Microfluidic array devices and methods of manufacture and uses thereof

• US 6,800,849 B2
• Filed: 06/17/2002
• Issued: 10/05/2004
• Est. Priority Date: 12/19/2001
• Status: Expired due to Fees

• Current Assignee: Phoenix S&T, Inc.
• Original Assignee: Sau Lan Tang Staats
• Inventors: Staats, Sau Lan Tang
• Primary Examiner(s): Lee, John R.
• Assistant Examiner(s): Gill, Erin-Michael
• Application Number:
  US10/174,343
• Publication Number:
  US 20030111599A1
• Time in Patent Office: 841 Days
• Field of Search: 250/423.R, 250/424, 250/428, 250/432.R, 250/435, 250/288, 239/424.5
• US Class Current: 250/288
• CPC Class Codes: B01J 2219/0036 Nozzles
• CPC Class Codes: B01L 2200/021 Adjust spacings in an array of wells, pipettes or holders, format transfer between arrays of different size or geometry
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• CPC Class Codes: B01L 2400/027 electrostatic forces between substrate and tip
• CPC Class Codes: B01L 2400/0481 squeezing of channels or chambers
• CPC Class Codes: B01L 3/0241 Drop counters; Drop formers making arrays for combinatorial libraries B01J19/0046; automation of dispensing for analysis G01N35/10
• CPC Class Codes: B01L 3/0268 using pulse dispensing or spraying, eg. inkjet type, piezo actuated ejection of droplets from capillaries
• CPC Class Codes: B01L 3/5025 for parallel transport of multiple samples
• CPC Class Codes: B01L 3/5027 by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• CPC Class Codes: B01L 3/502707 characterised by the manufacture of the container or its components by shaping or joining plastic parts B29C59/00, B29C65/00; by laminating B32B37/00; manufacture of microstructural devices in general B81C
• CPC Class Codes: B01L 9/527 for microfluidic devices, e.g. used for lab-on-a-chip
• CPC Class Codes: B33Y 80/00 Products made by additive manufacturing
• CPC Class Codes: C40B 60/14 for creating libraries
• CPC Class Codes: G01N 2030/285 electrically driven carrier
• CPC Class Codes: G01N 2035/1039 Micropipettes, e.g. microcapillary tubes
• CPC Class Codes: G01N 27/44782 of a plurality of samples
• CPC Class Codes: G01N 27/44791 Microapparatus sample containers with integrated microfluidic structures B01L3/5027
• CPC Class Codes: G01N 30/6026 Fluid seals
• CPC Class Codes: G01N 30/6095 Micromachined or nanomachined, e.g. micro- or nanosize
• CPC Class Codes: G01N 35/1074 arranged in a two-dimensional array
• CPC Class Codes: H01J 49/0431 : for liquid samples interfaces to liquid chromatographs G01N30/7233

Abstract

Microfluidic nozzle array devices are provided with the body of each device having at least one nozzle extending outwardly from one surface of the body. Each nozzle includes a tip opening having a diameter of equal to or less than about 100 μm, preferably 50 μm, and more preferably 20 μm and an outer diameter of nozzle is equal to or less than about 150 μm, preferably 100 μm, and more preferably 50 μm. The microfluidic nozzle array devices are fabricated using an injection molding process and find particular utility in a wide range of applications, including but not limited to nanospray/electrospray applications, mass spectrometer applications, optical spectrometry applications, spotting applications (i.e., DNA or protein array), etc.

Claims

1. A microfluidic device comprising:

an injection molded article including;

a body having a first surface and an opposing second surface, the body having at least one channel formed therein and extending through the body from the first surface to the second surface, wherein the channel has a reservoir section that is open at the first surface; and

at least one nozzle disposed along the second surface, the nozzle being in fluid communication with the channel such that one end of the channel terminates in a nozzle opening that is formed as part of the nozzle, wherein the device is formed of an injection moldable material.

2. The microfluidic device of claim 1, wherein the channel has a cylindrical shape along at least a substantial length thereof, the channel being defined by a seamless cylindrical surface.

3. The microfluidic device of claim 1, wherein the channel is inwardly tapered such that the dimensions of the channel are greatest in the reservoir section and are at a minimum at the nozzle opening.

4. The microfluidic device of claim 1, wherein the channel is formed in the reservoir section so that it is substantially perpendicular to both the first and second surfaces.

5. The microfluidic device of claim 1, wherein the at least one nozzle extends beyond the second surface and is substantially conically shaped.

6. The microfluidic device of claim 5, wherein the nozzle has an outside diameter equal to or less than about 50 μ

m.

7. The microfluidic device of claim 1, wherein the nozzle has an outside diameter equal to or less than about 100 μ

m.

8. The microfluidic device of claim 1, wherein the nozzle opening has a diameter equal to or less than about 20 μ

m.

9. The microfluidic device of claim 1, wherein the nozzle opening has a diameter equal to or less than about 50 μ

m.

10. The microfluidic device of claim 1, wherein a portion of the channel that is formed in the nozzle and that terminates in the nozzle opening is inwardly tapered toward the nozzle opening.

11. The microfluidic device of claim 1, wherein the at least one channel and the at least one nozzle are arranged in a geometrical array.

12. A The microfluidic device of claim 1, further including:

a conductive region formed on the second surface around a periphery of the at least one nozzle.

13. The microfluidic device of claim 12, wherein the conductive region is formed of metal and is electrically connected to an electric contact.

14. The microfluidic device of claim 13, wherein the electrical contact is formed on the second surface along a single edge of the body.

15. The microfluidic device of claim 1, wherein the channel has a first section in which inner channel surfaces are parallel, the first section at least partially defining the reservoir section and extending to the first surface, the channel further including a second section in which the inner channel surfaces are in a non-parallel relationship, the second section extending from the first section to the nozzle opening.

16. A microfluidic device comprising:

an injection molded microfluidic device formed of an injection moldable material comprising;

a body having a first surface and an opposing second surface, the body having at least one channel formed therein, the channel extending through the body from the first surface to the second surface, wherein the channel has a reservoir section that is open at the first surface for receiving a sample; and

at least one nozzle integrally formed with the body and disposed along and extending beyond the second surface, the nozzle being defined by outer surfaces that are non-parallel in nature and the number of nozzles being equal to the number of channels with each nozzle having a section of the channel formed therethrough such that each channel terminates in a nozzle opening of the nozzle, wherein a diameter of the nozzle opening is equal to or less than about 100 μ

m and an outside diameter of the nozzle is equal to or less than about 150 μ

m and wherein the channel section formed in the nozzle is defined by non-parallel surfaces that terminate at one end with the formation of the nozzle opening.

17. The microfluidic device of claim 16, wherein a diameter of the nozzle opening is equal to or less than about 150 μ

m and an outside diameter of the nozzle is equal to or less than about 100 μ

m.

18. The microfluidic device of claim 16, wherein a diameter of the nozzle opening is equal to or less than about 20 μ

m and an outside diameter of the nozzle is equal to or less than about 50 μ

m.

19. The microfluidic device of claim 16, further including:

a device for sealing the reservoir section and for transporting the sample from the reservoir section through the channel to the nozzle opening where the sample is discharged.

20. The microfluidic device of claim 16, further including:

a seal in the form of a deformable, elastic polymeric cover sheet that is initially disposed across an open end of the reservoir section such that it is attached to and across the first surface and a shaft for engaging the polymeric cover sheet, wherein when the shaft is driven to an extended position, the polymeric cover sheet is deformed and forms a seal with an inner surface of the reservoir section and forces the sample to flow toward the nozzle opening where it is discharged.

21. The microfluidic device of claim 19, wherein the transport device comprises a displaceable member including a base with a deformable seal extending therearound, the base being initially disposed across an open end of the reservoir section with a shaft being connected to the base, wherein when the shaft is driven to an extended position, the base is received within the reservoir section and the flange forms a seal with an inner surface of the reservoir section and forces the sample to flow toward the nozzle opening where it is discharged.

22. The microfluidic device of claim 19, wherein the transport device comprises a member having a bore formed therethrough with a gasket being disposed at a distal end of the member, the gasket forming a seal between the member and the reservoir section, wherein the member is in communication with a source of fluid that is introduced into the reservoir section to force the sample to flow toward the nozzle opening where it is discharged.

23. The microfluidic device of claim 22, wherein the fluid comprises a gas.

24. The microfluidic device of claim 22, wherein the fluid comprises the sample.

25. The microfluidic device of claim 22, wherein the gasket comprises an O-ring that is disposed between the distal end and the first surface of the body, the O-ring being free of interference with the fluid flowing through the bore into the reservoir section.

26. The microfluidic device of claim 16, wherein the body and the at least one nozzle comprise a single injection-molded structure that is formed of a polymeric material.

27. The microfluidic device of claim 16, wherein the at least one nozzle comprises an array of nozzles arranged according to a predetermined pattern along the second surface of the body.

28. The microfluidic device of claim 27, wherein the nozzle array includes a predetermined number of nozzles arranged in axial rows across the second surface.

29. A detection system for detecting one or more properties of a sample, the detection system including:

an injection molded microfluidic device formed of an injection moldable material comprising;

a body having a first surface and an opposing second surface, the body having at least one channel formed therein, the channel extending through the body from the first surface to the second surface, wherein the channel has a reservoir section that is open at the first surface; and

at least one nozzle integrally formed with the body and disposed along and extending beyond the second surface, the nozzle defined by outer surfaces that are non-parallel in nature and the number of nozzles equal to the number of channels with each nozzle having a section of the channel formed therethrough such that each channel terminates in a nozzle opening that is formed as part of the nozzle, wherein a diameter of the nozzle opening is equal to or less than about 100 μ

m and an outside diameter of the nozzle is equal to or less than about 150 μ

m and wherein the channel section formed in the nozzle is defined by tapered inner surfaces that terminate at one end with the formation of the nozzle opening; and

a detector for receiving the sample discharged from the microfluidic device through the nozzle opening thereof, wherein the detector analyzes the discharged sample and provides information regarding one or more properties of the sample.

30. The detection system of claim 29, wherein the detector is a mass spectrometer.

31. The detection system of claim 29, wherein the diameter of the nozzle opening is equal to or less than 20 μ

m and the outside diameter of the nozzle is equal to or less than 50 μ

m.

32. The detection system of claim 29, wherein the body includes a thin conductive film disposed on the second surface around each nozzle, the conductive film being connected to a source of electricity so that when an electric field is applied to the conductive film, the sample is vaporized and ionized as it is discharged through the nozzle opening.

33. A The detection system of claim 29, wherein the sample is formed of a liquid and analytes.

34. The detection system of claim 33, wherein the detector is a mass spectrometer and the liquid comprises a water and at least one component selected from the group consisting of acetonitrile, methanol, and ammonium acetate.

35. The detection system of claim 29, further including:

a device for sealing the reservoir section and for transporting the sample from the reservoir section through the channel to the nozzle opening where the sample is discharged.

36. The detection system of claim 35, wherein the transport device comprises a displaceable member including a deformable, elastic polymeric cover sheet that is initially disposed across an open end of the reservoir section and a shaft that is connected to the polymeric cover sheet, wherein when the shaft is driven to an extended position, the polymeric cover sheet forms a seal with an inner surface of the reservoir section and forces the sample to flow toward the nozzle opening where it is discharged.

37. The detection system of claim 35, wherein the transport device comprises a displaceable member including a base with a deformable seal extending therearound, the base being initially disposed across an open end of the reservoir section with a shaft being connected to the base, wherein when the shaft is driven to an extended position, the base is received within the reservoir section and the flange forms a seal with an inner surface of the reservoir section and forces the sample to flow toward the nozzle opening where it is discharged.

38. The detection system of claim 35, wherein the transport device comprises a member having a bore formed therethrough with a gasket being disposed at a distal end of the member, the gasket forming a seal between the member and the reservoir section, wherein the member is in communication with a source of fluid that is introduced into the reservoir section under predetermined conditions to force the sample to flow toward the nozzle opening where it is discharged.

39. The detection system of claim 38, wherein the fluid comprises a gas.

40. A process for creating a vaporized and ionized fluid stream from a liquid sample for injection into a diagnostic device, the process comprising the steps of:

providing an injection molded microfluidic device formed of an injection moldable material comprising;

a body having a first surface and an opposing second surface, the body having at least one channel formed therein, the channel extending through the body from the first surface to the second surface, wherein the channel has a reservoir section that is open at the first surface; and

at least one nozzle integrally formed with the body and disposed along and extending beyond the second surface, the number of nozzles equal to the number of channels with each nozzle being in fluid communication with one channel such that each channel terminates in a nozzle opening that is formed as part of the nozzle, wherein a diameter of the nozzle opening is equal to or less than about 50 μ

m and an outside diameter of the nozzle is equal to or less than about 100 μ

m;

disposing a sample in the channel at least within the reservoir section;

transporting the sample from the reservoir to the nozzle tip where the sample is discharged; and

applying an electric field to the second surface of the body around each nozzle, the electric field being of sufficient strength so as to cause the discharged sample to be vaporized and ionized.

41. The process of claim 40, wherein the diameter of the nozzle opening is equal to or less than 50 μ

m and the outside diameter of the nozzle is equal to or less than about 100 μ

m.

42. The process of claim 40, wherein the step of transporting the sample comprises:

providing a transportation mechanism at the first surface adjacent the open reservoir section; and

manipulating the transportation mechanism to cause a force to be applied to the sample in the direction toward the nozzle opening such that the sample flows to and is discharged through the nozzle opening.

43. The process of claim 42, wherein the transportation mechanism includes a displaceable member having a deformable, elastic polymeric cover sheet and a shaft coupled to the polymeric cover sheet and wherein the step of manipulating the mechanism includes the step of driving the shaft from a retracted position to an extended position, the polymeric cover sheet forming a seal with an inner surface of the reservoir section and wherein the polymeric cover sheet forces the sample to flow to and be discharged through the nozzle opening as the shaft is driven to the extended position.

44. The process of claim 42, wherein the transportation mechanism includes a displaceable member having a base with a sealing flange extending therearound and a shaft coupled to the base and wherein the step of manipulating the mechanism includes the step of driving the shaft from a retracted position to an extended position, the flange forming a seal with an inner surface of the reservoir section and wherein the base forces the sample to flow to and be discharged through the nozzle opening as the shaft is driven to the extended position.

45. The process of claim 42, wherein the transportation mechanism includes a member having a bore formed therethrough with a gasket providing a seal between the member and the first surface of the body, the bore being in communication with a fluid source at one end and with the reservoir section at the other end and wherein the step of manipulating the mechanism includes causing the fluid to flow through the bore and into reservoir section where it applies a force to the sample, resulting in the sample being discharged from the nozzle opening.

46. A process for array spotting on a substrate, the process comprising the steps of:

providing a microfluidic device comprising;

an injection molded microfluidic device formed of an injection moldable material comprising;

a body having a first surface and an opposing second surface, the body having at least one channel formed therein, the channel extending through the body from the first surface to the second surface, wherein the channel has a reservoir section that is open at the first surface for receiving a sample; and

a plurality of nozzles integrally formed with the body and disposed along and extending beyond the second surface, each nozzle defined by outer surfaces that are non-parallel in nature and the number of nozzles equal to the number of channels with each nozzle having a section of the channel formed therethrough such that each channel terminates in a nozzle opening that is formed as part of the nozzle, wherein a diameter of the nozzle opening is equal to or less than about 100 μ

m and an outside diameter of the nozzle is equal to or less than about 150 μ

m and wherein the channel section formed in the nozzle is defined by tapered inner surfaces that terminate at one end with the formation of the nozzle opening;

disposing one or more samples within the plurality of reservoir sections, with only one sample being disposed in one reservoir section;

positioning the microfluidic device proximate to the substrate with the plurality of nozzles facing the substrate; and

transporting each sample from one reservoir to a respective nozzle tip where the sample is discharged through the nozzle opening onto the substrate to form a sample spot on the substrate.

47. The process of claim 46, wherein the diameter of the nozzle opening is equal to or less than about 20 μ

m and the outside diameter of the nozzle is equal to or less than about 50 μ

m.

48. The process of claim 46, wherein the samples contain DNA segments so that the resulting array of spots is a DNA array spotting.

49. The process of claim 46, wherein the samples contain protein molecules so that the resulting array of spots is a protein array spotting.

50. The process of claim 46, further including the step of:

pumping the sample through channel to the nozzle opening with high pressure air that is directed into the reservoir section.

51. The process of claim 46, further including the step of:

applying an electric field to the second surface of the body around each nozzle, the electric field being of sufficient strength so as to cause the discharged sample to be vaporized and ionized.

52. A microfluidic device comprising:

an injection molded article including;

a body having a first surface and an opposing second surface, the body having at least one channel formed therein and extending through the body from the first surface to the second surface, wherein the channel has a reservoir section that is open at the first surface; and

at least one nozzle disposed along the second surface and having a length of the channel formed therethrough such that one end of the channel terminates in a nozzle opening that is formed as a distal end of the nozzle, wherein the device is formed of an injection moldable material and the length of channel formed in the nozzle has a varying diameter.

53. The microfluidic device of claim 52, wherein the nozzle is defined by tapered outer surfaces that terminate at one end with the nozzle opening.

54. The microfluidic device of claim 52, wherein the diameter of the channel formed in the nozzle is at a minimum at the nozzle opening.

55. The microfluidic device of claim 52, wherein the nozzle has a continuously varying diameter.

56. The microfluidic device of claim 52, wherein wall that defines the length of channel formed in the nozzle extends linearly along its length.