Microfluidic chips and assay systems

• US 20070166200A1
• Filed: 01/05/2007
• Published: 07/19/2007
• Est. Priority Date: 01/19/2006
• Status: Active Grant

• Current Assignee: Rheonix, Inc.
• Original Assignee: Kionix Incorporated (ROHM Co., Ltd.)
• Inventors: Zhou, Peng, Young, Lincoln
• Granted Patent: US 7,959,875 B2
• Time in Patent Office: Days
• US Class Current: 422/100
• CPC Class Codes: B01L 2200/026 Fluid interfacing between devices or objects, e.g. connectors, inlet details
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• CPC Class Codes: B01L 2200/028 Modular arrangements
• CPC Class Codes: B01L 2200/04 Exchange or ejection of cartridges, containers or reservoirs
• CPC Class Codes: B01L 2200/0621 Control of the sequence of chambers filled or emptied
• CPC Class Codes: B01L 2200/0684 Venting, avoiding backpressure, avoid gas bubbles
• 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 2200/16 Reagents, handling or storing thereof
• CPC Class Codes: B01L 2300/0654 Lenses; Optical fibres
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0864 comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2300/0874 Three dimensional network
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2300/1827 using resistive heater
• CPC Class Codes: B01L 2400/0481 squeezing of channels or chambers
• CPC Class Codes: B01L 2400/0622 distribution valves, valves having multiple inlets and/or outlets, e.g. metering valves, multi-way valves
• CPC Class Codes: B01L 2400/0633 with moving parts
• CPC Class Codes: B01L 2400/0655 pinch valves
• CPC Class Codes: B01L 2400/0666 Solenoid valves
• CPC Class Codes: B01L 2400/084 : Passive control of flow resistance
• CPC Class Codes: B01L 3/5025 : for parallel transport of multiple samples
• 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 3/502738 : characterised by integrated valves microvalves F16K99/0001
• CPC Class Codes: B01L 7/00 : Heating or cooling apparatus autoclaves B01J3/04; Heat insulating devices
• CPC Class Codes: F04B 43/043 : Micropumps
• CPC Class Codes: F04B 43/14 : having plate-like flexible members
• CPC Class Codes: F16K 2099/0084 : Chemistry or biology, e.g. "lab-on-a-chip" technology
• CPC Class Codes: F16K 2099/0094 : Micropumps
• CPC Class Codes: F16K 99/0001 : Microvalves microdevices B81B1/00; manufacture or treatment of devices or systems in or on a substrate B81C1/00; microfluidic structures B01L3/5027; micropumps F04B19/006
• CPC Class Codes: F16K 99/0015 : Diaphragm or membrane valves
• CPC Class Codes: F16K 99/0059 : actuated by a pilot fluid
• CPC Class Codes: G01N 1/28 : Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Qmounting specimens on microscopic slides G02B21/34; means for supporting the objects or the materials to be analysed in electron microscopes H01J37/20 ; laboratory gas handling apparatus B01L5/00
• CPC Class Codes: Y10T 137/0324 : With control of flow by a condition or characteristic of a fluid
• CPC Class Codes: Y10T 436/117497 : with a continuously flowing sample or carrier stream
• CPC Class Codes: Y10T 436/2575 : Volumetric liquid transfer

Abstract

The systems and methods described herein include a microfluidic chip having a plurality of microfeatures interconnected to provide a configurable fluid transport system for processing at least one reagent. Inserts are provided to removably interfit into one or more of the microfeatures of the chip, wherein the inserts include sites for interactions with the reagent. As will be seen from the following description, the microfluidic chip and the inserts provide an efficient and accurate approach for conducting parallel assays.

Claims

1. A microfluidic device, comprising:

a substrate having a plurality of channels disposed therein;

at least one reagent reservoir of a type capable of holding a material; and

a distribution valve adapted to controllably direct a flow of the material from the at least one reagent reservoir to a plurality of outlet reservoirs via at least one of the channels coupled to the distribution valve.

2. The device of claim 1, wherein the substrate is a plastic substrate having the plurality of channels etched therein and the at least one reagent reservoir removably coupled to a top surface of the plastic substrate for introducing the material to at least one of the plurality of channels.

3. The device of claim 1, wherein the distribution valve is coupled to at least one bi-directional pump to transport the material from the at least one reagent reservoir to at least one of the plurality of outlet reservoirs via an actuation of the pump.

4. The device of claim 1, further comprising at least one insert configured to inter-fit within at least one of the channels and having a reaction surface for interacting with the material.

5. The device of claim 1, further comprising at least one reagent valve having open and closed states and fluidly couples the at least one reagent reservoir to the plurality of outlet reservoirs via the distribution valve.

6. The device of claim 1, further comprising at least one bi-directional pump associated with at least one of the channels.

7. The device of claim 6, wherein the bi-directional pump includes at least three independently actuatable valve structures being connected in series by respective ones of the channels.

8. The device of claim 6, wherein the at least one of the channels connects a first reservoir and a second reservoir, and the at least one bi-directional pump is adapted to shuttle the material in a first direction towards the first reservoir and in a second direction towards the second reservoir.

9. The device of claim 1, further comprising a plurality of bi-directional pumps associated with respective ones of the channels, wherein

the distribution valve fluidly couples to respective ones of the channels via corresponding ones of the bi-directional pumps, and,

when in a closed state, the distribution valve substantially prevents fluid communication among the channels and between the at least one reagent reservoir and the channels

10. The device of claim 1, further comprising a cartridge adapted to detachably couple to the substrate and has the at least one reagent reservoir disposed thereon for porting the material into the plurality of channels disposed in the substrate.

11. The device of claim 4, wherein

the insert removably inter-fits within a void volume of the at least one of the channels, wherein

a gap is provided between the reaction surface of the insert and a surface of the void volume suitable for allowing the material to pass therethrough.

12. The device of claim 11, wherein the void volume is adapted to receive the insert from an opening of at least one reservoir fluidly coupled to the void volume, wherein a width of the void volume is at least about equal to a width of the insert.

13. The device of claim 11, wherein the void volume is adapted to receive the insert from an opening of the void volume, and a lid member is provided for removably covering the opening.

14. The device of claim 4, wherein the insert comprises a membrane.

15. The device of claim 14, wherein the insert further comprises at least one membrane disk disposed over an aperture of an adhesive layer of the membrane.

16. The device of claim 15, wherein the aperture is one of a circular shape and a shape comprising a circular region and two opposing rectangular regions open to the circular region.

17. The device of claim 15, wherein the membrane disk is applied with at least one of a chemical agent and a biological agent.

18. The device of claim 15, wherein the membrane disk is made from one of nitrocellulose, PVDF, polystyrene, and nylon.

19. The device of claim 1, wherein the substrate includes a plurality of laminated layers having the plurality of the channels disposed in at least one of the layers.

20. The device of claim 1, wherein the material is one of a fluid material, a gaseous material, a solid material that is substantially dissolved in a fluid material, a slurry material, an emulsion material, and a fluid material with particles suspended therein.

21. The device of claim 1, further comprising at least one heating element for adjusting a temperature of the material.

22. The device of claim 1, further comprising:

at least one pump having a plurality of independently actuatable valve structures, and

a programmable controller capable of pneumatically actuating the valve structures for directing a material flow from the at least one reagent reservoir to the plurality of outlet reservoirs via at least one of the channels coupled to the distribution valve.

23. A microfluidic device, comprising:

a substrate having a plurality of channels disposed therein;

a reagent chip having a plurality of reservoirs disposed thereon for fluidly communicating with respective ones of the plurality of the channels in the substrate; and

a ducting chip for porting a fluid material from the reservoirs to the channels in the substrate via a plurality of ducting channels in the ducting chip.

24. The device of claim 23, wherein the reagent chip further includes:

a loading chip having a distribution valve disposed therein; and

a cartridge detachably coupled to the loading chip and has the reservoirs disposed thereon, wherein

the distribution valve directs the fluid material from the reservoirs to the plurality of channels in the substrate via the ducting channels.

25. The device of claim 23, further comprising a plurality of substrates coupled to the reagent chip, wherein the fluid material is ported from the reservoirs to a plurality of channels disposed in at least one of the plurality of substrates.

26. A method for conducting a biological assay, comprising:

providing a microfluidic device comprising a substrate and at least one channel disposed therein,

inter-fitting at least one insert within the channel,

flowing at least one fluid material through the channel to contact the insert therein,

drawing the fluid material away from the insert, and

detecting an interaction on the insert.

27. The method of claim 26, wherein flowing the at least one fluid material comprises actuating a distribution valve to flow a reagent from a reagent reservoir to a plurality of outlet reservoirs.

28. The method of claim 26, wherein flowing the at least one fluid material comprises repeatedly shuttling the fluid material in a first direction towards a first reservoir connected to the channel and in a second direction towards a second reservoir connected to the channel, wherein

a distribution valve coupled to the channel substantially confines the fluid material in the channel when the distribution valve is in a closed state.

29. The method of claim 26, wherein drawing the fluid material away from the insert comprises flowing the fluid material in at least one of a first direction towards a first reservoir connected to the channel and a second direction towards a second reservoir connected to the channel.

30. The method of claim 26, further comprising transporting waste from the channels to a reservoir on the substrate.

31. The method of claim 26, wherein detecting an interaction comprises generating a color intensity value corresponding to at least one sample of the insert.

32. The method of claim 31, wherein generating a color intensity value comprises:

digitizing a color corresponding to the sample to generate a plurality of pixels,

providing a plurality of numerical values for respective ones of the plurality of pixels, and

averaging the plurality of numerical values to provide the color intensity value.

33. The method of claim 31, further comprising computing a threshold value and comparing the color intensity value to the threshold value to detect the interaction.

34. The method of claim 33, further comprising storing at least one of the color intensity value and the threshold value in a database.

35. The method of claim 33, wherein the threshold value is computed using at least one negative control sample.