Compact fluid analysis device and method to fabricate

• US 9,617,149 B2
• Filed: 12/11/2014
• Issued: 04/11/2017
• Est. Priority Date: 05/22/2013
• Status: Active Grant

• Current Assignee: IMEC International
• Original Assignee: IMEC International
• Inventors: Lagae, Liesbet, Peumans, Peter
• Primary Examiner(s): BOWERS, NATHAN ANDREW
• Application Number:
  US14/567,301
• Publication Number:
  US 20150093816A1
• Time in Patent Office: 852 Days
• CPC Class Codes: A61B 5/1411 by percutaneous method, e.g. by lancet
• CPC Class Codes: A61B 5/150022 for capillary blood or interstitial fluid
• CPC Class Codes: A61B 5/150221 Valves
• CPC Class Codes: A61B 5/150274 Manufacture or production processes or steps for blood sampling devices
• CPC Class Codes: A61B 5/150358 Strips for collecting blood, e.g. absorbent optical reagent test strips G01N21/8483; chemical reagent test strips G01N33/4875, G01N33/52
• CPC Class Codes: A61B 5/15087 short range, e.g. between console and disposable using implanted devices A61B5/150877
• CPC Class Codes: B01L 2300/046 Function or devices integrated in the closure
• CPC Class Codes: B01L 2300/0645 Electrodes
• CPC Class Codes: B01L 2300/0663 Whole sensors
• CPC Class Codes: B01L 2300/0681 Filter
• CPC Class Codes: B01L 2300/0819 Microarrays; Biochips
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2300/123 Flexible; Elastomeric
• CPC Class Codes: B01L 2300/1833 using electrical currents in the sample itself
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/0415 electrical forces, e.g. electrokinetic
• CPC Class Codes: B01L 2400/0688 surface tension valves, capillary stop, capillary break
• CPC Class Codes: B01L 2400/086 using baffles or other fixed flow obstructions
• 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 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/50273 : characterised by the means or forces applied to move the fluids micropumps F04B19/006, of the membrane type F04B43/043
• CPC Class Codes: B01L 7/52 : with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples amplification or hybridisation processes per se C12Q1/68; controlling sequential reactions for synthesis B01J19/0046
• CPC Class Codes: B81C 1/00238 : Joining a substrate with an electronic processing unit and a substrate with a micromechanical structure
• CPC Class Codes: B81C 1/00539 : Wet etching
• CPC Class Codes: F15C 5/00 : Manufacture of fluid circuit elements; Manufacture of assemblages of such elements integrated circuits
• CPC Class Codes: F15C 7/00 : Hybrid elements, i.e. circuit elements having features according to groups F15C1/00 and F15C3/00
• CPC Class Codes: G01N 27/227 : Sensors changing capacitance upon adsorption or absorption of fluid components, e.g. electrolyte-insulator-semiconductor sensors, MOS capacitors G01N27/225 takes precedence
• CPC Class Codes: G01N 27/4148 : Integrated circuits therefor, e.g. fabricated by CMOS processing CMOS processing per se H01L21/82
• CPC Class Codes: Y10T 29/494 : Fluidic or fluid actuated device making
• CPC Class Codes: Y10T 436/143333 : Saccharide [e.g., DNA, etc.]

Abstract

The present disclosure relates to a device for analyzing a fluid sample. In one aspect, the device includes a fluidic substrate that comprises a micro-fluidic component embedded in the fluidic substrate configured to propagate a fluid sample via capillary force through the device and a means for providing a fluid sample connected to the micro-fluidic component. The device also includes a lid attached to the fluidic substrate at least partly covering the fluidic substrate and at least partly closing the micro-fluidic component. The fluidic substrate may be a silicon fluidic substrate and the lid may be a CMOS chip. In another aspect, embodiments of the present disclosure relate to a method for fabricating such a device, and the method may include providing a fluidic substrate, providing a lid, and attaching, through a CMOS compatible bonding process, the fluidic substrate to the lid to close the fluidic substrate at least partly.

Claims

1. A device for analyzing a fluid sample, the device comprising:

a fluidic substrate comprising;

a micro-fluidic component embedded in the fluidic substrate and configured to propagate a fluid sample via capillary force through the micro-fluidic component, and

a means for providing a fluid sample connected to the micro-fluidic component; and

a lid attached to the fluidic substrate, at least partly covering the fluidic substrate, and at least partly closing the micro-fluidic component,

wherein the fluidic substrate is a silicon fluidic substrate,

and wherein the lid is a Complimentary Metal-Oxide Semiconductor (CMOS) chip, wherein the CMOS chip includes at least one electrical component, and wherein the at least one electrical component is in direct contact with the fluid sample when the fluid sample is present in the device.

2. The device according to claim 1, wherein the lid comprises a transistor layer electrically connected to the at least one electrical component, and wherein the at least one electrical component includes at least one of the following biosensing circuitry, an electrode for sensing purposes, an electrode for fluid manipulation purposes, circuitry for data communication purposes, circuitry for wireless data communication purposes, a temperature sensor, a heater electrode for temperature control, or a fluid sensor and an electrode for fluidic viscosity control.

3. The device according to claim 1, wherein the means for providing a fluid sample is an integrated needle fabricated from silicon and comprising an inner fluidic channel connected to the micro-fluidic component, and wherein the needle is a protruding portion of the fluidic substrate and is positioned to penetrate skin tissue when pressed against the skin tissue.

4. The device according to claim 3, wherein the fluidic substrate comprises a cut-out, and wherein the needle is positioned in the cut-out.

5. The device according to claim 3, wherein the fluidic substrate comprises a protection structure for protecting the needle, and wherein the protection structure is removably attached to the fluidic substrate.

6. The device according to claim 1, wherein the fluidic substrate further comprises at least one optical waveguide to allow optical excitation and sensing of the fluid sample when present in the device.

7. The device according to claim 1, wherein at least one of the fluidic substrate or the lid comprises at least one through-hole for application of a biochemical reagent to at least one region of the micro-fluidic component or to at least one region of the lid.

8. The device according to claim 1, wherein the lid is bonded to the fluidic substrate using a lithographically patterned polymer.

9. The device according to claim 1, further comprising metal contacts electrically connected to the lid for read-out of electrical signals from the lid.

10. The device according to claim 1, wherein at least part of one or more of the fluidic substrate or the lid is fabricated from a transparent material to allow optical inspection of a fluid sample when the fluid sample is present in the micro-fluidic component.

11. The device according to claim 1, wherein the device is configured to allow insertion into a mobile communication device.

12. The device according to claim 1, wherein the micro-fluidic component further includes micro-pillars arranged to create the capillary force that propagates the fluid sample through the micro-fluidic component.

13. The device according to claim 12, wherein the micro-pillars are arranged to create the capillary force by varying one or more of distances between micro-pillars, dimensions of the micro-pillars, or shapes of the micro-pillars.

18. Use of the device according to claim 1 to perform microscopy.

14. A device for analyzing a fluid sample, the device comprising:

a fluidic substrate comprising a micro-fluidic component embedded in the fluidic substrate and configured to propagate a fluid sample via capillary force through the micro-fluidic component, wherein the fluidic substrate is a silicon fluidic substrate; and

a CMOS chip attached to the silicon fluidic substrate, at least partly covering the fluidic substrate, and at least partly closing the micro-fluidic component, wherein the CMOS chip includes at least one electrical component, and wherein the at least one electrical component is in direct contact with the fluid sample when the fluid sample is present in the device.

15. A method for fabricating a device for analyzing a fluid sample, the method comprising:

providing a fluidic substrate comprising a micro-fluidic component embedded in the fluidic substrate and configured to propagate a fluid sample via capillary force through the micro-fluidic component, and a means for providing a fluid sample connected to the micro-fluidic component;

providing a lid; and

attaching the fluidic substrate to the lid to close the fluidic substrate at least partly,

wherein the fluidic substrate is a silicon fluidic substrate and the lid is CMOS chip,

wherein the CMOS chip includes at least one electrical component, and wherein the at least one electrical component is in direct contact with the fluid sample when the fluid sample is present in the device,

and wherein the fluidic substrate is attached to the lid using a CMOS compatible bonding process.

16. The method according to claim 15, wherein providing the fluidic substrate comprises:

providing a silicon substrate, providing an oxide mask, and patterning the oxide mask to create fine structures in the oxide mask;

providing a protection layer to protect the oxide mask;

patterning coarse structures;

etching of the coarse structures;

growing oxide for protecting the coarse structures;

removing the protection layer;

etching the fine structures; and

removing the oxide.

17. The method according to claim 15, wherein surfaces of the fluidic substrate and the lid are partially or fully coated to modify surface interactions of the substrate with the fluid sample.