Microfluidic Device

Abstract

A microfluidic device includes a chamber, on two sides of which lying opposite each other in a first direction, a respective first distributor is provided in order to produce a laminar flow in the first direction. Each of the first distributors has at least one branching point, at which a channel is divided into at least two channels. The at least one branching point of the first distributor is arranged in such a way that a first connection channel is connected to a plurality of first connection points of the chamber by means of the first distributor.

Claims

1. A microfluidic device comprising: a chamber comprising a first side and a second side, which are opposite one another in a first direction; and a respective first distributor located on each of the first and second sides, the respective first distributors configured to generate a laminar flow in the first direction, wherein each of the respective first distributors includes at least one first branching site at which a channel divides into at least two channels, and wherein the at least one first branching site of each respective first distributor is arranged such that a first connection channel is connected to a plurality of first connection points of the chamber via the respective first distributor.

2. The microfluidic device as claimed in claim 1, wherein: the chamber further comprises a third side and a fourth side, which are opposite one another in a second direction that is different from the first direction; the microfluidic device further comprises a respective second distributor arranged on each of the third and fourth sides and configured to generate a laminar flow in the second direction; each of the second distributors has respectively at least one second branching site at which a channel divides into at least two channels; and the at least one second branching site of each respective second distributor is arranged such that a second connection channel is connected to a plurality of second connection points of the chamber via the respective second distributor.

3. The microfluidic device as claimed in claim 2, wherein the first direction is perpendicular to the second direction.

4. The microfluidic device as claimed in claim 2, further comprising: at least one pump connected to one of the respective first distributors via a first valve and to one of the respective second distributors via a second valve.

5. The microfluidic device as claimed in claim 2, further comprising: at least one respective shutoff valve at at least one of the respective first or second distributors.

6. The microfluidic device as claimed in claim 1, wherein the chamber defines a plurality of indentations arranged as an array.

7. The microfluidic device as claimed in claim 1, further comprising: a silicon section in which at least the chamber and the respective first distributors are arranged.

8. An arrangement comprising: a microfluidic device comprising: a chamber comprising a first side and a second side, which are opposite one another in a first direction; and a respective first distributor located on each of the first and second sides, the respective first distributors configured to generate a laminar flow in the first direction, wherein each of the respective first distributors includes at least one first branching site at which a channel divides into at least two channels, and wherein the at least one first branching site of each respective first distributor is arranged such that a first connection channel is connected to a plurality of first connection points of the chamber via the respective first distributor; and an optical capture unit configured to capture a position of a sample within the chamber of the microfluidic device.

9. A method for operating a microfluidic device having a chamber, comprising: providing a sample in the chamber, generating a laminar flow through the chamber in a first direction, so that the sample arrives at a specifiable position in the first direction.

10. The method as claimed in claim 9, further comprising: method step: generating a laminar flow through the chamber in a second direction different from the first direction, so that the sample arrives at a specifiable position in the second direction.

11. The method as claimed in claim 9, further comprising: capturing a current position of the sample within the chamber with an optical capture unit; and setting the laminar flow based on the current position of the sample that was captured by the optical capture unit such that the sample arrives in the specifiable position.

Description

[0056] The microfluidic device and the method are more particularly elucidated below on the basis of figures. It should be pointed out that the figures and, in particular, proportions depicted in the figures are only schematic. The following are shown:

[0057] FIG. 1: a described microfluidic device,

[0058] FIG. 2: a further described microfluidic device,

[0059] FIG. 3: a flow diagram of a described method,

[0060] FIG. 4a, 4b: a microfluidic device during various method phases,

[0061] FIG. 5a, 5b: a further flow diagram of the described method,

[0062] FIG. 6: one design variant of a described device,

[0063] FIG. 7: an arrangement with a described device,

[0064] FIG. 8a to c: transport of a sample with a described device,

[0065] FIG. 9a to e: the operation of a pump in the described method, and

[0066] FIG. 10: an arrangement with a described device.

[0067] FIG. 1 shows a described microfluidic device 1. What is described here is the basic design of such a microfluidic device 1, in order to show how a particle can be moved in one plane in a controlled manner using the described microfluidic device 1. FIG. 1 is a sketch of one design variant of the described microfluidic device that allows precise positioning of a sample in one direction only.

[0068] The microfluidic device 1 has a chamber 2 which has a first direction 5 and two sides which are opposite to one another along the first direction 5 (a first side 7 and a second side 8). Respectively present on the first side 7 and on the second side 8 are first connection points 14, which are evenly distributed over the first side 7 and the second side 8. The first connection points 14 are supplied with fluid via first connection channels 12. Proceeding from the first connection channels 12, the liquid path branches by means of so-called first distributors 3 at branching sites 11 toward the first connection points 14. Preferably, there is a doubling of the number of subchannels at each branching site 11. In this way, multistage first distributors 3 are formed by the branching sites 11. With the aid of the distributors 3 and the first connection points 14, an exactly parallel flow is generated in the chamber 2. By means of said flow, a particle or a sample which is situated in the chamber 2 can be moved very precisely in a first direction 5. In this principle, the laminar flow is especially generated by the first connection points each being divided into subclosures. If the channel dimensions at each branching site 11 remain as equal in size as in the input channel of the particular branching site 11, the flow rate is halved per split and so is the speed of the flow. The split-up channels at each branching site 11 are conducted into the volume of the plane in the chamber 2. The resultant laminar flow is preferably absolutely homogeneous or absolutely parallel in the chamber 2. The first distributors 3 constructed as described are very advantageous therefor. If said first distributors 3 are compared with a simplified variant of a channel enlargement from the first connection channel 12 toward the chamber 2, the first distributors 3 have the advantage that the expansion of the flow is done in an absolutely controlled manner in all planes and no turbulences at all can arise. The flow does not flow freely again until in the chamber 2. However, in the chamber, the flow is already slowed down by the expansion in the first distributors 3 to the extent that it is likewise no longer possible for turbulences to occur. A simple expansion of the flow toward the chamber would accordingly much more likely cause an inhomogeneous speed profile than the described first distributors 3 in the chamber 2. Also important for the microfluidic device 1 is that the first connection channels 12, the branching sites 11 and the first connection points 14 are, in each case, symmetrical on the first side 7 and the second side 8, i.e., exactly opposite to each first connection point 14 on the first side 7 is precisely one first connection point 14 on the second side 8. The liquid flow from the first connection point 12 on the first side 7 toward the first connection point 12 on the second side 8 is first fanned out by the first distributor 3 on the first side 7 and then brought back together by the first distributor 3 on the second side 8. The liquid can flow in the first direction 5 either toward the first side 7 or toward the second side 8. This is possible by a reversal of a conveying direction of a pump connected to the first connection channel 12.

[0069] FIG. 2 shows one variant of the microfluidic device 1, which is expanded to a two-dimensional operation compared to the variant of the microfluidic device 1 in FIG. 1. The principle elucidated for one dimension on the basis of FIG. 1 is expanded to two dimensions in FIG. 2.

[0070] Besides first connection channels 12 and first connection points 14 on the first side 7 and the second side 8, what are also present as per the design variant in FIG. 2 are second connection channels 13 and second connection points 15 having respectively corresponding second distributors 4 on the third side 9 and the fourth side 10. Particularly preferably (as depicted here too), the chamber 2 is rectangular. Particularly preferably, the chamber 2 is even square. The first connection points 14, the first connection channels 12 and the first distributors 3 are preferably designed just like the second connection points 15, the second connection channels 13 and the second distributors 4. All the above explanations of first connection points 14, first connection channels 12 and first distributors 3 accordingly also apply to second connection channels 13, second connection points 15 and second distributors 4. What is depicted in detail in the chamber 2 in FIG. 2 is how particles in a fluid plane in the chamber 2 can be moved in a controlled manner in a first direction 5 (may also be called X-direction) and in a second direction 6 (may also be called Y-direction). Particularly preferably, a peristaltic pump which can be operated in a forward and backward manner is used for operation of such a microfluidic device 1. It is then possible for particles to be moved to and fro as desired within the plane in the chamber 2. The flow can be used only in one direction at a time. Respectively provided at the connection channels 12 and the second connection channels 13 are shutoff valves 19, by means of which a liquid flow in the chamber 2 can be stopped at a stroke.

[0071] A particle or a sample can be introduced into the chamber 2 through any one of the connection channels 12, 13. Once it has arrived in the chamber 2, a particle or a sample within the chamber 2 can then be deterministically (exactly) positioned.

[0072] FIG. 3 shows a flow diagram of the described method. Here, the chamber 2 is depicted schematically in the microfluidic device 1. Step A comprises the placement of a sample 23 in the chamber 2. This is followed by executing method steps B1 and B2, by means of which the sample 23 can be positioned in a first direction 5 and in a second direction 6, this being depicted here by arrows within the chamber 2.

[0073] FIG. 4a and FIG. 4b show, on the basis of sketches of the microfluidic device 1, how particles or samples are moved. For movement in a first direction 5, valves are closed at second connection channels 13 and at second distributors 4. A liquid flow is in contact with first connection channels 12 and first distributors 3. The sample 23 is accordingly moved in the first direction 5. There is no movement in the second direction 6. This is depicted in FIG. 4a. To move the sample in the second direction 6, first connection channels 12 and first distributors 3, or valves arranged there, are closed. A liquid flow takes place via second distributors 4 and via second connection channels 13. The sample then no longer moves in the first direction 5. There is movement in the second direction 6. FIG. 4b sketches how the sample 23 moves accordingly.

[0074] FIG. 5a and FIG. 5b illustrate how various pumping sequences (corresponding to steps B1 and B2) are carried out in the context of the described method. FIG. 5a depicts a sketch of the movement of the sample 23 in the chamber 2 in the first direction 5 and in the second direction 6. FIG. 5b depicts a sequence of individual pump operations as per method steps B1 and B2 (first pumping action 24, second pumping action 25, third pumping action 26 and fourth pumping action 27) over time t (depicted here on a timeline) that corresponds to the movement 23 depicted in FIG. 5a.

[0075] FIG. 6 depicts an arrangement 21 comprising a microfluidic device 1. The arrangement 21 depicted in FIG. 6 comprises only one peristaltic pump 16. First distributors 3 or second distributors 4 are respectively arrangeable via first valves 17 and second valves 18 on the chamber 2, so that it is possible, only with one pump via control of the first valves 17 and the second valves 18, to select which forks of a flow path proceeding from the pump 16 can respectively open or close. The sample 23 can accordingly be moved in the first direction 5 or the second direction 6 in the chamber 2.

[0076] FIG. 7 shows a microfluidic device 1 in an arrangement 21, with means for further process steps being depicted here as well. The microfluidic device 1 has the chamber 2. The chamber 2 can be monitored by an optical capture unit 22 in order to identify where a (sample not depicted here) is currently situated within the chamber 2. The optical capture unit 22 is part of an optical sensor system. Particles or samples in the chamber 2 can, for example, be identified via fluorescence marker, phase contrast or bright-field recordings, which are carried out using the optical capture unit 22. By means of image evaluation using the optical capture unit 22, for example in a position capturer 29 which is intended therefor and which can comprise a controller, it can then be established whether a particular particle or a particular sample is situated in the chamber and where it is exactly situated. The desired position of a particle or a sample in the chamber 2 is defined. The corresponding X- and Y-components in the first direction and the second direction can then be calculated, and pumping can be carried out accordingly in the respective direction using the (pump not depicted here). The nondepicted pump is part of a flow generator 30 which generates the flows in the chamber 2. For operation of the microfluidic device 1 or the arrangement 21, a control panel 28 is preferably present.

[0077] The control panel 28, which comprises a joystick or arrow keys for example, can actively actuate the flow generator 30.

[0078] FIG. 8 demonstrates how a sample or a particle is transported into an indentation 20 (may also be called cavity, pot or cell) and then fills the indentation 20. FIG. 8a depicts the microfluidic device 1 comprising the first distributors 3 and the second distributors 4 and the chamber 2, with the indentations 20 being situated in the chamber and arranged in the manner of an array in each case. Also depicted is a sample 23 on its way into one of the indentations 20, the sample being steered on said way with the laminar flows by the first distributors and the second distributor 4. The sample 23 arrives into the respective indentation 20 preferably by gravity. Preferably, the transport speed of the sample 23 in the chamber 2 in the first direction 5 and in the second direction 6 is, however, so great that the sample 23 needs a certain time until it sinks into the intended indentation 20. The sample 23 can thus be successfully transported over indentations 20.

[0079] FIG. 8b shows a section of the chamber 2 with the indentation 20, with the sample 23 here being situated above the indentation 20.

[0080] FIG. 8c shows how the sample 23 sinks into the indentation 20 from the chamber 2 with the aid of gravity.

[0081] FIG. 9a to FIG. 9e shows a method with use of a pump system with a microfluidic device in a two-phase system. Here, the indentations 20 are initially filled with an aqueous phase or water 33 (see FIG. 9b). FIG. 9c depicts the transport of the sample 23 in oil 32, which prevents contamination of the sample 23, in the chamber 2. FIG. 9d depicts how the sample 23 sinks into water 33 in the indentation 20 from the oil 32. FIG. 9e depicts how the sample 23 is transported over the chamber 2 or over the water 33 present in the chamber 2 by the flowing oil 32.

[0082] This is shown again by FIG. 9a in the top view of the microfluidic device 1 with the chamber 2, the first direction 5, the second direction 6, the first distributors 3 and the second distributors 4.

[0083] FIG. 10 shows one variant of the microfluidic device 1, the aim of which is to explain the production of the microfluidic device 1. What can also be seen here are the first distributors 3, the second distributors 4, the points 16 with the first valves 17 and the second valves 18 and also the chamber 2.

[0084] What can be seen is that the chamber with the array of indentations that is situated therein and not depicted here can be situated of a silicon chip, which can be manufactured into a lap and chip cartridge and for example be produced an injection mold. Since very small channel sizes and structures are efficiently producible on a silicon chip, the first distributors 3 and the second distributors 4 are also arranged on the silicon chip. The silicon chip thus forms the chamber 2 and also the first distributors 3 and the second distributors 4. The silicon chip is integrated in a splash-protection housing, on which liquid paths from the pump 16 or from the first valves 17 and the second valves 18 proceed to the first connection channel 12 and the second connection channel 13.