DE19942760C1 - Connector used in microtechnology for chemical analysis, e.g. capillary electrophoresis, comprises a flexible pressure-resistant material and has receiving chambers and a connecting channel - Google Patents

Abstract

A connector, comprises a flexible pressure-resistant material and has receiving chambers (31, 32) and a connecting channel (21). The parameters of the receiving chambers are selected so that microfluid line inserted into each receiving chamber is maintained under radial pressure.

Description

The invention relates to a connector for at least two together microfluidic lines to be connected with at least two receiving chambers and with at least one connecting the receiving chambers Connecting channel, the receiving chambers to the connecting channel border over a step, the width of the wall thickness of the respective Microfluidic line corresponds.

The increasing establishment of microtechnology also in chemical Analytics enables u. a. the development of measuring devices, in addition to short Analysis times and a high sample throughput a precise recording of Ensure measurement data. Miniaturized analyzers as well as the smallest Devices for sampling also result in portability of the Devices as well as low energy and chemical consumption.

Hand in hand with the development of such sampling and analysis systems there is also the search for suitable fasteners. Only under this A requirement can be a simple and effective requirement Sample transfer can be guaranteed. Especially for analytical It is very important in applications that the connectors for the Fluid lines do not result in dead volumes. Dead volumes can increase for example, form behind step-shaped widenings that only over Diffusion and are not accessible via convection. Therefore they remain Dead volumes contaminated, even if the connecting element is rinsed out.  

During the measurement, the contaminants slowly diffuse out of the Dead volume into the analysis liquid and falsify the result.

Specific tests have been carried out for special analytical applications to develop dead volume free connectors for fluid lines. In the EP 0 636 882 A1 describes a multi-part connector that is exchangeable and a capillary column for gas chromatography as well as a heater and a Includes thermocouple. This connector can by a plug mechanism to the stationary part of a gas chromatograph, d. H. the injector and the Detector. The capillary ends of the Gas chromatographs and the connector are each in a sleeve Component of the connector, the bore of which tapers increasingly. in the coupled state, the two flat ends of the sleeves adjoin each other. There is a sealing ring between the two sleeves for sealing.

EP 0 604 018 A1 describes a capillary connector for chromatography known, the inner bore is conical on both sides, wherein the opening angle is the bevel angle of the arranged around the capillaries Can correspond to ferrules. The capillaries protrude into one on both sides Connection channel into it, the diameter of which is the outer diameter of the Capillaries. The conical bore of the capillary connector is used to insert the capillaries into the connection channel as non-destructively as possible. The capillary connector is preferably made of glass to high To be able to withstand temperatures.

EP 0 706 047 A1 describes a two-part connector for capillary columns for chromatography. The capillary ends protrude into the connector halves, which are made of ceramic, preferably ZrO ₂ or SiO ₂ . The two connector halves are pressed against one another by mechanical devices. In order to ensure a tight connection between the two connector halves, the respective contact surfaces are convex.

The patent US 4 787 656 discloses a screwable coupling element for capillaries. The two capillaries to be coupled are elastic Ferrule fed to each other. The ferrule is tapered Recess within a screw cap. The screw caps grip via a thread into each other and the ferrule is in the narrowing Pressed recess so that the two capillaries through the ferrule to the outside sealed and fixed. The ferrule is made of compressible Material. Depending on the design of the ferrule, capillaries can also be used different radii.

In WO 96/36425 a connector for coupling a Described electrophoresis device with a mass spectrometer, the one has additional supply options for solvents. The Connector consists of a solid, outer sleeve and a internal elastic tube that is slightly longer than the sleeve. The two  Capillaries are inserted into the tube from both sides until they are with their adjoin flat ends. By ferrule screw caps, which on the ends of the tube protruding from the sleeve and threaded the pipe can grip the inner surface of the sleeve be upset. The capillaries are secured by compression sealed.

All these approaches have in common that dead volumes are not complete can be avoided. It is only with the greatest effort possible to grind the capillary ends so that they actually without Collide the gap. The connecting devices themselves are designed very complex and consist of many individual parts. Backing up and Sealing of the capillaries via radial pressure can occur if the Screw closures despite pressure distribution by a ferrule for damage of the capillary. Especially in analytical applications where one often has to work at temperatures higher than room temperature, it can occur that after application of too high radial pressure the capillary becomes can no longer be detached from the ferrule.

WO 98/33001 describes one possibility, the smallest Introduce quantities of liquid into chemical systems integrated on chips. For this purpose, a silicon wafer is perpendicular to the surface in two successive sections etched a cylindrical channel. In the first The diameter corresponds to the outside diameter of the section capillary. In the second section of the channel corresponds to Diameter that of the inner diameter of the capillaries, so that dead volumes be avoided. One can be placed on the wafer structured in this way Guide structure made of elastic plastic can be attached, the one has a tapered bore which is coaxial with the etched channel in the Wafer runs. The smallest bore diameter of the guide structure can be slightly smaller than the outer diameter of the capillaries, so that a  simply inserted capillary secured by the guide structure and is sealed. It also mentions the possibility of two wafers glue in mirror image to each other, so that a coupling device for two capillaries are created. This coupling device is very simple handle, since the two capillaries only have to be inserted, however the production of this coupling device is very complex. Moreover this coupling device can only be used for certain applications deploy.

The object of the invention is a connector for microfluidic lines that is easy to use, for as many applications as possible can be used and is suitable for mass production. Moreover the connector is intended to connect the microfluidic lines free of dead volume enable.

This object is achieved by a connector according to claim 1.

The connector according to the invention is easy to use. It just has to the microfluidic lines are pushed into the corresponding receiving chambers to connect them to each other via the connection channel. The Securing and sealing the microfluidic line is due to the elasticity of the Connector material guaranteed. Since the reception chamber at least is narrower in places than the microfluidic line to be accommodated Radial pressure on the wall of the receiving chamber Microfluidic line.

The connector material should be chosen so that the friction securing and sealing the inserted microfluidic lines supported, but not excessive insertion and removal impaired.  

Advantageously, the material is sufficiently elastic to the Connectors in the longitudinal direction stretch during the insertion process can. The tensile stresses that occur can be caused by the friction used to lower the microfluidic lines into the connector push in.

Just as simple as inserting the microfluidic lines into the connector they can be removed from it - without being damaged become. This ensures that both the connector and the microfluidic lines can be used several times. Both Microfluidic lines can be, for example, capillaries, Diffusion separators, fluid connections to analyzers or detectors, Micropipettes or any other fluid lines act because of their Inner diameter in the micrometer range of relatively small fluid volumes transport. The microfluidic lines can be made of glass, plastic or Be metal.

The connector according to the invention is used in analysis in Low pressure range up to about 5 bar pressure difference, for example in the Capillary electrophoresis, electrochromatography or low pressure Gas chromatography can be used universally.

Because of its one-piece design, there is no need for complex assembly and can Connectors according to the invention inexpensively as a mass article, for. B. impression-taking. Therefore, he can, for example, at medical diagnostic applications as an inexpensive disposable item be used.

The field of possible applications for the connector according to the invention we you. a. thereby expanded that the receiving chambers any Microfluidic line cross sections can be adapted. You can  Microfluidic lines of different cross sections and different dimensions.

One obtains a dead volume-free connection of the microfluidic lines in that the receiving chambers to the connecting channel over a step border, the width of the wall thickness preferably over the entire Corresponds to the extent of the respective microfluidic line. On the other hand, the Cross-section of the connecting channel in the receiving chamber itself subsequent area the inner cross section of the corresponding Microfluidic lines adapted. From a fluidic point of view it is also advantageous if the cross-section changes during the transition from the microfluidic line into the Connection channel not changed. Another advantage is that the stage when inserting the microfluidic line into the receiving chamber serves as a stop and sealing surface. Because the steps are made of elastic material exist and the end faces of the microfluidic lines are pressed into them are the requirements for the planarity of the end faces less than with conventional connectors, where the end faces of the Collide microfluidic lines directly.

Especially when connecting microfluidic lines with circular The connecting channel becomes a cross-section but different radii preferably conical or parabolic to determine the flow behavior to improve the fluid. In certain applications, the flow can can also be improved by other configurations of the connecting channel.

Depending on the application, the connector is a connector for two Fluid lines or designed as a T or Y piece or as a cross connector. In particular, the connectors are suitable for more than two microfluidic lines for applications such as derivatization in analytics, dividing volume flows in order to send them to different analysis systems, Detectors, microreactors, extraction units, mixers, etc.  to connect, or to connect reaction streams. The The connector according to the invention can also be used for the coupling Microdosing systems are used.

For analyzes or syntheses in large numbers parallel to each other run, the connector is preferably an array of two or more Connection channels with the adjacent receiving cavities formed, the connecting channels at least in a row or are arranged as a matrix.

In a preferred embodiment opens into the connecting channel additional cavity open to the outside to accommodate sensors. there it can be optical, electrochemical, physical or any other sensors act. With the help of these sensors, physical and / or chemical properties of the fluid flowing through, for example via electrochemical or spectroscopic methods or also Temperature measurements are monitored.

Especially if one of the microfluidic lines is a packed one Column, a frit is preferably arranged in the connecting channel, to prevent the packing material from entering the other microfluidic line penetrates.

To strengthen the sealing effect are on the inner wall Receiving chambers one or more beads that extend over the entire Extend circumference and / or knobs formed. The beads and / or pimples narrowing the receiving chamber in places, so that an additional Radial pressure is exerted on the microfluidic line.

In a preferred embodiment, the one according to the invention Connector made from an elastomer. Here are silicone rubber,  Rubber compounds or polyurethane resins. Is particularly preferred thereby silicone rubber. Because silicone rubber is non-conductive, connectors can made of silicone rubber also for electroanalytical applications such as B. the Capillary electrophoresis can be used. The is advantageous Connectors resistant to negative and positive pressure up to 5 bar.

The connector according to the invention is advantageously molded manufactured. A preferred method is reaction casting. For the Production by reaction casting can be a multi-part mold for the External shape of the connector and mandrels arranged in this form use. The mandrels form cavities for the receiving chambers and Connection channels and sensors if necessary. The mandrels are manufactured using Spark erosion with a precision of ± 1 µm.

Preferably, receiving chambers with a circular cross section have one Diameter or receiving chambers with any cross section Height or a width of 2 mm and particularly preferably of ≦ 500 µm on.

The invention will be explained in more detail with reference to the following figures. Show:

Fig. 1a, 1b, a connector for capillary electrophoresis,

Fig. 2 receiving chambers with different cross-sectional shapes and the associated connecting channel,

Fig. 3 a section through a T-connector,

Fig. 4 is an isometric view of a T-connector,

Fig. 5 is a cross section through a connector,

Fig. 6 is a formed as an array connector,

Fig. 7 shows a connector having cavities for accommodating sensors,

Fig. 8 is a connector for electrical chromatography with packed columns,

Fig. 9 shows a connector with beads.

In Fig. 1a, a connector 10 is shown for direct sample application for capillary electrophoresis. It serves to connect a microdeudder 60 to a capillary 50 (see also FIG. 1b). It is a connector 10 with two receiving chambers 31 , 32 , the radius of the receiving chamber 31 being larger than the radius of the receiving chamber 32 . The two receiving chambers 31 , 32 are connected via the conical connecting channel 21 . At the transitions between the receiving chambers 31 , 32 and the connecting channel 21 , steps 24 a, b are formed, the height of which corresponds to the wall thickness of the microfluidic lines to be inserted into the connector 10 .

In Fig. 1b, the connector 10 is shown for direct sample application of a Mikrodenuder 60 for capillary electrophoresis of Fig. 1 with inserted Mikrodenuder 60 and plugged fused silica capillary 50th The microdenuder 60 is a tube coated on its inner surface with adsorbent, which acts as a diffusion separator. The connector 10 connects the microdenuder 60 free of dead volume to a polyamide coated quartz glass capillary 50 for capillary electrophoresis. The microdenuder 60 and the quartz glass capillary 50 have different inside and outside diameters. In particular, the microdenuder 60 must remain interchangeable since it is used for sample collection.

The capillary 50 and the microde rudder 60 can be fastened in the plug connector 10 by plugging them into the plug connector 10 . The connector 10 has a receiving chamber 32 ( FIG. 1 a) with a smaller radius for receiving the capillary 50 , a conical connecting channel 21 and then a receiving chamber 31 ( FIG. 1 a) with a larger radius for receiving the microdeudder 60 . The radii of the receiving chambers 31 and 32 ( FIG. 1a) are somewhat smaller than the outer radii of the capillary 50 and the microdeudder 60 . The forces arising from the expansion of the connector material enable the capillaries to be fixed and sealed.

Silicon rubber was chosen as the material because it is chemically resistant and flexible and is non-conductive. These properties are for use in the Electrophoresis is important and leads to pressure resistance of up to approx. 1 bar Vacuum.

The outside diameter of the microdeudder 60 is 435 µm and its inside diameter is 320 µm. The outside diameter of the capillary 50 is 363 µm and its inside diameter is 75 µm. The connector 10 itself has the external dimensions of 3 mm × 3 mm × 12 mm. When choosing the wall thickness of the connector 10 , a minimum wall thickness must be maintained, which is determined differently depending on the material and application, so that there are no deformations at higher pressures. These deformations could lead to dead volumes.

Another advantage of silicone rubber is that this material is transparent. In this way it can be checked visually whether the capillary 50 or the microdenuder 60 has been pushed in as far as the stop in the form of the steps 24 a, b ( FIG . The stop is formed by the fact that the cross sections of the receiving chambers 32 and 31 correspond to the cross sections of the capillary 50 and the microdeudder 60 , but the cross section of the connecting channel 21 in the border area to the respective receiving chambers 31 , 32 corresponds to the inner cross section of the capillary 50 and corresponds to the microdeudder 60 . As a result, a step 24 a or 24 b ( FIG. 1 a) forms at the boundary between the connecting channel 21 and the receiving chamber 31 or 32 , up to which the end face 51 of the capillaries 50 or the end face 61 of the microdeudder 60 into the plug connector 10 must be inserted.

The length of the connecting channel 21 must be calculated specifically for each application. It must be at least so long that there are no dead volumes. The optimal shape of the connecting channel 21 must also be recalculated for each application. In the manufacture of the connector 10 , depending on the elasticity of the material, length tolerances of 3 to 4% are permitted. The connector 10 shown in Fig. 1 was made by reaction casting.

FIG. 2 shows the receiving chamber 34 with a square cross section and the receiving chamber 35 with a circular cross section, the outer contour of the connector 10 not being shown. For example, for applications in capillary electrophoresis, cylindrical capillaries are better suited for the electrophoresis step and capillaries with a square cross-section are better suited for optical detection. In order to ensure a dead volume-free connection together with optimal flow conditions, the connecting channel 20 is designed in such a way that its cross-section gradually changes from circular - at the border to the receiving chamber 35 with a round cross-section - into square - at the border to the receiving chamber 34 with a square cross-section . For this purpose, four flat isosceles triangles, the bases of which form the four sides of the square cross section of the connecting channel 24 , engage in four curved isosceles triangles, the bases of which form the circular shape of the cross section of the connecting channel 24 on the border to the receiving chamber 35 . The step 24 a is correspondingly ring-shaped and the step 24 b like a hollow square.

In Fig. 3 a section through a T-shaped connector is shown. The receiving chambers 30 a, 30 b and 30 c are arranged in a plane at 90 ° or 180 ° to each other. They are all connected to one another by a T-shaped connecting channel 22 , which borders the corresponding receiving chambers 30 a, b, c via the steps 24 a, b, c. Such connectors 10 are used, for example, in gas chromatography or also in gas chromatography coupled with mass spectrometry, since an additional carrier gas often has to be admixed to the analyte there.

In order to further clarify the arrangement of the T-shaped connector 10 , a perspective illustration of this connector 10 is shown in FIG .

In Fig. 5 is a section through a cross-shaped connector. The receiving chambers 30 a, 30 b, 30 c and 30 d are arranged in a plane perpendicular to one another and are connected by a cross-shaped connecting channel 23 which is connected to the corresponding receiving chambers 30 a, b, via the steps 24 a, b, c, d. c, d borders. Cross-shaped connectors can be used for derivatization in analytics. For example, two fluid reactants, which must be controlled separately, are supplied separately. Such methods are also known under the keyword gradient technology.

In automated, parallelized analysis or synthesis, it is useful to use connectors 11 designed as an array. Such an array is shown in FIG. 6. In one plane the coaxially arranged receiving chamber pairs 30 a and c, 30 'a and c, 30 ''a and c and 30 ''' a and c are arranged in a row. A third receiving chamber 30 b, 30 'b, 30 ''b and 30 ''' b is arranged perpendicular to the respective axes of these pairs.

The receiving chambers 30 a-c, 30 'ac, 30 ''ac and 30 ''' ac are connected by the T-shaped connecting channels 22 , 22 ', 22 '', 22 '''.

In order to be able to monitor processes or certain properties of the fluid, it is advantageous to be able to measure these properties in situ. For this purpose, in the embodiment of the connector 10 according to the invention shown in FIG. 7, two additional cavities 40 a and 40 b are provided perpendicular to the connecting channel 20 , which connects the two receiving chambers 30 a and 30 b, through which measuring sensors can be inserted into the fluid . Depending on which property is to be measured, it can be, for example, an electrode, a light guide or a temperature sensor, etc.

In order to also be able to use the connector 10 as a connector for packed columns, a special embodiment is provided, as shown in FIG. 8. The packed column is received by the receiving chamber 31 , the receiving chamber 32 receives the capillary. A frit 29 is arranged in the conical connecting channel 21 . It serves as a filter and prevents filling material from the packed column from entering the capillary, clogging or damaging it and falsifying the measurement result.

For applications where higher pressures occur, it is necessary to increase the radial forces that act on the fluid lines. For this purpose, in the connector 10 shown in FIG. 9, beads 39 are formed in the receiving chambers 30 a, b. These are circumferential beads. They increase the radial forces that act on the microfluidic lines without significantly increasing the frictional forces. Increased frictional forces would be obtained if the receiving chambers 30 a, b were made narrower overall in order to increase the radial force. Increased frictional forces would be detrimental to simple insertion and removal of the microfluidic lines.

Reference list

10th

Connectors

11

Connectors as an array

20th

Connecting channel

21

conical connection channel

22

T-shaped connection channel

23

cross-shaped connecting channel

24th

a, b, c, d level

29

Frit

30th

ad admission chamber

30th

'ac reception chamber

30th

"ac reception chamber

30th

'''ac receiving chamber

31

Receiving chamber with a larger radius

32

Receiving chamber with a smaller radius

34

Admission chamber with a square cross section

35

Receiving chamber with a circular cross-section

39

bead

40

a, b sensor cavity

50

capillary

51

Face

60

Microdenuder

61

Face

Claims (11)

1.Connector for at least two microfluidic lines to be connected to one another with at least 2 receiving chambers and with at least one connecting channel connecting the receiving chambers, the receiving chambers adjoining the connecting channel via a step whose width corresponds to the wall thickness of the respective microfluidic line, characterized in that the connector is made in one piece is made of a flexible, pressure-resistant material and that the dimensions of the individual receiving chambers are chosen such that the microfluidic line inserted into the respective receiving chamber is kept under radial pressure. 2. Connector according to claim 1, characterized in that the connecting channel ( 20 ) is conical or parabolic. 3. Connector according to claim 1 or 2, characterized in that the connector ( 10 ) with two receiving chambers ( 30 a, b) is sleeve-shaped. 4. Connector according to one of claims 1 to 3, characterized in that the connector ( 10 ) is designed as an array ( 11 ) by in a connector two or more connecting channels ( 20 ) with the adjoining receiving chambers ( 30 ) in at least one row are arranged. 5. Connector according to one of claims 1 to 4, characterized in that at least one outwardly open cavity ( 40 ) for receiving sensors with the at least one connecting channel ( 20 ) is in flow connection. 6. Connector according to one of claims 1 to 5, characterized in that a frit ( 29 ) is arranged in the connecting channel ( 20 ). 7. Connector according to one of claims 1 to 6, characterized in that one or more beads and / or knobs ( 39 ) projecting into it are formed in the receiving chamber ( 30 ). 8. Connector according to one of claims 1 to 7, characterized characterized in that it is made of an elastomer, in particular Silicone rubber, rubber compound, polyurethane resin. 9. Connector according to one of claims 1 to 8, characterized characterized that it is pressure-resistant up to 5 bar negative and positive pressure is designed. 10. Connector according to one of claims 1 to 9, characterized characterized in that it is impression technology, in particular by Reaction casting is made. 11. Connector according to one of claims 1 to 10, characterized in that the dimension of at least one receiving chamber ( 30 ) in at least one direction perpendicular to the corresponding step ( 24 ) is less than or equal to 2 mm and particularly preferably less than or equal to 500 µm.