DEVICE FOR SEPARATING BUBBLES FROM A FLUID

Abstract

The present invention relates to a device and a method for separating bubbles from a fluid comprising a chamber through which a fluid can pass. According to the invention the device is characterized in that the inner chamber wall has a geometry that generates within said chamber a continuous flow and at least one area with a discontinuous flow which has a low flow velocity so that bubbles remain at the inner chamber wall in said area and thus are separated from the fluid flowing out from the chamber.

Claims

1. Method for separating bubbles from a fluidic sample, comprising the following steps: a) transferring the fluidic sample through a bubble trap which is connected to an analyzing device, b) forming a continuous flow and at least one area with a discontinuous flow of the sample in the bubble trap, c) retaining bubbles from the sample flowing out the bubble trap by absorbing the bubbles at the inner wall of the bubble trap in the area of the discontinuous flow.

2. The method according to claim 1, characterized in that the flow within the chamber generates areas of distinct flow velocities encompassing at least one area with a high flow velocity and at least one area with a low flow velocity. (Seite 5, 7. Absatz)

3. The method according to one of the above claims, characterized in that the continuous flow comprises the area with a high flow velocity and the discontinuous flow comprises the area with a low flow velocity. (Seite 5, 7. Absatz)

4. The method according to one of the above claims, characterized in that the reduction of the flow velocity in the discontinuous flow has to reach a level, where the absorptive forces of the bubbles to the inner wall are higher than the forces which drag the bubbles into the effusing flow. (Seite 3, 5. Absatz)

5. The method according to one of the above claims, characterized in that the ratio of the flow velocity of the continuous flow and the flow velocity of the discontinuous flow is at least 2:1, preferred at least 5:1, more preferred at least 10:1, more preferred at least 15:1, more preferred at least 25:1, even more preferred at least 35:1 and most preferred at least 50:1. (Seite 5, 8. Absatz)

6. The method according to one of the above claims, characterized in that the area of high flow velocity and the at least one area with a low flow velocity are adjacent to each other.

7. The method according to one of the above claims, characterized in that the high flow velocity is at least 5 mm/s, preferably at least 10 mm/s and most preferably at least 20 mm/s.

8. The method according to one of the above claims, characterized that the low flow velocity is not more than 5 mm/s, preferably not more than 1 mm/s and most preferably not more than 0.5 mm/s.

9. The method according to one of the above claims, characterized in that the discontinuous flow comprises a chaotic flow or turbulences.

10. The method according to one of the above claims, characterized in that the discontinuous flow comprises at least one region of dead water.

11. The method according to one of the above claims, characterized in that a difference in velocity Δv is obtained in a distance Δx which leads to a ratio of the difference of velocity and the difference of distance Δv/Δx is in the region between 10 mms.sup.−1/mm and 20 mms.sup.−1/mm.

12. A device for separating bubbles from a fluid comprising a chamber (1), an afferent conduit (2) and an efferent conduit (3) guiding a fluid through said chamber (1), characterized in that the inner chamber wall has a geometry that generates within said chamber (1) a continuous flow and at least one area with a discontinuous flow, so that in the area of the discontinuous flow bubbles remain at the inner chamber wall and thus are separated from the fluid effusing from the chamber (1).

13. The device according to claim 12, characterized in that the chamber comprises in a plan view at least one circular shape, wherein the at least one circular shape has a radius from 0.5 to 2 mm.

14. The device according to claim 12, characterized in that the inner wall of the chamber, starting from the afferent conduit, has at least one convex bulge.

15. The device according to claim 12, characterized in that the chamber comprises in a three-dimensional view at least one section which is based on non-linear bodies.

16. The device according to claim 12, characterized in that the ratio of the chamber diameter to channel diameter in a cross sectional view perpendicular to the continuous flow is at least 4:1, more preferably at least 5:1, more preferably at least 6:1 and most preferably at least 7:1.

17. The device according to claim 12, characterized in that the chamber is part of a lab-on-a-chip system.

18. The device according to claim 12, characterized in that the device is a disposable.

19. Use of a chamber for separating bubbles from a fluid, characterized in that the inner chamber wall has a geometry that generates within said chamber a continuous flow and at least one area with a discontinuous flow, so that in the area of the discontinuous flow bubbles remain at the inner chamber wall and thus are separated from the fluid effusing from the chamber.

20. A fluidic, in particular microfluidic, system comprising a chamber, an afferent conduit and an efferent conduit guiding a fluid through said chamber, characterized in that the inner chamber wall has a geometry that generates within said chamber a continuous flow and at least one area with a discontinuous flow, so that in the area of the discontinuous flow bubbles remain at the inner chamber wall and thus are separated from the fluid effusing from the chamber.

Description

FIGURES

[0053] The invention will be explained in further detail with reference to specific embodiments as shown in the drawings, in which

[0054] FIG. 1 shows a device according to the invention in a first embodiment, wherein FIG. 1a is a plan view and FIG. 1b is a perspective view;

[0055] FIG. 2 shows a plan view of a device according to the invention in a second embodiment;

[0056] FIG. 3 shows a plan view of different geometries of a device according to FIG. 2; and

[0057] FIG. 4 shows the devices of FIG. 1 and FIG. 2 arranged on a lap-on-a-chip system.

EXAMPLES

[0058] FIG. 1 shows a first embodiment of a device for separating bubbles from a fluid according to the invention. To carry out the experimental study polycarbonate chips with various chamber geometries were fabricated by milling. The chips consist of two half shells, which are both structured as due to the height of the cartridge as half shells from 2 mm, furthermore the chamber is divided between the two half-shells.

[0059] FIG. 1a shows a plan view of a chamber 1 and an afferent conduit 2 and an efferent conduit 3, whereas FIG. 1b shows a perspective view of the chamber 1 and the afferent conduit 2 and the efferent conduit 3. The width of the afferent and the efferent conduit 2, 3 in FIGS. 1 to 4 is 0.5 mm.

[0060] A ramp at the inlet and outlet of the chamber can be added, so that no liquid remains standing in this chamber. Behind each chamber is a pentagonal viewing chamber which has a volume of 10 μl. The viewing chamber is laid out flat with a height of 1 mm, so that the bubbles, forwarded from the chamber, lie approximately in a plane, and can be well observed.

[0061] For the variation of the device mainly the radii of the circular shapes are changed. This is accompanied by a change in size of the entire chamber which has the overall shape of cloud with respect to a plan view. Furthermore, two different forms of the side walls are being tested at input and output (respectively afferent and efferent conduit) of the structure. Table 1 gives an overview of possible geometries. Here, R is the radius of the circular shapes, d.sub.1 and d.sub.2 are the distance between the center of one circular shape to the center of the conduit, d.sub.3 and d.sub.4 are the distance between the center of one circular shape to another circular shape, both lying on the same axis, alpha.sub.1 (α.sub.1) and alpha.sub.2 (α.sub.2), and l.sub.1 and l.sub.2 are the dimensions of the splines, which lead to two different forms of the side walls.

TABLE-US-00001 TABLE 1 Examples for possible geometries of the first embodiment Example R [mm] d.sub.1 [mm] d.sub.2 [mm] d.sub.3 [mm] d.sub.4 [mm] alpha.sub.1 [°] alpha.sub.2 [°] l.sub.1 [mm] l.sub.2 [mm] 1 0.7 0.6 0.7 1.0 1.0 60 50 1.0 1.5 2 0.9 0.4 0.5 1.0 1.0 60 50 1.0 1.5 3 0.8 0.9 1.0 1.5 1.5 60 50 1.0 1.5 4 1.0 0.7 0.8 1.5 1.5 60 50 1.0 1.5 5 1.2 0.5 0.6 1.5 1.5 60 50 1.0 1.5 6 1.4 0.3 0.4 1.5 1.5 60 50 1.0 1.5 7 0.7 0.6 0.7 1.0 1.0 90 50 1.0 1.5 8 0.9 0.4 0.5 1.0 1.0 90 50 1.0 1.5 9 0.8 0.9 1.0 1.5 1.5 90 50 1.0 1.5 10 1.0 0.7 0.8 1.5 1.5 90 50 1.0 1.5 11 1.2 0.5 0.6 1.5 1.5 90 50 1.0 1.5 12 1.4 0.3 0.4 1.5 1.5 90 50 1.0 1.5

[0062] Chip half shells were joined by Silpuran 4200, wherein Silpuran is a registered trademark and refers to silicone rubber compounds. The devices of the first embodiment are open upward so that the lyophilizates can be introduced here. In the experiments, each device was loaded with two lyophilizates. One of the beads contains the primer and the other all the remaining reagents. The lyophilized compositions comprise the following components:

TABLE-US-00002 No. Component 1 Buffer 2 Salt 3 Albumine 4 dNTPs 5 Primer 6 Probes 7 Polymerase 8 Matrix forming agent

[0063] The conduit structure is at the bottom of the structured polycarbonate plate and is sealed with double-sided PCR sheet and an unstructured plate. The chip is here contacted with a silicone conduit having an inner diameter of 2.1 mm and an outer diameter of 4 mm. For the experimental procedure, the peristaltic pump “Peristaltic Pump P-1” from Pharmacia Fine Chemicals was used. With the Peristaltic Pump P-1 flow velocities of about 1 ml/h to approximately 500 ml/h depending on the choice of the conduit inside diameter can be obtained, the pumping speed is infinitely adjustable. The conduit structure was observed with a microscope at a magnification of 2 to 4. For the dissolution of the various lyophilizates the following experimental parameters were chosen:

[0064] Solvent: HPLC-water

[0065] Volume of solvent: 20 μl

[0066] Pumpingrate: 2.6 μl/s

[0067] HPLC water was used as solvent because this is usually used when preparing reagents in biochemistry.

[0068] It can be noted that with increasing chamber size the flow through of the device of the first embodiment according to the invention increased in height on the one hand and on the other hand an increased potential for chaotic flow was observed.

[0069] FIG. 2 and FIG. 3 show a second embodiment of a device for separating bubbles from a fluid according to the invention. In a plan view the device of the second embodiment according to the invention is a circular shape with a diameter of 2.5 mm and a conduit with a cross sectional diameter of 0.7 mm which intersects the circular shape tangential. Thereafter, the conduit is shifted by 0.25 mm upwards and the circular shape is connected with the lower contour of the conduit tangentially, so that a nozzle is formed. This procedure is provided in geometry 1 of FIG. 3. For the second geometry, the conduit is again shifted upwards by 0.25 mm. Because the tip of the nozzle is fixed to the conduit, the angle of opening of the nozzle will also change. This scheme is continued until geometry 8 of FIG. 3. The basic idea of this strategy is that it is predominantly the nozzle which causes the gas bubbles-retaining effect in the second embodiment of a device according to the invention. The further experiments were carried out in the same manner as described above

[0070] As a result, it can be stated that the first chamber geometry shows a pronounced region with a low flow velocity above the curve. Due to the migration of the conduit toward the chamber center, these low flow velocities get smaller and do no longer occur at the fifth geometry. The chamber is flowed through increasingly more evenly. In the first chamber geometry a vortex in the rounding of the second embodiment of a device according to the invention is formed and the chamber is completely flowed through in height. In the third and fourth geometry these vortexes no longer occur and the chamber is no longer flowed through in the upper quarter. Additionally it can be observed starting from the fifth chamber geometry that the chamber is increasingly less flowed through in its width. In the evaluation of the experiment, it was found that all the chamber geometries retained the gas bubbles similar effectively.

[0071] FIG. 4 shows the first and the second embodiment of a device according to the invention arranged in a lap-on-a-chip system. The chambers according to the first and second embodiment of a device according to the invention are located directly before the PCR chamber. The gas bubbles retaining effect of the first and second embodiment is used for an optimal carrying out of the PCR. Since the chambers of the invention separate the gas bubbles from the effusing fluid, no bubbles enter the PCR chamber. Thus, an optimal functioning of the PCR is guaranteed.