MICROFLUIDIC DEVICE

Abstract

A microfluidic device (200) for separating a liquid L into first and second liquid components L.sub.1, L.sub.2 thereof is described. The microfluidic device (200) comprises an inlet (230) for receiving the liquid therethrough. The microfluidic device (200) comprises a first outlet (210) for the first liquid component L.sub.1, wherein the first outlet (210) is fluidically coupled to the inlet (230) via a first passageway (240). The microfluidic device (200) comprises a second outlet (220) for the second liquid component L.sub.2, wherein the second outlet (220) is fluidically coupled to the first passageway (240A) via a first set of N conduits 250 (250A, 250B, 250C, 250D, 250E), wherein N is a positive integer greater than 1, wherein respective conduits 250A, 250B, 250C, 250D, 250E of the first set of N conduits 250 divide from the first passageway 240A at respective divisions 252 (252A, 252B, 252C, 252D, 252E) from the inlet 230 therealong 240. The respective conduits 250A, 250B, 250C, 250D, 250E of the first set of N conduits 250 are arranged to, at least in part, equalize flowrate ratios at the respective divisions 252 (252A, 252B, 252C, 252D, 252E).

Claims

1-20. (canceled)

21. A microfluidic device for separating a liquid into first and second liquid components thereof, the microfluidic device comprising: an inlet for receiving the liquid therethrough; a first outlet for the first liquid component, wherein the first outlet is fluidically coupled to the inlet via a first passageway; and a second outlet for the second liquid component, wherein the second outlet is fluidically coupled to the first passageway via a first set of N conduits, wherein N is a positive integer greater than 1, wherein respective conduits of the first set of N conduits divide from the first passageway at respective divisions from the inlet there-along, wherein: the respective conduits of the first set of N conduits are arranged to, at least in part, equalize flowrate ratios at the respective divisions; the first passageway comprises a set of expansion members; and respective expansion members of the set of expansion members correspond with the respective conduits of the first set of N conduits.

22. The microfluidic device according to claim 21, wherein the respective conduits of the first set of N conduits are arranged to, at least in part, equalize flowrate ratios at the respective divisions by having respective fluidic resistances arranged to attenuate respective flowrates of the second liquid component therethrough.

23. The microfluidic device according to claim 22, wherein the respective fluidic resistances are provided, at least in part, by the respective conduits having respective lengths, cross-sectional areas, cross-sectional shapes and/or internal surfaces arranged to attenuate respective flowrates of the second liquid component therethrough according to, at least in part, respective liquid pressures at the respective divisions.

24. The microfluidic device according to claim 23, wherein the respective fluidic resistances are provided, at least in part, by the respective conduits having respective lengths arranged to attenuate respective flowrates of the second liquid component therethrough according to, at least in part, respective liquid pressures at the respective divisions.

25. The microfluidic device according to claim 21, wherein the first passageway tapers from the inlet towards the first outlet along at least a part of a length thereof.

26. The microfluidic device according to claim 21, wherein either: the first passageway curves from the inlet towards the first outlet along a first part of a length thereof, or the first passageway tapers along the first part of the length.

27. The microfluidic device according to claim 21, wherein either: the first passageway curves from the inlet towards the first outlet along a second part of a length thereof, or the first passageway has a constant cross-sectional area along the second part of the length.

28. The microfluidic device according to claim 21, wherein the first passageway defines a linear or a non-linear flow path of the liquid via the respective divisions.

29. The microfluidic device according to claim 21, wherein: the respective conduits divide from the first passageway at the respective divisions by being arranged at respective acute angles thereto, and respective intersections of the respective conduits and the first passageway at the respective divisions define arcuate flow paths of the second liquid component.

30. The microfluidic device according claim 21, wherein the first passageway comprises a set of constriction members, wherein respective constriction members of the set of constriction members correspond with the respective conduits of the first set of N conduits.

31. The microfluidic device according to claim 21, wherein a conduit of the first set of N conduits is arranged boustrophedonically, having parallel legs of equal lengths.

32. The microfluidic device according to claim 21, wherein the microfluidic device is arranged to reduce or avoid dead volumes.

33. The microfluidic device according to claim 21, wherein: the first outlet is fluidically coupled to the inlet via a second passageway; the second outlet is fluidically coupled to the second passageway via a second set of M conduits, M being a positive integer greater than 1, respective conduits of the second set of M conduits divide from the second passageway at respective divisions from the inlet there-along; and the respective conduits of the second set of M conduits are arranged to, at least in part, equalize flowrate ratios at the respective divisions.

34. The microfluidic device according to claim 21, wherein: the microfluidic device is a blood separation device, and the second liquid component comprises separated plasma.

35. A lab-on-a-chip device comprising a microfluidic device according to claim 21.

36. A method of separating blood using a microfluidic device according to claim 21, the method comprising: pumping or injecting the blood into the microfluidic device via the inlet; separating the blood into the first liquid component and the second liquid component, wherein the second liquid component comprises and/or is separated blood plasma; and collecting the second liquid component from the second outlet.

37. The method according to claim 36, wherein the second liquid component comprises one of: at most 10% leukocytes, platelets and/or erythrocytes by mass, at most 5% eukocytes, platelets and/or erythrocytes by mass, at most 3% eukocytes, platelets and/or erythrocytes by mass, at most 2% eukocytes, platelets and/or erythrocytes by mass, at most 1% eukocytes, platelets and/or erythrocytes by mass, at most 0.5% eukocytes, platelets and/or erythrocytes by mass, or at most 0.1% leukocytes, platelets and/or erythrocytes by mass.

38. The method according to claim 36, wherein the blood is diluted whole blood diluted by a ratio of one of: at most 10:1, at most 5:1, at most 2:1, or at most 1:1.

39. The method according to claim 36, wherein the blood is whole blood.

40. The method according to claim 36, comprising pumping or injecting the blood at a flow rate in one of: a range from 1 to 100 ml/hr, a range from 2 to 50 ml/hr, or a range from 5 to 30 ml/hr.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0139] For a better understanding of the invention, and to show how exemplary embodiments of the same may be brought into effect, reference will be made, by way of example only, to the accompanying diagrammatic Figures, in which:

[0140] FIG. 1 schematically depicts a microfluidic device according to an exemplary embodiment;

[0141] FIG. 2 schematically depicts a microfluidic device according to an exemplary embodiment;

[0142] FIG. 3 schematically depicts the microfluidic device of FIG. 2, in more detail;

[0143] FIG. 4 schematically depicts the microfluidic device of FIG. 2, in more detail;

[0144] FIG. 5 schematically depicts a microfluidic device according to an exemplary embodiment;

[0145] FIG. 6 schematically depicts the microfluidic device of FIG. 5, in more detail;

[0146] FIG. 7 schematically depicts the microfluidic device of FIG. 5, in more detail;

[0147] FIG. 8 schematically depicts a microfluidic device according to an exemplary embodiment;

[0148] FIG. 9 schematically depicts the microfluidic device of FIG. 8, in more detail;

[0149] FIG. 10 schematically depicts the microfluidic device of FIG. 8, in more detail;

[0150] FIG. 11 schematically depicts the microfluidic device of FIG. 5, in more detail, in use;

[0151] FIG. 12 is a graph showing results for microfluidic devices according to exemplary embodiments compared with a conventional microfluidic device;

[0152] FIG. 13A is a graph showing results for a conventional microfluidic device and FIG. 13B is a graph showing results for a microfluidic device according to exemplary embodiment; and

[0153] FIG. 14 is a graph showing results for microfluidic devices according to exemplary embodiments compared with conventional microfluidic devices.

DETAILED DESCRIPTION OF THE DRAWINGS

[0154] Generally, like reference signs indicate like features.

[0155] FIG. 1 schematically depicts a microfluidic device 100 according to an exemplary embodiment. Particularly, FIG. 1 shows a plan view of the microfluidic device 100.

[0156] Particularly, the microfluidic device 100 is for separating a liquid L into first and second liquid components L.sub.1, L.sub.2 thereof. The microfluidic device 100 comprises an inlet 130 for receiving the liquid therethrough. The microfluidic device 100 comprises a first outlet 110 for the first liquid component L.sub.1, wherein the first outlet 110 is fluidically coupled to the inlet 130 via a first passageway 140. The microfluidic device 100 comprises a second outlet 120 for the second liquid component L.sub.2, wherein the second outlet 120 is fluidically coupled to the first passageway 140 via a first set of N conduits 150 (150A, 150B, 150C), wherein N is a positive integer greater than 1, wherein respective conduits 150A, 150B, 150C of the first set of N conduits 150 divide from the first passageway 140 at respective divisions 152 (152A, 152B, 152C) from the inlet 130 therealong. The respective conduits 150A, 150B, 150C of the first set of N conduits 150 are arranged to, at least in part, equalize flowrate ratios at the respective divisions 152 (152A, 152B, 152C).

[0157] The first set of N conduits 150 consists of 3 conduits (i.e. N=3). The first conduit 150A is divided from the first passageway 140 at a spacing s.sub.A from the inlet 130 therealong, thereby providing the first division 152A, specifically a first bifurcation 152A. Similarly, the second conduit 150B is divided from the first passageway 140 at a spacing s.sub.B from the inlet 130 therealong, thereby providing the second division 152B, specifically a second bifurcation 152B. Similarly, the third conduit 150C is divided from the first passageway 140 at a spacing s.sub.C from the inlet 130 therealong, thereby providing the third division 152C, specifically a third bifurcation 152C.

[0158] The first passageway 140 is straight, having a length I, and has a constant circular cross-sectional area, having a diameter d. The first conduit 150A is straight, having a length l.sub.A, and has a constant circular cross-sectional area, having a diameter d.sub.A. The second conduit 150B is straight, having a length l.sub.B, and has a constant circular cross-sectional area, having a diameter d.sub.B. The third conduit 150C is straight, having a length l.sub.C, and has a constant circular cross-sectional area, having a diameter d.sub.C. The diameter d>>the diameter d.sub.C>the diameter d.sub.B >the diameter d.sub.A. The length l.sub.Athe length l.sub.C>the length l.sub.B.

[0159] Particularly, the respective conduits 150A, 150B, 150C of the first set of N conduits 150 are arranged to, at least in part, equalize flowrate ratios at the respective divisions 152 (152A, 152B, 152C) by having respective lengths l.sub.A, l.sub.B, l.sub.C and cross-sectional diameters d.sub.A, d.sub.B, d.sub.C (i.e. cross-sectional areas since circular) arranged to attenuate respective flowrates therethrough according to, at least in part, respective liquid pressures at the respective divisions 152 (152A, 152B, 152C), as described above.

[0160] The inlet 130, the first outlet 110 and the second outlet 120 are mutually equispaced, arranged in an equilateral triangle.

[0161] FIG. 2 schematically depicts a microfluidic device 200 according to an exemplary embodiment. Particularly, FIG. 2 shows a plan view of the microfluidic device 200.

[0162] FIG. 3 schematically depicts the microfluidic device 200 of FIG. 2, in more detail. Particularly, FIG. 3 shows an enlarged portion of region A of FIG. 2.

[0163] FIG. 4 schematically depicts the microfluidic device 200 of FIG. 2, in more detail. Particularly, FIG. 4 shows an enlarged portion of region B of FIG. 3.

[0164] Particularly, the microfluidic device 200 is for separating a liquid L into first and second liquid components L.sub.1, L.sub.2 thereof. The microfluidic device 200 comprises an inlet 230 for receiving the liquid therethrough. The microfluidic device 200 comprises a first outlet 210 for the first liquid component L.sub.1, wherein the first outlet 210 is fluidically coupled to the inlet 230 via a first passageway 240A. The microfluidic device 200 comprises a second outlet 220 for the second liquid component L.sub.2, wherein the second outlet 220 is fluidically coupled to the first passageway 240A via a first set of N conduits 250 (250A, 250B, 250C, 250D, 250E), wherein N is a positive integer greater than 1, wherein respective conduits 250A, 250B, 250C, 250D, 250E of the first set of N conduits 250 divide from the first passageway 240A at respective divisions 252 (252A, 252B, 252C, 252D, 252E) from the inlet 230 therealong. The respective conduits 250A, 250B, 250C, 250D, 250E of the first set of N conduits 250 are arranged to, at least in part, equalize flowrate ratios at the respective divisions 252 (252A, 252B, 252C, 252D, 252E).

[0165] The microfluidic device 200 is for separating whole blood. Preferably, the microfluidic device 200 is for separating diluted whole blood, for example whole blood diluted by a ratio of at most 10:1, preferably at most 5:1 more preferably at most 2:1, most preferably at most 1:1.

[0166] The first set of N conduits 250 consists of 5 conduits (i.e. N=5). The first conduit 250A is divided from the first passageway 240A at a spacing s.sub.A from the inlet 230 therealong, thereby providing the first division 252A, specifically a bifurcation 252A. Similarly, the second conduit 250B is divided the first passageway 240A at a spacing s.sub.B from the inlet 230 therealong, thereby providing the second division 252B, specifically a bifurcation 252B. Similarly, the third conduit 250C is divided from the first passageway 240A at a spacing s.sub.C from the inlet 230 therealong, thereby providing the third division 252C, specifically a bifurcation 252C. Similarly, the fourth conduit 250D is divided from the first passageway 240A at a spacing s.sub.D from the inlet 230 therealong, thereby providing the fourth division 252D, specifically a bifurcation 252D. Similarly, the fifth conduit 250E is divided from the first passageway 240A at a spacing s.sub.E from the inlet 230 therealong, thereby providing the fifth division 252E, specifically a bifurcation 252E.

[0167] In this example, the respective conduits 250A, 250B, 250C, 250D, 250E of the first set of N conduits 250 have respective lengths l.sub.A, l.sub.B, l.sub.C, l.sub.D, l.sub.E arranged to attenuate respective flowrates therethrough according to, at least in part, the respective liquid L pressure at the respective divisions 252 (252A, 252B, 252C, 252D, 252E). In this example, the length l.sub.A>the length l.sub.B >the length l.sub.C>the length l.sub.D>the length l.sub.E. In this example, the length l.sub.A is 6.75 mm, the length l.sub.B is 5.4 mm the length l.sub.C is 3.57 mm, the length l.sub.D is 2.16 mm and the length l.sub.E is 1.71 mm. In this example, the respective conduits 250A, 250B, 250C, 250D, 250E have the same constant rectangular cross-sectional areas, having respective equal widths d.sub.A, d.sub.B, d.sub.C, d.sub.D, d.sub.E of 15 m and respective equal heights of 20 m.

[0168] In this example, the first passageway 240A curves from the inlet towards the first outlet along a first part of a length thereof, wherein a first radius of curvature R1 of the first part is 10 mm. In this example, the first passageway 240A tapers along the first part of the length, from a width of 270 m to a width of 100 m over the first part of the length, wherein the first part of the length has a length of 15 mm. In this example, the first passageway 240A curves from the inlet towards the first outlet along a second part of a length thereof, wherein a second radius of curvature R2 of the second part is 1.3 mm. In this example, the first passageway 240A has a constant cross-sectional area along the second part of the length, having a constant width of 100 m. In this example, the first passageway 240A is linear along a third part of a length thereof, between the first part of the length and the second part of the length, wherein the first passageway 240A has a constant cross-sectional area along the third part of the length, having a constant width of 100 m. In this example, the first passageway 240A is arranged to surround, at least in part, the first set of N conduits 250.

[0169] In this example, the first passageway 240A comprises a set of constriction members 242 (242A, 242B, 242C, 242D, 242E), wherein respective constriction members 242A, 242B, 242C, 242D, 242E of the set of constriction members 242 correspond with the respective conduits 250A, 250B, 250C, 250D, 250E of the first set of N conduits 250. The respective constriction members 242A, 242B, 242C, 242D, 242E are arranged upstream (i.e. with respect to flow of the liquid L) of the respective conduits 250A, 250B, 250C, 250D, 250E. The respective constriction members 242A, 242B, 242C, 242D, 242E are arranged proximal to, and upstream of, the respective divisions 252A, 252B, 252C, 252D, 252E. In this example, the respective constriction members 242A, 242B, 242C, 242D, 242E of the set of constriction members 242 are similar. In this example, the respective constriction members 242A, 242B, 242C, 242D, 242E of the set of constriction members 242 have the same constant rectangular cross-sectional areas, having respective equal widths d.sub.con of 38 m, heights of 20 m and lengths of 0.302 mm.

[0170] In this example, the first passageway 240A comprises a set of expansion members 244 (244A, 244B, 244C, 244D), wherein respective expansion members 244A, 244B, 244C, 244D of the set of expansion members 240A correspond with the respective conduits 250A, 250B, 250C, 250D of the first set of N conduits 250. The respective expansion members 244A, 244B, 244C, 244D are arranged downstream (i.e. with respect to flow of the liquid L) of the respective conduits 250A, 250B, 250C, 250D. The respective expansion members 244A, 244B, 244C, 244D are arranged proximal to, and downstream of, the respective divisions 252A, 252B, 252C, 252D. In this example, the respective expansion members 244A, 244B, 244C, 244D of the set of expansion members 240A are similar. In this example, the respective expansion members 244A, 244B, 244C, 244D of the set of expansion members 240A have the same rectangular cross-sectional areas, having respective equal widths d.sub.exp of 153 m and heights of 20 m. An expansion member is not provided corresponding with the last conduit 250E of the first set of N conduits 250.

[0171] In this example, the conduit 250A of the first set of N conduits 250 is arranged at an acute angle .sub.A to the first passageway 240. In this example, the acute angle .sub.A is approximately 45. The respective conduits 250B, 250C, 250D, 250E of the first set of N conduits 250 are arranged similarly at respective acute angles .sub.B, .sub.C, .sub.D, .sub.E to the first passageway 240, in which the angle .sub.A=.sub.B=.sub.C=.sub.D=.sub.E.

[0172] In this example, the first passageway 240A defines a linear flow path of the liquid via the respective divisions, wherein a wall, for example opposed to the first set of N conduits 250, of the first passageway 240A extending between the respective divisions 252 is linear.

[0173] In this example, the conduit 250A of the first set of N conduits 250 is arranged boustrophedonically, having three parallel legs 254A of equal lengths b.sub.A. In this example, the conduit 250B of the first set of N conduits 250 is arranged boustrophedonically, having three parallel legs 254B of equal lengths b.sub.B. In this example, the conduit 250C of the first set of N conduits 250 is arranged boustrophedonically, having three parallel legs 254C of equal lengths b.sub.C. In this example, the length b.sub.A>the length b.sub.B>the length b.sub.C. In this example, the conduits 250D, 250E of the first set of N conduits 250 are not arranged boustrophedonically.

[0174] In this example, the inlet 230, the first outlet 210 and the second outlet 220 are arranged collinearly, thereby defining an axis Y.

[0175] In this example, the first outlet 210 is fluidically coupled to the inlet 230 via a second passageway 240B. In this example, the second 220 outlet is fluidically coupled to the second passageway 240B via a second set of M conduits 250 (250F, 250G, 250H, 250I, 250J), wherein M is a positive integer greater than 1, wherein respective conduits of the second set of M conduits 250 (250F, 250G, 250H, 250I, 250J) divide from the second passageway 240B at respective divisions 252 (252F, 252G, 252H, 252I, 252J) from the inlet 230 therealong. In this example, the respective conduits of the second set of M conduits 250 (250F, 250G, 250H, 250I, 250J) are arranged to, at least in part, equalize flowrate ratios at the respective divisions 252 (252F, 252G, 252H, 252I, 252J).

[0176] The second passageway 240B and the second set of M conduits 250 (250F, 250G, 250H, 250I, 250J) are as described with respect to the first passageway 240A and the first set of N conduits 250 (250A, 250B, 250C, 250D, 250E), respectively. In this example, N and M are equal to five.

[0177] In this example, the microfluidic device 200 comprises a first outlet passageway 260A fluidically coupled to the second outlet 220 and to the first set of N conduits 250 (250A, 250B, 250C, 250D, 250E), wherein the second outlet 220 is fluidically coupled to the first passageway 240A via the first set of N conduits 250 (250A, 250B, 250C, 250D, 250E) and the first outlet passageway 260A.

[0178] In this example, the microfluidic device 200 comprises a second outlet passageway 260B fluidically coupled to the second outlet 220 and to the second set of M conduits 250 (250F, 250G, 250H, 250I, 250J), wherein the second outlet 220 is fluidically coupled to the second passageway 240B via the second set of M conduits 250 (250F, 250G, 250H, 250I, 250J) and the second outlet passageway 260B.

[0179] In this example, the first passageway 240A and the first set of N conduits 250 (250A, 250B, 250C, 250D, 250E) are arranged symmetrically about the axis Y with respect to the second passageway 240B and the second set of M conduits 250 (250F, 250G, 250H, 250I, 250J). The second passageway 240B is a reflection of the first passageway 240A, in which the axis Y is a mirror line, thereby defining a heart-shape. The respective conduits 250F, 250G, 250H, 250I, 250J are respective reflections of the respective conduits 250A, 250B, 250C, 250D, 250E, in which the axis Y is the mirror line.

[0180] In this example, the microfluidic device 200 is provided on a rectangular lab-on-a-chip device 20, having four (4) apertures 21A, 21B, 21C, 21D therethrough provided at corners thereof for securing in use. Alternative methods of securing in use are known.

[0181] FIG. 5 schematically depicts a microfluidic device 300 according to an exemplary embodiment. Particularly, FIG. 5 shows a plan view of the microfluidic device 300.

[0182] FIG. 6 schematically depicts the microfluidic device 300 of FIG. 5, in more detail. Particularly, FIG. 3 shows an enlarged portion of region A of FIG. 5.

[0183] FIG. 7 schematically depicts the microfluidic device 300 of FIG. 5, in more detail. Particularly, FIG. 7 shows an enlarged portion of region B of FIG. 6.

[0184] Particularly, the microfluidic device 300 is for separating a liquid L into first and second liquid components L.sub.1, L.sub.2 thereof. The microfluidic device 300 comprises an inlet 330 for receiving the liquid therethrough. The microfluidic device 300 comprises a first outlet 310 for the first liquid component L.sub.1, wherein the first outlet 310 is fluidically coupled to the inlet 330 via a first passageway 340A. The microfluidic device 300 comprises a second outlet 320 for the second liquid component L.sub.2, wherein the second outlet 320 is fluidically coupled to the first passageway 340A via a first set of N conduits 350 (350A, 350B, 350C, 350D, 350E), wherein N is a positive integer greater than 1, wherein respective conduits 350A, 350B, 350C, 350D, 350E of the first set of N conduits 350 divide from the first passageway 340A at respective divisions 352 (352A, 352B, 352C, 352D, 352E) from the inlet 330 therealong. The respective conduits 350A, 350B, 350C, 350D, 350E of the first set of N conduits 350 are arranged to, at least in part, equalize flowrate ratios at the respective divisions 352 (352A, 352B, 352C, 352D, 352E).

[0185] Generally, the microfluidic device 300 is as described with respect to the microfluidic device 200.

[0186] The microfluidic device 300 is for separating whole blood. Preferably, the microfluidic device 300 is for separating diluted whole blood, for example whole blood diluted by a ratio of at most 10:1, preferably at most 5:1 more preferably at most 3:1, most preferably at most 1:1.

[0187] The first set of N conduits 350 consists of 5 conduits (i.e. N=5). The first conduit 350A is divided from the first passageway 340A at a spacing s.sub.A from the inlet 330 therealong, thereby providing the first division 352A, specifically a bifurcation 352A. Similarly, the second conduit 350B is divided the first passageway 340A at a spacing s.sub.B from the inlet 330 therealong, thereby providing the second division 352B, specifically a bifurcation 352B. Similarly, the third conduit 350C is divided from the first passageway 340A at a spacing s.sub.C from the inlet 330 therealong, thereby providing the third division 352C, specifically a bifurcation 352C. Similarly, the fourth conduit 350D is divided from the first passageway 340A at a spacing s.sub.D from the inlet 330 therealong, thereby providing the fourth division 352D, specifically a bifurcation 352D. Similarly, the fifth conduit 350E is divided from the first passageway 340A at a spacing s.sub.E from the inlet 330 therealong, thereby providing the fifth division 352E, specifically a bifurcation 352E.

[0188] In this example, the respective conduits 350A, 350B, 350C, 350D, 350E of the first set of N conduits 350 have respective lengths l.sub.A, l.sub.B, l.sub.C, l.sub.D, l.sub.E arranged to attenuate respective flowrates therethrough according to, at least in part, the respective liquid L pressure at the respective divisions 352 (352A, 352B, 352C, 352D, 352E). In this example, the length l.sub.A>the length l.sub.B>the length l.sub.C>the length l.sub.D>the length l.sub.E. In this example, the length l.sub.A is 6.75 mm, the length l.sub.B is 5.4 mm the length l.sub.C is 3.57 mm, the length l.sub.D is 2.16 mm and the length l.sub.E is 1.71 mm. In this example, the respective conduits 350A, 350B, 350C, 350D, 350E have the same constant rectangular cross-sectional areas, having respective equal widths d.sub.A, d.sub.B, d.sub.C, d.sub.D, d.sub.E of 15 m and respective equal heights of 20 m.

[0189] In this example, the first passageway 340A curves from the inlet towards the first outlet along a first part of a length thereof, wherein a first radius of curvature R1 of the first part is 10 mm. In this example, the first passageway 340A tapers along the first part of the length, from a width of 370 m to a width of 100 m over the first part of the length, wherein the first part of the length has a length of 15 mm. In this example, the first passageway 340A curves from the inlet towards the first outlet along a second part of a length thereof, wherein a second radius of curvature R2 of the second part is 1.3 mm. In this example, the first passageway 340A has a constant cross-sectional area along the second part of the length, having a constant width of 100 m. In this example, the first passageway 340A is linear along a third part of a length thereof, between the first part of the length and the second part of the length, wherein the first passageway 340A has a constant cross-sectional area along the third part of the length, having a constant width of 100 m. In this example, the first passageway 340A is arranged to surround, at least in part, the first set of N conduits 350.

[0190] In this example, the first passageway 340A comprises a set of constriction members 342 (342A, 342B, 342C, 342D, 342E), wherein respective constriction members 342A, 342B, 342C, 342D, 342E of the set of constriction members 342 correspond with the respective conduits 350A, 350B, 350C, 350D, 350E of the first set of N conduits 350. The respective constriction members 342A, 342B, 342C, 342D, 342E are arranged upstream (i.e. with respect to flow of the liquid L) of the respective conduits 350A, 350B, 350C, 350D, 350E. The respective constriction members 342A, 342B, 342C, 342D, 342E are arranged proximal to, and upstream of, the respective divisions 352A, 352B, 352C, 352D, 352E. In this example, the respective constriction members 342A, 342B, 342C, 342D, 342E of the set of constriction members 342 are similar. In this example, the respective constriction members 342A, 342B, 342C, 342D, 342E of the set of constriction members 342 have the same constant rectangular cross-sectional areas, having respective equal widths d.sub.con of 38 m, heights of 20 m and lengths of 0.302 mm.

[0191] In this example, the first passageway 340A comprises a set of expansion members 344 (344A, 344B, 344C, 344D, 344E), wherein respective expansion members 344A, 344B, 344C, 344D, 344E of the set of expansion members 340A correspond with the respective conduits 350A, 350B, 350C, 350D, 350E of the first set of N conduits 350. The respective expansion members 344A, 344B, 344C, 344D, 344E are arranged downstream (i.e. with respect to flow of the liquid L) of the respective conduits 350A, 350B, 350C, 350D, 350E. The respective expansion members 344A, 344B, 344C, 344D, 344E are arranged proximal to, and downstream of, the respective divisions 352A, 352B, 352C, 352D, 352E. In this example, the respective expansion members 344A, 344B, 344C, 344D, 344E of the set of expansion members 340A are similar. In this example, the respective expansion members 344A, 344B, 344C, 344D, 344E of the set of expansion members 340A have the same non-constant rectangular cross-sectional areas, having widths that enlarge smoothly and arcuately away from the respective divisions 352A, 352B, 352C, 352D, 352E to respective maximum widths d.sub.exp and reduce smoothly and arcuately thereafter towards the respective constriction members 342A, 342B, 342C, 342D, 342E.

[0192] In this example, the conduit 350A of the first set of N conduits 350 is arranged at an acute angle .sub.A to the first passageway 340. In this example, the acute angle .sub.A is approximately 45. The respective conduit 350B, 350C, 350D, 350E of the first set of N conduits 350 are arranged similarly at respective acute angles .sub.B, .sub.C, .sub.D, .sub.E to the first passageway 340, in which the angle .sub.A=.sub.B=.sub.C=.sub.D=.sub.E.

[0193] In this example, the first passageway 340A defines a non-linear flow path of the liquid via the respective divisions, wherein a wall, for example opposed to the first set of N conduits 350, of the first passageway 340A extending between the respective divisions 352 is non-linear. Particularly, the wall, opposed to the first set of N conduits 350, of the first passageway 340A extending between the respective divisions 352 comprises alternating linear parts through the constriction members 342 (342A, 342B, 342C, 342D, 342E) and smoothly curved parts through the expansion members 344 (344A, 344B, 344C, 344D, 344E) therebetween, in which the smoothly curved parts are similar.

[0194] In this example, the conduit 350A of the first set of N conduits 350 is arranged boustrophedonically, having three parallel legs 354A of equal lengths b.sub.A. In this example, the conduit 350B of the first set of N conduits 350 is arranged boustrophedonically, having three parallel legs 354B of equal lengths b.sub.B. In this example, the conduit 350C of the first set of N conduits 350 is arranged boustrophedonically, having three parallel legs 354C of equal lengths b.sub.C. In this example, the conduit 350D of the first set of N conduits 350 is arranged boustrophedonically, having three parallel legs 354D of equal lengths b.sub.D. In this example, the conduit 350E of the first set of N conduits 350 is arranged boustrophedonically, having three parallel legs 354E of equal lengths b.sub.E. In this example, the length b.sub.A>the length b.sub.B>the length b.sub.C>the length b.sub.D>the length b.sub.E.

[0195] In this example, the inlet 330, the first outlet 310 and the second outlet 320 are arranged collinearly, thereby defining an axis Y.

[0196] In this example, the first outlet 310 is fluidically coupled to the inlet 330 via a second passageway 340B. In this example, the second 320 outlet is fluidically coupled to the second passageway 340B via a second set of M conduits 350 (350F, 350G, 350H, 350I, 350J), wherein M is a positive integer greater than 1, wherein respective conduits of the second set of M conduits 350 (350F, 350G, 350H, 350I, 350J) divide from the second passageway 340B at respective divisions 352 (352F, 352G, 352H, 352I, 352J) from the inlet 330 therealong. In this example, the respective conduits of the second set of M conduits 350 (350F, 350G, 350H, 350I, 350J) are arranged to, at least in part, equalize flowrate ratios at the respective divisions 352 (352F, 352G, 352H, 352I, 352J).

[0197] The second passageway 340B and the second set of M conduits 350 (350F, 350G, 350H, 350I, 350J) are as described with respect to the first passageway 340A and the first set of N conduits 350 (350A, 350B, 350C, 350D, 350E), respectively. In this example, N and M are equal to five.

[0198] In this example, the microfluidic device 300 comprises a first outlet passageway 360A fluidically coupled to the second outlet 320 and to the first set of N conduits 350 (350A, 350B, 350C, 350D, 350E), wherein the second outlet 320 is fluidically coupled to the first passageway 340A via the first set of N conduits 350 (350A, 350B, 350C, 350D, 350E) and the first outlet passageway 360A.

[0199] In this example, the microfluidic device 300 comprises a second outlet passageway 360B fluidically coupled to the second outlet 320 and to the second set of M conduits 350 (350F, 350G, 350H, 350I, 350J), wherein the second outlet 320 is fluidically coupled to the second passageway 340B via the second set of M conduits 350 (350F, 350G, 350H, 350I, 350J) and the second outlet passageway 360B.

[0200] In this example, the first passageway 340A and the first set of N conduits 350 (350A, 350B, 350C, 350D, 350E) are arranged symmetrically about the axis Y with respect to the second passageway 340B and the second set of M conduits 350 (350F, 350G, 350H, 350I, 350J). The second passageway 340B is a reflection of the first passageway 340A, in which the axis Y is a mirror line, thereby defining a heart-shape. The respective conduits 350F, 350G, 350H, 350I, 350J are respective reflections of the respective conduits 350A, 350B, 350C, 350D, 350E, in which the axis Y is the mirror line.

[0201] In this example, the microfluidic device 300 is provided on a rectangular lab-on-a-chip device 30, having four (4) apertures 31A, 31B, 31C, 31D therethrough provided at corners thereof for securing in use. Alternative methods of securing in use are known.

[0202] FIG. 8 schematically depicts a microfluidic device 400 according to an exemplary embodiment. Particularly, FIG. 8 shows a plan view of the microfluidic device 400.

[0203] FIG. 9 schematically depicts the microfluidic device 400 of FIG. 8, in more detail. Particularly, FIG. 9 shows an enlarged portion of region A of FIG. 8.

[0204] FIG. 10 schematically depicts the microfluidic device 400 of FIG. 8, in more detail. Particularly, FIG. 10 shows an enlarged portion of region B of FIG. 9.

[0205] Particularly, the microfluidic device 400 is for separating a liquid L into first and second liquid components L.sub.1, L.sub.2 thereof. The microfluidic device 400 comprises an inlet 430 for receiving the liquid therethrough. The microfluidic device 400 comprises a first outlet 410 for the first liquid component L.sub.1, wherein the first outlet 410 is fluidically coupled to the inlet 430 via a first passageway 440A. The microfluidic device 400 comprises a second outlet 420 for the second liquid component L.sub.2, wherein the second outlet 420 is fluidically coupled to the first passageway 440A via a first set of N conduits 450 (450A, 450B, 450C, 450D, 450E), wherein N is a positive integer greater than 1, wherein respective conduits 450A, 450B, 450C, 450D, 450E of the first set of N conduits 450 divide from the first passageway 440A at respective divisions 452 (452A, 452B, 452C, 452D, 452E) from the inlet 430 therealong. The respective conduits 450A, 450B, 450C, 450D, 450E of the first set of N conduits 450 are arranged to, at least in part, equalize flowrate ratios at the respective divisions 452 (452A, 452B, 452C, 452D, 452E).

[0206] Generally, the microfluidic device 400 is as described with respect to the microfluidic device 200.

[0207] The microfluidic device 400 is for separating whole blood. Preferably, the microfluidic device 400 is for separating diluted whole blood, for example whole blood diluted by a ratio of at most 10:1, preferably at most 5:1 more preferably at most 4:1, most preferably at most 1:1.

[0208] The first set of N conduits 450 consists of 5 conduits (i.e. N=5). The first conduit 450A is divided from the first passageway 440A at a spacing s.sub.A from the inlet 430 therealong, thereby providing the first division 452A, specifically a bifurcation 452A. Similarly, the second conduit 450B is divided the first passageway 440A at a spacing s.sub.B from the inlet 430 therealong, thereby providing the second division 452B, specifically a bifurcation 452B. Similarly, the third conduit 450C is divided from the first passageway 440A at a spacing s.sub.C from the inlet 430 therealong, thereby providing the third division 452C, specifically a bifurcation 452C. Similarly, the fourth conduit 450D is divided from the first passageway 440A at a spacing s.sub.D from the inlet 430 therealong, thereby providing the fourth division 452D, specifically a bifurcation 452D.

[0209] Similarly, the fifth conduit 450E is divided from the first passageway 440A at a spacing s.sub.E from the inlet 430 therealong, thereby providing the fifth division 452E, specifically a bifurcation 452E.

[0210] In this example, the respective conduits 450A, 450B, 450C, 450D, 450E of the first set of N conduits 450 have respective lengths l.sub.A, l.sub.B, l.sub.C, l.sub.D, l.sub.E arranged to attenuate respective flowrates therethrough according to, at least in part, the respective liquid L pressure at the respective divisions 452 (452A, 452B, 452C, 452D, 452E) 452 (452A, 452B, 452C, 452D, 452E). In this example, the length l.sub.A>the length l.sub.B>the length l.sub.C>the length l.sub.D>the length l.sub.E. In this example, the length l.sub.A is 6.75 mm, the length l.sub.B is 5.4 mm the length l.sub.C is 3.57 mm, the length l.sub.D is 2.16 mm and the length l.sub.E is 1.71 mm. In this example, the respective conduits 450A, 450B, 450C, 450D, 450E have the same constant rectangular cross-sectional areas, having respective equal widths d.sub.A, d.sub.B, d.sub.C, d.sub.D, d.sub.E of 15 m and respective equal heights of 20 m.

[0211] In this example, the first passageway 440A curves from the inlet towards the first outlet along a first part of a length thereof, wherein a first radius of curvature R1 of the first part is 10 mm. In this example, the first passageway 440A tapers along the first part of the length, from a width of 470 m to a width of 100 m over the first part of the length, wherein the first part of the length has a length of 15 mm. In this example, the first passageway 440A curves from the inlet towards the first outlet along a second part of a length thereof, wherein a second radius of curvature R2 of the second part is 1.3 mm. In this example, the first passageway 440A has a constant cross-sectional area along the second part of the length, having a constant width of 100 m. In this example, the first passageway 440A is linear along a third part of a length thereof, between the first part of the length and the second part of the length, wherein the first passageway 440A has a constant cross-sectional area along the third part of the length, having a constant width of 100 m. In this example, the first passageway 440A is arranged to surround, at least in part, the first set of N conduits 450.

[0212] In this example, the first passageway 440A comprises a set of constriction members 442 (442A, 442B, 442C, 442D, 442E), wherein respective constriction members 442A, 442B, 442C, 442D, 442E of the set of constriction members 442 correspond with the respective conduits 450A, 450B, 450C, 450D, 450E of the first set of N conduits 450. The respective constriction members 442A, 442B, 442C, 442D, 442E are arranged upstream (i.e. with respect to flow of the liquid L) of the respective conduits 450A, 450B, 450C, 450D, 450E. The respective constriction members 442A, 442B, 442C, 442D, 442E are arranged proximal to, and upstream of, the respective divisions 452A, 452B, 452C, 452D, 452E. In this example, the respective constriction members 442A, 442B, 442C, 442D, 442E of the set of constriction members 442 are similar. In this example, the respective constriction members 442A, 442B, 442C, 442D, 442E of the set of constriction members 442 have the same constant rectangular cross-sectional areas, having respective equal widths d.sub.con of 38 m, heights of 20 m and lengths of 0.302 mm.

[0213] In this example, the first passageway 440A comprises a set of expansion members 444 (444A, 444B, 444C, 444D, 444E), wherein respective expansion members 444A, 444B, 444C, 444D, 444E of the set of expansion members 440A correspond with the respective conduits 450A, 450B, 450C, 450D, 450E of the first set of N conduits 450. The respective expansion members 444A, 444B, 444C, 444D, 444E are arranged downstream (i.e. with respect to flow of the liquid L) of the respective conduits 450A, 450B, 450C, 450D, 450E. The respective expansion members 444A, 444B, 444C, 444D, 444E are arranged proximal to, and downstream of, the respective divisions 452A, 452B, 452C, 452D, 452E. In this example, the respective expansion members 444A, 444B, 444C, 444D, 444E of the set of expansion members 440A are similar. In this example, the respective expansion members 444A, 444B, 444C, 444D, 444E of the set of expansion members 440A have the same non-constant rectangular cross-sectional areas, having widths that enlarge smoothly and arcuately away from the respective divisions 452A, 452B, 452C, 452D, 452E to respective maximum widths d.sub.exp and reduce smoothly and arcuately thereafter towards the respective constriction members 442A, 442B, 442C, 442D, 442E.

[0214] In this example, the conduit 450A of the first set of N conduits 450 is arranged at an acute angle .sub.A to the first passageway 440. In this example, the acute angle .sub.A is approximately 45. The respective conduit 450B, 450C, 450D, 450E of the first set of N conduits 450 are arranged similarly at respective acute angles .sub.B, .sub.C, .sub.D, .sub.E to the first passageway 440, in which the angle .sub.A=.sub.C=.sub.D=.sub.D=.sub.E.

[0215] In this example, the first passageway 440A defines a stepped linear flow path of the liquid via the respective divisions, wherein a wall, for example adjacent to the first set of N conduits 450, of the first passageway 440A extending between the respective divisions 452 is stepped. Particularly, the wall, adjacent to the first set of N conduits 450, of the first passageway 440A extending between the respective divisions 452 comprises linear parts through the constriction members 442 (442A, 442B, 442C, 442D, 442E) and through the expansion members 444 (444A, 444B, 444C, 444D, 444E) therebetween, in which the successive linear parts are stepped at the respect divisions. In contrast, an opposed wall, opposed to the first set of N conduits 450, of the first passageway 440A extending between the respective divisions 452 comprises alternating linear parts through the constriction members 442 (442A, 442B, 442C, 442D, 442E) and smoothly curved parts through the expansion members 444 (444A, 444B, 444C, 444D, 444E) therebetween, in which the smoothly curved parts are similar.

[0216] In this example, the conduit 450A of the first set of N conduits 450 is arranged boustrophedonically, having three parallel legs 454A of equal lengths b.sub.A. In this example, the conduit 450B of the first set of N conduits 450 is arranged boustrophedonically, having three parallel legs 454B of equal lengths b.sub.B. In this example, the conduit 450C of the first set of N conduits 450 is arranged boustrophedonically, having three parallel legs 454C of equal lengths b.sub.C. In this example, the length b.sub.A>the length b.sub.B>the length b.sub.C. In this example, the conduits 450D, 450E of the first set of N conduits 450 are not arranged boustrophedonically.

[0217] In this example, the inlet 430, the first outlet 410 and the second outlet 420 are arranged collinearly, thereby defining an axis Y.

[0218] In this example, the first outlet 410 is fluidically coupled to the inlet 430 via a second passageway 440B. In this example, the second 420 outlet is fluidically coupled to the second passageway 440B via a second set of M conduits 450 (450F, 450G, 450H, 450I, 450J), wherein M is a positive integer greater than 1, wherein respective conduits of the second set of M conduits 450 (450F, 450G, 450H, 450I, 450J) divide from the second passageway 440B at respective divisions 452 (452F, 452G, 452H, 452I, 452J) from the inlet 430 therealong. In this example, the respective conduits of the second set of M conduits 450 (450F, 450G, 450H, 450I, 450J) are arranged to, at least in part, equalize flowrate ratios at the respective divisions 452 (452F, 452G, 452H, 452I, 452J).

[0219] The second passageway 440B and the second set of M conduits 450 (450F, 450G, 450H, 450I, 450J) are as described with respect to the first passageway 440A and the first set of N conduits 450 (450A, 450B, 450C, 450D, 450E), respectively. In this example, N and M are equal, to five.

[0220] In this example, the microfluidic device 400 comprises a first outlet passageway 460A fluidically coupled to the second outlet 420 and to the first set of N conduits 450 (450A, 450B, 450C, 450D, 450E), wherein the second outlet 420 is fluidically coupled to the first passageway 440A via the first set of N conduits 450 (450A, 450B, 450C, 450D, 450E) and the first outlet passageway 460A.

[0221] In this example, the microfluidic device 400 comprises a second outlet passageway 460B fluidically coupled to the second outlet 420 and to the second set of M conduits 450 (450F, 450G, 450H, 450I, 450J), wherein the second outlet 420 is fluidically coupled to the second passageway 440B via the second set of M conduits 450 (450F, 450G, 450H, 450I, 450J) and the second outlet passageway 460B.

[0222] In this example, the first passageway 440A and the first set of N conduits 450 (450A, 450B, 450C, 450D, 450E) are arranged symmetrically about the axis Y with respect to the second passageway 440B and the second set of M conduits 450 (450F, 450G, 450H, 450I, 450J). The second passageway 440B is a reflection of the first passageway 440A, in which the axis Y is a mirror line, thereby defining a heart-shape. The respective conduits 450F, 450G, 450H, 450I, 450J are respective reflections of the respective conduits 450A, 450B, 450C, 450D, 450E, in which the axis Y is the mirror line.

[0223] In this example, the microfluidic device 400 is provided on a rectangular lab-on-a-chip device 40, having four (4) apertures 41A, 41B, 41C, 41D therethrough provided at corners thereof for securing in use. Alternative methods of securing in use are known.

[0224] FIG. 11 schematically depicts the microfluidic device 300 of FIG. 5, in more detail, in use. Particularly, FIG. 11 is a photograph of the microfluidic device 300 showing the division 352A during separation of plasma (i.e. the second liquid component L.sub.2) from blood (i.e the liquid L). A width W of a cell-free layer at the division 352A is approximately 30 m.

[0225] FIG. 12 is a graph showing results for microfluidic devices according to exemplary embodiments compared with a conventional microfluidic device. Particularly, the graph shows flow rate ratios between a first passageway and successive conduits of a first set of N conduits at each division, obtained from Computational Fluid Dynamics (CFD) simulations, for microfluidic devices according to the exemplary embodiments (squares and triangles) compared with the conventional microfluidic device (circles). For the microfluidic devices according to the exemplary embodiments (squares and triangles), 4 bifurcations were provided on one side of the first passageway and thus the bifurcation numbers are 1, 2, 3 and 4. For the conventional microfluidic device (circles), 8 bifurcations were staggered on alternate sides, including at intermediate spacings and thus the bifurcation numbers are 1, 1.5, 2, 2.5, 3, 3.5, 4 and 4.5. The first set of N conduits of the conventional microfluidic device are not arranged to, at least in part, equalize flowrate ratios at the respective divisions, having equal respective fluidic resistances provided by the respective conduits having equal respective lengths, cross-sectional areas and cross-sectional shapes. The flow rate ratios for the microfluidic devices according to the exemplary embodiments (squares and triangles) are relatively more constant than for the conventional microfluidic device (circles).

[0226] FIG. 13A is a graph showing results for a conventional microfluidic device and FIG. 13B is a graph showing results for a microfluidic device according to exemplary embodiment. Particularly, the graphs show the effects of input flow rates (circles: 5 ml/h; triangles: 10 ml/h) on widths of cell-free zones at respective divisions (labelled as constriction number) for separation of blood (diluted 1:1). Insets show photographs of the first division of each of the microfluidic devices at input flow rates 10 ml/h. Error bars denote SD, n=3, except single data points for the conventional microfluidic device at 5 ml/h. For the microfluidic device according to the exemplary embodiment, the indicated flow rate values denote branch flow rates, inlet flow rates are two times higher. For the conventional fluidic device, a width of the cell-free layer is within approximatively 20% of the maximum cell-free zones (FIG. 13A). In contrast, for the microfluidic device according to the exemplary embodiment, the width of the cell-free layer is reduced to within approximatively 10% of the maximum cell-free zones (FIG. 13B).

[0227] FIG. 14 is a graph showing results for microfluidic devices according to exemplary embodiments compared with a conventional microfluidic device. Particularly, the graph shows failure rates of the microfluidic devices according to the exemplary embodiments (labelled as Mar15 D1, Mar15 D2 and Mar15 D3) compared with the conventional microfluidic device (labelled as Nov09). Failure is defined as a pump stall event prior to emptying a 3 mL syringe through the respective microfluidic devices. A ratio of failed separations to all separations is indicated above the columns. The data are compiled from various experiments for blood. Dilution was 1:1 for Mar15 D1 & D3 and Nov09, while dilutions were from 1:3 to 1:10 for Mar15 D2. Inlet flow rates ranged from 10 to 20 ml/h. The lower failure rates may be at least partly attributed to the respective intersections of the respective conduits and the first passageway at the respective divisions defining arcuate flow paths of the second liquid component, as described previously.

[0228] Although a preferred embodiment has been shown and described, it will be appreciated by those skilled in the art that various changes and modifications might be made without departing from the scope of the invention, as defined in the appended claims and as described above.

[0229] In summary, the invention provides a microfluidic device for separating a liquid into first and second liquid components thereof at an improved throughput, such as at a higher flowrate and/or a higher pressure of the liquid, at improved yields and/or purities of the separated first and second liquid components. The microfluidic device is suitable for inline processing, such as on lab-on-a-chip devices. The microfluidic device is suitable for separating biological fluids, for example whole blood into plasma and waste.

[0230] Attention is directed to all papers and documents which are filed concurrently with or previous to this specification in connection with this application and which are open to public inspection with this specification, and the contents of all such papers and documents are incorporated herein by reference.

[0231] All of the features disclosed in this specification (including any accompanying claims and drawings), and/or all of the steps of any method or process so disclosed, may be combined in any combination, except combinations where at most some of such features and/or steps are mutually exclusive.

[0232] Each feature disclosed in this specification (including any accompanying claims, and drawings) may be replaced by alternative features serving the same, equivalent or similar purpose, unless expressly stated otherwise. Thus, unless expressly stated otherwise, each feature disclosed is one example only of a generic series of equivalent or similar features.

[0233] The invention is not restricted to the details of the foregoing embodiment(s). The invention extends to any novel one, or any novel combination, of the features disclosed in this specification (including any accompanying claims and drawings), or to any novel one, or any novel combination, of the steps of any method or process so disclosed.