External material accession systems and methods
First Claim
Patent Images
1. A method of sampling a first fluid, comprising:
- (a) dipping an open end of an open ended fluid-filled capillary element into a source of the first fluid;
(b) withdrawing the capillary element from the first fluid;
(c) permitting an amount of the first fluid remaining on the open ended capillary to spontaneously inject into the capillary channel, thereby injecting the first fluid into the capillary channel;
(d) dipping the capillary element into a second fluid after a first selected time period, the first selected time period being controlled to control the amount of the first fluid permitted to spontaneously inject into the open ended capillary channel.
2 Assignments
0 Petitions
Accused Products
Abstract
Methods, apparatus and systems are provided for introducing large numbers of different materials into a microfluidic analytical device rapidly, efficiently and reproducibly. In particular, improved integrated pipettor chip configurations, e.g. sippers or electropipettors, are described which are capable of sampling extremely small amounts of material for which analysis is desired, transporting material into a microfluidic analytical channel network, and performing the desired analysis on the material.
194 Citations
96 Claims
-
1. A method of sampling a first fluid, comprising:
-
(a) dipping an open end of an open ended fluid-filled capillary element into a source of the first fluid;
(b) withdrawing the capillary element from the first fluid;
(c) permitting an amount of the first fluid remaining on the open ended capillary to spontaneously inject into the capillary channel, thereby injecting the first fluid into the capillary channel;
(d) dipping the capillary element into a second fluid after a first selected time period, the first selected time period being controlled to control the amount of the first fluid permitted to spontaneously inject into the open ended capillary channel. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35)
dipping the open end of the capillary element into a source of a third fluid after dipping the capillary into the source of second fluid;
withdrawing the capillary from the third fluid;
permitting an amount of the third fluid remaining on the open ended capillary to spontaneously inject into the capillary channel;
dipping the capillary into the second fluid after a second selected time period, the second selected time period being controlled to control the amount of the third fluid permitted to spontaneously inject into the open ended capillary channel.
-
-
3. The method of claim 1, further comprising transporting the amount of first fluid through the capillary for a second selected time, the second selected time being selected to control an amount of dilution of the amount of first fluid.
-
4. The method of claim 3, wherein the second selected time is controlled by controlling a flow rate of the amount of the first fluid through the capillary.
-
5. The method of claim 3, wherein the second selected time is controlled by selecting at least one of a length or a diameter of the capillary channel.
-
6. The method of claim 1, further comprising applying an electric field along a length of the capillary channel to electrokinetically transport the first fluid through the capillary channel.
-
7. The method of claim 1, further comprising applying pressure along the length of the capillary channel to transport the first fluid through the capillary channel.
-
8. The method of claim 1, further comprising introducing an amount of a low salt buffer into the capillary channel before injecting the amount of first fluid into the capillary channel.
-
9. The method of claim 1, further comprising introducing an amount of low salt buffer fluid into the capillary channel after injecting the amount of first fluid into the capillary channel.
-
10. The method of claim 1, further comprising introducing an amount of a high salt buffer into the capillary channel before injecting the amount of first fluid into the capillary channel.
-
11. The method of claim 1, further comprising introducing an amount of high salt buffer fluid into the capillary channel after injecting the amount of first fluid into the capillary channel.
-
12. The method of claim 1, further comprising introducing an amount of air into the capillary channel before injecting the amount of first fluid into the capillary channel.
-
13. The method of claim 1, further comprising introducing an amount of air into the capillary channel after injecting the amount of first fluid into the capillary channel.
-
14. The method of claim 1, further comprising introducing an amount of immiscible fluid into the capillary channel before injecting the amount of first fluid into the capillary channel.
-
15. The method of claim 1, further comprising introducing an amount of immiscible fluid into the capillary channel after injecting the amount of first fluid into the capillary channel.
-
16. The method of claim 1, wherein the first fluid comprises a first test compound.
-
17. The method of claim 1, further comprising repeating steps (a)-(d) with a plurality of separate fluid sources, each of the separate fluid sources comprising a different test compound.
-
18. The method of claim 1, wherein the plurality of different fluid sources comprises at least 1000 separate fluid sources, each separate fluid source comprising a different test compound.
-
19. The method of claim 18, wherein at least one of the at least 1000 separate sources comprises an inactivating compound.
-
20. The method of claim 1, wherein the first fluid comprises a nonaqueous fluid.
-
21. The method of claim 20, wherein the nonaqueous fluid comprises DMSO, DMF, acetone or an alcohol.
-
22. The method of claim 20, wherein the amount of first fluid injected into the capillary channel is less than 1 μ
- l.
-
23. The method of claim 20, wherein the amount of first fluid injected into the capillary channel is less than 100 nl.
-
24. The method of claim 20, wherein the amount of first fluid injected into the capillary channel is less than 10 nl.
-
25. The method of claim 20, wherein the amount of first fluid injected into the capillary channel is less than 1 nl.
-
26. The method of claim 20, wherein the amount of first fluid injected into the capillary channel is between about 0.1 pl and 100 nl.
-
27. The method of claim 20, wherein the capillary channel has a cross sectional area of between about 10 μ
- m2 and 1×
105 m2, and the first selected time is less than 30 seconds.
- m2 and 1×
-
28. The method of claim 27, wherein the first selected time is less than about 10 seconds.
-
29. The method of claim 27, wherein the first selected time is less than about 5 seconds.
-
30. The method of claim 27, wherein the first selected time is less than or equal to about 1 second.
-
31. The method of claim 1, wherein the capillary channel is in fluid communication with at least a first microscale channel disposed in a body structure, and the first fluid is transported through the capillary channel and into the first microscale channel.
-
32. The method of claim 31, wherein the first microscale channel is intersected by and in fluid communication with at least a second microscale channel disposed in the body structure.
-
33. The method of claim 32, further comprising:
-
flowing a component of a biochemical system into the first microscale channel from the second microscale channel whereby the first fluid contacts the component of the biochemical system; and
detecting an effect of the first fluid on the component of the biochemical system.
-
-
34. The method of claim 1, further comprising introducing first and second high salt fluid regions into the capillary channel before and after, respectively, the amount of first fluid injected into the capillary channel.
-
35. The method of claim 34, further comprising introducing first and second low salt fluid regions into the capillary channel before the first high salt fluid region and after the second high salt fluid region, respectively.
-
36. A method of reducing or eliminating spontaneous injection, the method comprising:
-
(i) dipping an open end of an open ended fluid-filled capillary element into a source of a first fluid and applying a negative pressure to the first fluid, thus injecting the first fluid into the capillary element; and
, (ii) changing the negative pressure to a positive pressure or a zero pressure, thereby reducing or eliminating spontaneous injection of the first fluid.- View Dependent Claims (37, 38, 39, 40, 41, 42, 43)
(iii) dipping the open end of the open ended fluid filled capillary element into a source of a second fluid;
(iv) changing the positive pressure or zero pressure to a negative pressure, thereby injecting the second fluid into the capillary element.
-
-
38. The method of claim 36, comprising applying a negative pressure of about −
- 1 to about −
2 psi.
- 1 to about −
-
39. The method of claim 36, comprising changing the negative pressure to a positive pressure of about 1 to about 3 psi.
-
40. The method of claim 39, comprising changing the negative pressure to a positive pressure of about 0.1 to about 0.3 psi.
-
41. The method of claim 36, comprising changing the negative pressure to a pressure substantially equal to the magnitude of the spontaneous injection.
-
42. The method of claim 36, comprising applying a negative pressure in one or more wells and changing the negative pressure in the one or more wells to a positive pressure or a zero pressure concurrent with step (ii).
-
43. The method of claim 42, wherein the wells comprise one or more of:
- a substrate well, an enzyme well, and a waste well.
-
44. A method of screening one or more samples in a microfluidic enzyme inhibition assay, the method comprising:
-
(i) introducing one or more samples into a microfluidic device; and
,(ii) introducing at least one inactivating reagent before the one or more samples, after the one or more samples, or between at least two of the one or more samples. - View Dependent Claims (45, 46, 47, 48, 49)
-
-
50. A microfluidic device, comprising:
-
a glass or quartz body structure having disposed therein an integrated channel structure than includes at least first and second intersecting microscale channels, at least the first channel terminating in a substantially rectangular opening in the body structure;
a capillary element having a capillary channel disposed therethrough, and at least one end of the capillary element that is substantially rectangular, the substantially rectangular end of the capillary element being inserted into the substantially rectangular opening in the body structure and positioned such that the capillary channel in the capillary element is in fluid communication with at least first microscale channel in the body structure. - View Dependent Claims (51, 52, 53, 54, 55, 56, 57)
a first planar substrate having a first surface having a plurality of intersecting grooves fabricated thereon, and at least a first substantially rectangular notch fabricated into the surface along one edge of the substrate, at least one of the plurality of grooves terminating in the first notch;
a second planar substrate comprising a first surface having a second substantially rectangular notch fabricated in the first surface of the second substrate along an edge of the second substrate, the first surface of the second planar substrate overlaying the first surface of the first planar substrate whereby the second notch and the first notch form the substantially rectangular opening in the body structure.
-
-
52. The method of claim 51 wherein the capillary element is substantially coplanar with the first and second planar substrates.
-
53. The microfluidic device of claim 51, wherein the capillary channel in the capillary element comprises a cross-sectional area that is approximately equal to a cross sectional area of the at least first microscale channel in the body structure.
-
54. The microfluidic device of claim 51, wherein the capillary element comprises a curved portion that is not coplanar with the first and second planar substrates.
-
55. The microfluidic device of claim 51, wherein the capillary element comprises a sheath disposed over an outer surface of the capillary element.
-
56. The microfluidic device of claim 51, wherein the sheath is selected from plastic, polyimide and polytetrafluoroethylene.
-
57. The microfluidic device of claim 51, wherein the capillary element is fixedly inserted into the opening.
-
58. A method of joining a capillary element to a microfluidic device having an integrated channel network disposed therein, comprising:
-
providing a glass or quartz microfluidic device having a body structure with at least first and second intersecting microscale channels disposed therein, and having a substantially rectangular opening disposed in the body structure, at least one of the first and second microscale channels terminating in and being in communication with the opening;
providing a substantially rectangular capillary element having first and second ends and a capillary channel disposed through the capillary element from the first end to the second end, and wherein the sec6nd end has a substantially rectangular shape; and
inserting the second end of the capillary element into the opening, the capillary channel in the capillary element being positioned to be in fluid communication with the at least one of the first and second microscale channels that is in communication with the opening.
-
-
59. A method of introducing a fluid material into a microfluidic device, comprising:
-
providing a microfluidic device, comprising;
a glass or quartz body structure having disposed therein an integrated channel network that includes at least first and second intersecting microscale channels, at least the first channel terminating in a substantially rectangular opening in the body structure. a capillary element having first and second ends and a capillary channel disposed therethrough from the first to the second end, the second end of the capillary element being substantially rectangular, the second end of the capillary element being inserted into the substantially rectangular opening in the body structure and positioned such that the capillary channel in the capillary element is in fluid communication with at least first microscale channel in the body structure;
pacing the first end of the capillary element into a source of the fluid material;
drawing an amount of the fluid material into the capillary channel;
transporting the amount of the fluid material through the capillary channel into the at least one of the first and second microscale channels. - View Dependent Claims (60)
-
-
61. A microfluidic device comprising:
-
a glass or quartz body structure having at least first and second channel segments disposed therein, the first and second channel segments each having first and second ends, the first end of the first channel being in fluid communication with the first end of the second channel at a first fluid junction; and
a capillary element attached to and extending from the body structure, the capillary element comprising a capillary channel disposed therethrough, the capillary channel being in fluid communication at one end with the first and second channel segments at the first fluid junction. - View Dependent Claims (62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77)
a first substrate having at least a first planar surface, the first planar surface having first and second groove segments disposed thereon;
a second substrate having a first planar surface, the first planar surface of the second substrate being mated with the first planar surface of the first substrate, the first and second groove segments defining the first and second channel segments.
-
-
74. The microfluidic device of claim 73, wherein the capillary element is attached to the body structure and the capillary channel is in fluid communication with the first fluid junction via an opening disposed through the body structure.
-
75. The microfluidic device of claim 74, wherein the opening disposed through the body structure comprises an opening disposed through at least one of the first and second substrates, the capillary element being fixedly inserted into the opening.
-
76. The microfluidic device of claim 74, wherein the opening in the body structure comprises a third groove segment disposed in the first surface of the first substrate and having first and second ends, the first end of the third groove segment terminating at one end at a first edge of the first planar surface of the first substrate and defining a third channel segment having first and second ends in the body structure, the first end of the third channel segment defining an opening in a first edge of the body structure, and the second end of the third channel segment being in fluid communication with the first fluid junction.
-
77. The microfluidic device of claim 76, wherein the capillary element is attached to the body structure at the first edge of the body structure and wherein the capillary channel is in fluid communication with the third channel segment.
-
78. A method of transporting material in a microscale channel, comprising:
-
introducing a first fluid into the channel, having a first electroosmotic mobility, and a first conductivity;
introducing a second fluid into the channel, having a second electroosmotic mobility and a second conductivity different from the first conductivity; and
varying a voltage gradient applied across a length of the channel to maintain a substantially constant average electroosmotic flow rate, despite a change in a total resistance of the channel. - View Dependent Claims (79, 80, 81, 82, 83, 84, 85, 86, 87)
-
-
88. A microfluidic system. comprising:
-
a microfluidic device comprising a microscale channel disposed therein, the microscale channel containing varying volumes of first and second fluids over time, the first and second fluids having first and second conductives, respectively;
an electrical controller operably coupled to the microscale channel for applying a variable electric field across a length of the microscale channel;
a computer operably coupled to the electrical controller, and appropriately programmed to instruct the controller to vary the electric field to maintain a constant average electroosmotic flow rate within the channel, despite a change in total resistance across the length of the channel resulting from the varying volumes of first and second fluids over time. - View Dependent Claims (89, 90, 91, 92, 93, 94, 95, 96)
-
Specification