a home position on the selectable valve is detected by a sensor (e.g., optical break beam sensor). When the end effector first contacts the mechanical engagement interface, the tip of the end effector may not have fully engaged the mating cavity/port on the mechanical engagement interface. This forces the end component of the end effector to become compressed, which compresses the internal spring of the end effector and forces the tip of the end effector to apply a spring force against the mechanical engagement interface. As the end effector is rotated in the homing routine, the end effector expands when the tip of the end effector is in rotational ordination/position to engage the mating cavity/port of the mechanical engagement interface due to the force of the internal spring releasing against the end component of the end effector to drive the tip into the mating cavity of the mechanical engagement interface. This forms a press/slip fit mechanical connection between the mechanical engagement interface and the end effector. The spring has enough force in its expanded position to keep the end effector engaged in the mating cavity/port while the tip of the end effector turns the mechanical engagement interface via the turning force applied by the tip features in the mating cavity of the mechanical engagement interface.

[00132] In some embodiments, the mechanical engagement interface

(including the mating cavity) has been produced using an injection molding process that requires the sidewalls of the mating cavity of the mechanical engagement interface to slope outward (e.g., to allow a mould to be more easily removed). In some embodiments, rather than allowing the slope of sidewalls of tip features (e.g., features 1014 and 1016) of the end effector to match the slope of sidewalls of the mating cavity of the mechanical engagement interface, the sidewalls of the tip features of the end effector are configured to have a slope that is more steep (e.g., vertical with no slope) than the slope of sidewalls of the mating cavity (e.g., sidewalls of tip features are do not touch the sidewalls of the mating cavity when tip is slip fitted in the mating cavity). This allows force of the internal spring to be concentrated on the corners/edges of the tip features on a smaller surface area to allow it to dig into the mating cavity and provide a stronger mechanical connection with the end effector of the mechanical engagement interface. If the slope of sidewalls of the tip features matches the slope of the sidewall of the mechanical cavity/port, the force applied by the spring becomes distributed over a greater area and may cause the tip of the end effector to become dislodged from the mechanical cavity/port (e.g., cam-out) while the end effector is rotated.

[00133] In some embodiments, the rotation of the engagement interface is on a gear component that turns gears on a radial valve. As the radial valve is rotated, one or more optical openings/patterns on an assembly of the radial valve are also rotated. As the end effector is rotated during the homing routine, the radial valve is placed in a known default home position by detecting the optical opening/pattern that corresponds to the home position. For example, when opening 924 of Figure 9A is viewable via window 841 shown in Figure 8D, the home position of the radial valve is detected (e.g., using an optical break beam sensor) and utilized as a reference position (e.g., subsequent radial selectable valve positions detected with respect to the detected home position via optical openings/patterns on the edge of assembly 902 of Figure 9A detected via window 842 shown in Figure 8D).

[00134] Figure 11 is a flowchart illustrating an embodiment of a process for flowing different types of materials (e.g., liquids or gases) through the cells of a nanopore-based sequencing biochip during different phases of the biochip operation. The nanopore-based sequencing biochip operates in different phases, including an initialization and calibration phase (phase 1102), a membrane formation phase (phase 1104), a nanopore formation phase (phase 1106), a sequencing phase (phase 1108), and a cleaning and reset phase (phase 1110). In some embodiments, the biochip of Figure 11 includes cell 100 of Figure 1. In some embodiments, the biochip of Figure 11 is biochip 504 of Figure 5. In some embodiments, the biochip of Figure 11 is biochip 604 of Figure 6. In some embodiments, the biochip of Figure 11 is biochip 704 of Figures 7A-7D. In some embodiments, the biochip of Figure 11 is biochip 836 of Figure 8B. In some embodiments, the biochip of Figure 11 is biochip 930 of Figures 9B-9E. In various embodiments, the process of Figure 11 is at least in part performed using cartridge 502 of Figure 5, 602 of Figure 6, 702 of Figures 7A-7D, 802 of Figures 8A-8C or 900 of Figures 9B-9E. [00135] At the initialization and calibration phase 1102, a salt buffer solution is flowed through the cells of the nanopore-based sequencing chip at 1112. The salt buffer solution may be potassium choloride (KC1), potassium acetate (KAc), sodium trifluoroacetate (NaTFA), and the like. In some embodiments, performing step 1112 using cartridge 602 of Figure 6 includes using actuator/motor 618 to rotate radial valve 606 to select port 627, drawing the salt buffer solution into syringe pump chamber 632 using motor 630, using motor 618 to rotate radial valve 606 to select port 621, and pushing out the salt buffer solution in pump chamber 632 to the chamber of biochip 604 via selected port 621. In some embodiments, salt buffer solution is flowed through the cells via pump 730 by rotating radial valve 606 to select port 733 of Figures 7A-7D. In some embodiments, when a cartridge (e.g., cartridge 502 or Figure 5, cartridge 602 of Figure 6, 702 of Figures 7A-7D, etc.) is utilized in performing the process of Figure 11, the cartridge is primed for initial use. For example, various materials connected to selectable ports of a selectable valve are primed to draw materials through channels to the selectable ports for use during the process. Excess materials drawn during priming may be discarded to a waste container (e.g., waste 638 via bypass channel 654 of

Figure 6).

[00136] At the membrane formation phase 1104, a membrane, such as a lipid bilayer, is formed over each of the cells. At 1114, a lipid and solvent mixture is flowed over the cells. In some embodiments, flowing the lipid and solvent mixture includes flowing an air buffer (e.g., air bubble) prior to and after flowing the lipid and solvent mixture. Using the example of Figure 6 to perform step 1114, actuator/motor 618 is used to rotate radial valve 606 to select port 628, air from vent of selectable port 628 is drawn into pump chamber 632 using pump motor 630, motor 618 is used to rotate radial valve 606 to select port 624, a lipid and solvent mixture is drawn into chamber 632, motor 618 is used to rotate radial valve

606 to select port 628, air is again drawn into pump chamber 632 using pump motor 630, motor 618 is used to rotate radial valve 606 to select port 621, and then the combination of air buffer, mixture, and another air buffer in pump chamber 632 is pushed to the chamber of biochip 604 via selected port 621. As material is flowed over the biochip, the materials that have already flowed across the biochip are pushed into a waste container after exiting the chamber of the biochip. Using the example of Figures 7A-7D to perform step 1114, actuator/motor 718 is used to rotate radial valve 706 to select the lipid solvent reservoir port; a lipid and solvent mixture is drawn into channel 723; and motor 718 is used to rotate radial valve 706 to select port 735; and then the lipid solvent is pushed to the chamber of biochip

704 via selected port 735.

[00137] At 1116, a salt buffer solution is flowed over the cells. In an example utilizing a selectable valve, a particular selectable port connected to a salt buffer solution container is selected to draw the salt buffer solution into a pump chamber and pushed into the chamber of the biochip.

[00138] At 1118, voltage measurements across the lipid bilayers are made to determine whether the lipid bilayers are properly formed. If it is determined that the lipid bilayers are not properly formed, then step 1116 is repeated; otherwise, the process proceeds to step 1120. At 1120, a salt buffer solution is again introduced. For example, a previously described selectable valve is utilized to draw and push the salt buffer to biochip 604/704.

[00139] At the nanopore formation phase 1106, a nanopore is formed in the bilayer over each of the cells. At 1122, a sample and a pore/polymerase mixture are flowed over the cells. In some embodiments, performing step 1122 using cartridge 602 of Figure 6 includes using actuator/motor 618 to rotate radial valve 606 to select port 623, drawing a sample and pore/polymerase mixture into pump chamber 632, using motor 618 to rotate radial valve 606 to select port 621, and pushing out the mixture in pump chamber 632 to the chamber of biochip 604 via selected port 621. In some embodiments, performing step 1122 using cartridge 702 of Figures 7A-7D includes using actuator/motor 718 to rotate radial valve 706 to select port of reservoir 710, drawing a sample and pore/polymerase mixture into channel 722, using motor 718 to rotate radial valve 706 to select port 733, and pushing out the mixture in channel 722 to the chamber of biochip 704 via selected port 733.

[00140] In order to not disturb the bilayer that has been formed in phase 1104, an air buffer is not introduced between the ending salt buffer solution of

1120 and the sample and pore/polymerase mixture of 1122. In some embodiments, rather than disturbing the nanopore that has been formed by allowing the sample and pore/polymerase mixture to flow completely across the chamber of a biochip and into a waste container, the mixture is pulled from the chamber of the biochip from the chamber opening where the mixture was introduced and the pulled mixture is discarded via a bypass port/channel that does not traverse the chamber of the biochip. For example, using cartridge 602 of Figure 6, radial valve 606 is configured to select port 621, the sample and pore/polymerase mixture in the chamber of biochip 604 is drawn into pump chamber 632, radial valve 606 is actuated to select port 660 (e.g., in the embodiment of Figure 6 where bypass channel 654 is directly connected to radial valve 606 via port 660 and valve 650 is replaced with a direct connection between port 621 and the chamber of biochip 604), and the contents of pump chamber 632 is discarded to waste container 638 via bypass channel 654 without flowing through chamber port 651.

[00141] At sequencing phase 1108, a biological assay (e.g., DNA

sequencing) is performed. At 1124, StartMix is flowed over the cells, and the sequencing information is collected and stored. StartMix is a reagent that initiates the sequencing process. In some embodiments, performing step 1124 using cartridge 602 of Figure 6 includes using actuator/motor 618 to rotate radial valve 606 to select port 622, drawing StartMix into syringe pump chamber 632, using motor 618 to rotate radial valve 606 to select port 621 , and pushing out the

StartMix in pump chamber 632 to biochip 604 via selected port 621. In order to not disturb the bilayer and nanopore that has been formed, an air buffer is not introduced before the StartMix. After the sequencing phase, one cycle of the process is completed at 1126. In some embodiments, performing step 1124 using cartridge 702 of Figures 7A-7D includes using actuator/motor 718 to rotate radial valve 706 to select the port of reservoir 712, drawing StartMix into channel 722, using motor 718 to rotate radial valve 706 to select port 733 and pushing out the StartMix in channel 722 to biochip 704 via selected port 733. In order to not disturb the bilayer and nanopore that has been formed, an air buffer is not introduced before the StartMix. After the sequencing phase, one cycle of the process is completed at 1126.

[00142] At the cleaning and reset phase 1110, the nanopore-based sequencing biochip is cleaned and reset such that the chip can be recycled for additional uses. For example, a biological assay (e.g., DNA sequencing) of the same sample is performed again. At 1128, a surfactant is flowed over the cells. At

1130, a cleaning solution is flowed over the cells. Although a surfactant and the cleaning solution are used for cleaning the chip in this embodiment, alternative fluids may be used in other embodiments. Steps 1128 and 1130 may also be repeated a plurality of times to ensure that the chip is properly cleaned. In various embodiments, one or more cleaning fluids are obtained via one or more selectable ports of a selectable valve (e.g., radial valve 606 of Figure 6) to be pushed and fiowed over the biochip to be cleaned. After step 1130, the lipid bilayers and pores have been removed and the fluidic workflow process 1100 can be repeated at the initialization and calibration phase 1102 again.

[00143] As shown in process 1100 described above, multiple materials with significantly different properties (e.g., compressibility, hydrophobicity, and viscosity) are flowed over an array of sensors on the surface of the nanopore -based sequencing biochip. For improved efficiency, each of the sensors in the array should be exposed to the fluids or gases in a consistent manner. For example, each of the different types of fluids should be flowed over the nanopore-based sequencing chip such that the fluid or gas may be delivered to the chip, evenly coating and contacting all of the cells' surface, and then delivered out of the chip. As described above, a nanopore-based sequencing biochip incorporates a large number of sensor cells configured as an array. As the nanopore-based sequencing chip is scaled to include more and more cells, achieving an even flow of the different types of fluids or gases across the cells of the chip becomes more challenging. Although examples related to Figure 6 have been discussed in conjunction with the process of Figure 11, in various embodiments, other selectable ports and cartridges (e.g., using the the components of the examples of Figures 5, 7A-7D, 8A-8E, 9A-9E, etc.) may be utilzed to implement the process of Figure 11. [00144] Although the foregoing embodiments have been described in some detail for purposes of clarity of understanding, the invention is not limited to the details provided. There are many alternative ways of implementing the invention. The disclosed embodiments are illustrative and not restrictive.

[00145] All publications, patents, patent applications, and/or other documents cited in this application are incorporated by reference in their entirety for all purposes to the same extent as if each individual publication, patent, patent application, and/or other document were individually indicated to be incorporated by reference for all purposes.