Background to the invention Microfluidic connectors are required for external connection to a reservoir, interconnecting two microfluidic devices by tubing or interconnecting modular parts by using a fluidic bus. Connections are required between microfluidic wafers and between fixed and disposable devices from micro to macro connections for single and multi channel devices. The results obtained by research groups are still not meeting all the requirements for these targets.

The design of fluidic interconnects is influenced by the intended application of the device the types of manipulations on fluids to be performed and the performance criteria.

The ideal interconnect design is one that has the least possible effect on fluid flow.

The performance criteria can be split into different elements: Dead volume; (Influence carryover and metering precision) Reversibility ; (Cost of servicing and flexibility of system) Leak rate; (Loss of fluid and entrance of bubbles) Maximum pressure; (High pressures need robust design of the connector) Change of cross-section; (Influences degassing due to sudden pressure drops and carryover) Maximum temperature; (Choice of materials for connector/device) Compatibility of materials. (Influences reliability of sample and carryover) These criteria need to be evaluated in relation to the amount of fluid that the device handles. For example, a nanoliter of dead volume is insignificant in devices handling milliliters of fluid, but can be catastrophic in a miniaturised device handling only nanoliters of fluid. Also, the need for a change of cross-section will almost be inevitable for components having channel dimensions of the order of 100 pm.

USA patent 6319476 discloses a connector that urges the tube and a seal against the microfluidic device. The clamping member is a screw threaded adaptor holding the tube. This device is reconnectable.

USA patent 6209928 uses a screw threaded arrangement to provide a reconnectable connector while patent 6273478 covers simpler arrangements. Both patents disclose arrangements in which the tube tips to be inserted need to be micromachined to have a narrower tip with projections or recesses.

W001/86155 discloses an adaptor facilitating microfluidic connections. The device has a large footprint and a relatively complicated rig without eliminating dead volume.

USA patent 6605472 discloses a method of connecting a capillary tube to a micro chip device by drilling into the edge of the micro chip to create a flat bottomed hole to communicate with the capillary channel. This enables the microchip device to be used with a mass spectrometer.

At present although there are many connectors that are available for sale and many that have been proposed there is no one fitting that has become an acceptable standard.

A commonly used tubing material in microfluidic connections is made of polyethylethyleneketone (PEEK).

It is an object of this invention to provide a connection device and method that meets the desirable criteria.

Brief description of the invention In a first aspect, the present invention provides a micro fluidic connection port in which a) a microfluidic channel is formed in one surface of a substrate b) a microfluidic through hole extends from the second face of the substrate into said microfluidic channel c) a larger diameter recess is formed about the through hole in the opposite face d) a support is bonded to the second surface about said recess e) said support having a through hole of diameter equal to the diameter of said recess f) the diameter of said recess and support through hole accommodating the external diameter of a connection tube for connecting the microfluidic device to an external device.

By selecting appropriate materials the following design conditions can be met using this construction: 1. Easy to connect/disconnect ; 2. Free of leakage up to 700kPa (= 7 bar); 3. Able to withstand pressures up to 700kPa (= 7 bar); 4. Reliable ; 5. fits flat surfaces; 6. Low dead volume (< 5% total volume device); 7. uses standard commercial available tubing (PEEK); 8. Compatible with fluids used in PCR; 9. Biocompatible materials ; 10. Small footprint in relation to device (<100mm2) ; 11. Reusable (minimal 10x connecting/disconnecting while still meeting conditions); 12. is able to resist temperatures up to 95 degrees Celsius ; 13. Connector does not have influence on minimal thickness device.

A sealant material is preferably included in the through hole of the support so that it seals around the end of the tube and the area around the microfluidic through hole.

In a second embodiment the present invention provides a connection assembly adapted to connect a tube to a micro fluidic channel which includes a) a connector base that consists of a tube recess adapted to receive the end of a connector tube b) the micro fluidic channel terminates in said recess c) a clamping recess at least partially surrounding said tube recess and spaced from said tube recess d) a connecting tube optionally incorporating a gasket on its end face which is adapted to seat in said tube recess e) a wedging clamp fitted to said tube which has an inclined face to the wall of the clamping recess so that the tube is fastened to the connector base by pressing down on the wedging clamp.

The advantage of this connector is that expensive micro machining of the tubes and the base are avoided and connection is achieved by pressing.

The tube is of PEEK and the microfluidic device is preferably formed of poly methylmethacrylate (PMMA). The gasket is preferably made of polydimethylsiloxane (PDMS).

Detailed description of invention Preferred embodiments of the invention will be described with reference to the drawings in which: Figure 1 is a schematic representation of a first embodiment of this invention; Figure 2 is a graph illustrating the pulling force required for the device of figure 1; Figure 3 is a schematic representation of a second embodiment of the invention; Figure 4 is a cross sectional view of the figure 3 embodiment for general use and; Figure 5 illustrates the details of the connector of figure 3 used for applications where dead volume is an issue.

This invention is based on the commonly used standard PEEK (polyethylethylene ketone) tube to connect a microfluidic device to supply the micro to macro connection. This invention provides a connector for microfluidic systems useful in the medical and biomedical field, that optimizes performance in terms of fluidic volume, dead volume, size, connection time and reliability.

The connector is made for a PEEK tube connecting to a microfluidic device.

In the embodiment shown in figure 1 it consists of a PEEK tube11, a wedge fitting 13, a gasket seal 15 and connector base 17. As shown in figure 1, a tube recess 12 is formed on the connector base 17 to leave a desired thickness of wall 14 on the outside of the recess 12. A circular clamping slot 16 of the same depth as the tube recess 12 is cut around the tube recess 12. The wedge fitting 13 is machined to a have an internal conical recess so that the rim 19 is of suitable dimensions to match the tube size, the depth of the clamp recess 16 and the diameter of the clamp recess 16. The angle of the internal cone 19 is determined by calculation to reach a suitable lock angle.

The assembly steps are a) push and hold down the PEEK tube

b) then push down the fitting.

The disconnection steps are a) lifting the fitting b) and then lifting the PEEK tube.

This connector has been designed to keep the liquid volume in the micro-scale with no dead volume in the design principle as the pressed gasket internal diameter is of the same size as the PEEK tube internal, diameter and the internal diameter of the microfluidic channel.

As many microfluidic devices are made of multi-layers polymer sheet, the connector base of this invention can be pre-formed on the microfluidic device directly if the microfluidic device has a sufficient free area and the required thickness. Otherwise, the connector base can be made as additional layer or base and bonded onto the microfluidic device.

The wedge fitting and connector base may be fabricated using PMMA (polymethylmethacrylate) or polycarbonate. The connector bases are machined by micro milling a 2 mm PMMA or polycarbonate sheet and the fittings are machined on a lathe machine. The PEEK tube is 1.6 mm outer diameter with 0.5 mm inner diameter. The gaskets were cut by AVIA laser on 0.15 mm thickness PDMS (polydimethylsiloxane).

The circular clamping slot may vary with the recess wall having a thickness of 0.2, 0.3 and 0.4 mm thickness and 0. 8-1. 5 mm depth with 1.6 mm diameter 0. 8- 1.5 mm deep tube recess and 0.5 mm diameter micro fluidic channel in the centre.

Three wedge fittings were machined to match the three tube recess wall thicknesses in the connector base. The cone angle of the wedge fitting was selected to be 5 degree as lock angle based testing results.

Different forces are needed for connection and disconnection depending on different wall thickness and depth. The forces are reasonable for personnel to apply in a laboratory environment. Connectors were assembled for liquid pressure testing by connecting the PEEK tube to a syringe pump with colour liquid while blocking other end of the connector. The pressure reached over 75 Psi without any leakage.

The Pulling force on PEEK tube was tested on a ZWICK testing machine. The fittings were pushed in by hand and then the PEEK tube was pulled by the

machine. Then the machine was set up for applying a pushing force to let the machine push fittings in. Forces of 20,30, 40, and 50 Newtons were used which are within the range of a hand pushing force. The pulling force tests were done by repeating on same connector and with different fittings. The pulling force on the tube was over 20 Newtons.

Fig. 2 is a graph illustrating the pulling testing force against distance.

From the above it can be seen that this invention provides a connection that meets the requirements for microfluidic systems and laboratory products. The connector size, fitting tolerance, PEEK tube surface and shape can be modified to suit various applications. The connector of this invention is functional at high pressure, has a better lock angle and bigger pulling force than comparable fitting systems. It was found in trials that the polycarbonate fitting performed better than the PMMA device. In polycarbonate the pulling force reached 40 newtons without moving and without the sealing gasket could withstand 1.64 MPa without leaking.

The polycarbonate fitting was easier to connect and disconnect and had a reuse ability of 20 times.

A second embodiment is illustrated in figures 3-5. The surface connector consists of 4 parts, as illustrated in figure 3. The base part 21 contains the holes 23 to align the standard PEEK tubing. A microchannel in the base connects these holes, or ports of the device. After machining the channel needs to be isolated by laminating a layer 22 to the bottom of the base part 21 containing the microchannel. The moulded connector 25 ensures a reliable and firm connection of the tubing with the ports in the base part 21. To prevent leakage, a rubbery sealing/gasket 26 is applied.

The dimensions of the microchannel 24 in the base part are dependent on the application of the device. A typical dimension would be 200pm x 250 pm. This cross-sectional area corresponds to an inner diameter of 250 um in the PEEK tubing to create a homogeneous flow. The standard outer diameter of this PEEK tubing is 1/16", thus the alignment holes 23 in the base need to have the same dimension to mate accurately.

The design of the connector 25, in figures 4 & 5 has a hole at the top for alignment of the PEEK tubing. A cylindrical shaped cut-away under the hole provides room for moulding the rubbery sealing 26. The bottom part of the connector has a 10 x

15 mm footprint. However the flange is not essential and the foot print can be reduced to the area of the cylindrical tubing part.

In figure 4 the connector acts as a generic connector. Dead volume is not an issue and the connector 25 functions as a clamp to hold the tubing 20 in place without leaking.

In figure 5 the device is adapted for applications where dead volume is to be avoided. The tubing 20 will align with the via that connects to a microfluidic channel 24. By carefully matching the inner diameter of the hole in the substrate with the outer diameter of the tubing, an accurate connection will be realised.

Furthermore the inner diameter of the tubing will align with the via of the microfluidic channel.

The hole at the top of the connector is 1.5 mm. A steel wire with a diameter of 1.5 mm is inserted into this hole, to protect it from clogging and more important, align the hole in the rubbery sealing that is moulded into the cut-away of the connector.

The material used for the sealing is polydimethylsiloxane (PDMS). This two compound silicon rubber was moulded into the connector and the heat cured in a 100 Celsius heated oven for six hours. After curing the steel wire is pulled out of the connector and the top hole was drilled to meet the outer diameter of the tubing.

The inner diameter of the moulded sealing is still 1.5 mm, giving the connector good sealing and clamping properties. A very important feature of the moulding procedure is the bubble left on top of the cut-away in the connector as shown in figure 5. This bubble shaped part of the sealing material will be compressed when the connector is attached to the device, providing a pre-loaded sealing between the polycarbonate device and the ABS connector. Also, the diameter of the sealing at that part of the connector will decrease slightly, so improved clamping and sealing properties is achieved between the connector and the PEEK tubing.

The final part in this embodiment is the lamination of the polycarbonate base part.

After excimer laser micromachining of the channels in polymer substrates, the devices are sealed using a PET/PE (polyethylene terephthalate/polyethylene) laminate.

With all the separate parts fabricated, the device can be assembled. After machining all the necessary features in the polycarbonate base part, it can be laminated. The connector and sealing part are integrated in one final part during

fabrication. The last assembly step is the most important one, namely the mating of the hole in the connector with the hole in the device and also, the leakage free bonding of the connector with a preload in the sealing.

To achieve an accurate alignment of the two holes, a piece of tubing is inserted into the connector, while the end is sticking out about 2 mm. Then adhesive 27 (Loctite 406) is applied on the connector 25 and the whole put on the device. The tubing sticking out of the connector will secure the alignment, while the connector is pushed firmly on the polycarbonate base part. After several seconds the adhesive 27 has enough bonding strength to resist the preload in the sealing and connector, and the tubing may be released from the connector so that the device is ready. Alternately a double sided adhesive ring 27 having a thickness of 200 um and may be applied on the footprint of the connector. To bond the connector to a microfluidic device, a protective layer can be peeled off to expose the adhesive.

The hole in the centre provides room for the sealing member in the connector In one embodiment this connector will have the sealing pre assembled and the double sided adhesive ring is applied to the connector. To use, the protective layer is peeled off to expose the adhesive and the connector can be bonded to the micro device. The alignment will be accomplished by fitting a tube into the connector. The tip of the tube will protrude from the side with the adhesive. One now can put the tip in the micro device until it touches the bottom with the channel.

By sliding the connector over the tube towards the device, an accurate alignment will be achieved. Once the connector reaches the surface of the device, the adhesive layer will secure the position of the connector.

In order to determine the maximum resistible pressure on the connectors in the prototypes and to check for leakages, the devices were pressurised by blocking one of the in/outlets while the other one was connected to a computer controlled syringe pump. A pressure sensor registered the pressure in the tubing between the pump and the microdevice. A computer was used to acquire the data generated by this sensor. The first test showed a pressure running off scale at the display without any leakages observed. After multiple tests and reconnections no leakage could be observed at the surface connector, proving the durability to be very high for this type of connector. After multiple tests and reconnections no leakage could

be observed at the surface connector, proving the durability to be very high for this type of connector.

Those skilled in the art will realise that variations and modifications are possible without departing from the essence of this invention.

From the above it can be seen that the present invention provides a reusable connection system for microfluidic devices that uses commonly used materials without expensive manufacturing steps.