Method for manufacturing a microfluidic sensor

• US 8,182,635 B2
• Filed: 04/07/2009
• Issued: 05/22/2012
• Est. Priority Date: 04/07/2008
• Status: Active Grant

• Current Assignee: Orflo Technologies, LLC
• Original Assignee: E.I Spectra, LLC dba ORFLO Technologies (Gemini Bioproducts LLC)
• Inventors: Ayliffe, Harold E., King, Curtis S.
• Primary Examiner(s): Tucker, Philip
• Assistant Examiner(s): Chan, Sing P
• Application Number:
  US12/936,243
• Publication Number:
  US 20110030888A1
• Time in Patent Office: 1,141 Days
• Field of Search: 156/277, 156/278, 156/250, 156/252, 156/256, 324/434, 324/425, 324/439, 324/71.1, 324/692, 324/722, 204/400, 204/402, 204/406, 204/415, 205/778, 205/781.5, 422/44, 422/56, 422/61, 422/67, 422/82.01, 422/82.02, 436/16, 436/63, 436/66, 436/68, 436/178
• US Class Current: 156/252
• CPC Class Codes: B01L 2200/0647 Handling flowable solids, e.g. microscopic beads, cells, particles
• CPC Class Codes: B01L 2200/10 Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
• CPC Class Codes: B01L 2300/0645 Electrodes
• CPC Class Codes: B01L 2300/0681 Filter
• CPC Class Codes: B01L 2300/0874 Three dimensional network
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2300/123 Flexible; Elastomeric
• 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: Y10T 156/1056 Perforating lamina
• CPC Class Codes: Y10T 156/1062 Prior to assembly
• CPC Class Codes: Y10T 29/49117 Conductor or circuit manufacturing
• CPC Class Codes: Y10T 29/49155 Manufacturing circuit on or in base

Abstract

A method to manufacture microfluidic sensors, typically including componentizing substrate layers One such method includes providing a plurality of layers of material configured to permit their stacking to form at least a first cap layer, a first channel layer, an interrogation layer, and a second channel layer During assembly, ribbon sections of substrate layers are sandwiched to cooperatively align elements through-the-thickness of the sandwich Individual sensors are then removed from the sandwich ribbon A componentizing step includes forming one or more elements for successive sensors spaced along the axial length of a ribbon Certain elements include electrically conductive patterned structures preferably printed onto a substrate using conductive ink and a printing process, sometimes placing material in operable position to conduct electricity through the thickness of at least one nbbon Other elements may include channels, tunnels, and vias that can be machined, stamped, or cut into a ribbon section.

Claims

1. A method for manufacturing a microfluidic sensor, comprising:

providing a thin film substrate configured as an electrically insulating barrier effective to resist fluid and particle travel through uninterrupted portions there-of;

applying electrically conductive ink, by way of a printing process, onto both sides of said substrate to form at least one electrode disposed on each side of said substrate;

forming a first tunnel through said thin film substrate by removing material from a portion of said thin film substrate to permit fluid passage there-through, said first tunnel being sized less than about 0.2 mm in a cross-section length to promote passage there-through of particles of interest in substantially single-file travel; and

providing channel structure configured such that all fluid flowing from a position of contact with a first electrode disposed on a first side of said thin film substrate must pass through said first tunnel before encountering a second electrode disposed on the opposite side of said thin film substrate.

2. The method according to claim 1, further comprising:

forming circuit-forming contacts, as electrically communicating extensions of individual ones of said electrodes, on a single side of said substrate, at least one circuit-forming contact being disposed in electrical communication with an electrode, carried on the opposite side of said substrate, by way of an electrically communicating via.

3. The method according to claim 1, wherein the step of providing channel structure comprises:

adhering a first channel layer in registration with one side of said substrate to dispose a first channel element associated with said first channel layer for fluid communication through said tunnel;

adhering a second channel layer in registration with the other side of said substrate to dispose a second channel element associated with said second channel layer for fluid communication through said tunnel and with said first channel element; and

disposing a first electrode carried by said substrate to contact fluid flowing in said first channel element; and

disposing a second electrode carried by said substrate to contact fluid flowing in said second channel element.

4. The method according to claim 3, further comprising:

disposing a third electrode for contact with fluid flowing between said first electrode and said second electrode; and

configuring said first electrode and said second electrode in harmony with a respective local portion of respective associated channel elements effective to dispose a surface area, sized in excess of about 5 mm², of each such electrode for contact with fluid flowing through said channel portion.

5. The method according to claim 4, further comprising:

disposing a fourth electrode for contact with fluid flowing between said first electrode and said second electrode.

6. The method according to claim 3, further comprising:

configuring electrodes, during said printing process, in a pattern disposed to cooperate with a portion of one or more channel element effective to permit electrically-based interrogation of a known volume of fluid with said sensor.

7. The method according to claim 3, further comprising:

configuring electrodes, during said printing process, in a pattern effective to permit detection of a signal indicating arrival of a fluid wave-front at a known position in said sensor.

8. The method according to claim 3, further comprising:

configuring electrodes, during said printing process, in a pattern effective to permit particle detection in an interrogation zone comprising said tunnel.

9. The method according to claim 3, further comprising:

disposing a third electrode for contact with fluid flowing between said first electrode and said second electrode; and

disposing said third electrode upstream of said tunnel such that fluid flows completely along the length of said third electrode before flowing into said tunnel.

10. The method according to claim 3, further comprising:

disposing a third electrode for contact with fluid flowing between said first electrode and said second electrode; and

disposing said third electrode downstream of said tunnel such that fluid flows completely along the length of said third electrode before contacting said second electrode.

11. The method according to claim 1, further comprising:

forming circuit-forming contacts, as electrically communicating extensions of individual ones of said electrodes, on both sides of said substrate.

12. A method for manufacturing a multilayer microfluidic sensor, comprising:

providing a plurality of layers of material configured to permit their stacking to form at least a first cap layer, a first channel layer, an interrogation layer, and a second channel layer, said interrogation layer comprising a thin film substrate configured as an electrically insulating barrier effective to resist fluid and particle travel through uninterrupted portions there-of;

printing electrically conductive ink onto said interrogation layer to form electrodes that are disposed spaced apart along, and on both sides of, said interrogation layer;

stacking and cooperatively adhering said layers to form an integrated multilayer sandwich, wherein;

said first channel layer carries a plurality of first channel elements disposed spaced apart along a length axis of said first channel layer;

said interrogation layer carries a plurality of tunnel elements that are formed by removing material from said interrogation layer and that are sized to promote travel there-through of particles of interest in substantially single-file and are disposed spaced apart along a length axis of said interrogation layer; and

said second channel layer carries a plurality of second channel elements disposed spaced apart along a length axis of said second channel layer;

further comprising;

separating a plurality of sensors from said sandwich such that each separated sensor includes a lumen adapted to permit fluid flow there-through, said lumen comprising a first channel element disposed in fluid communication, through a tunnel element, with a second channel element, said lumen being arranged such that fluid and particle flow from said first channel element to said second channel element must pass through said tunnel element.

13. The method according to claim 12, wherein:

said first channel layer and said second channel layer are formed from double-sided self-adhesive film.

14. The method according to claim 12, wherein:

said stacking and adhering includes use of indexing structure effective to operably align elements of individual sensors through-the-thickness of said sandwich.

15. The method according to claim 12, further comprising:

using a printing process to apply said electrodes onto said interrogation layer in a pattern effective to dispose a plurality of electrodes spaced apart along a length axis of said interrogation layer such that at least one electrode is included in each separated sensor, said at least one electrode being disposed to contact fluid flowing through said lumen.

16. The method according to claim 15, further comprising:

applying said electrodes to said interrogation layer in a pattern that is repeated along a length direction of said interrogation layer.

17. The method according to claim 15, further comprising:

applying said electrodes to both sides of said interrogation layer, and applying surface contact electrodes on only one side of said interrogation layer, at least one surface contact electrode being in electrical communication with an electrode carried on the other side of said interrogation layer by way of an electrically conductive via.

18. The method according to claim 12, further comprising:

forming said plurality of tunnel elements subsequent to printing said electrodes on said interrogation layer.

19. The method according to claim 12, further comprising:

pre-forming elements associated with certain layers in a reel-to-reel operation effective to form one or more componentized layer, and;

stacking said one or more componentized layer in a reel-to-reel process to form said sandwich.

20. The method according to claim 12, further comprising:

pre-forming elements associated with certain layers in a reel-to-reel operation effective to form one or more componentized layer, and;

stacking discrete lengths of said one or more componentized layer to form said sandwich.

21. The method according to claim 20, further comprising:

applying a discrete substrate to said second channel layer.