Microfluidic and nanofluidic devices, systems, and applications

• US 8,557,518 B2
• Filed: 07/28/2010
• Issued: 10/15/2013
• Est. Priority Date: 02/05/2007
• Status: Active Grant

• Current Assignee: IntegenX Inc. (Thermo Fisher Scientific Incorporated)
• Original Assignee: IntegenX Inc. (Thermo Fisher Scientific Incorporated)
• Inventors: Jovanovich, Stevan Bogdan, Blaga, Iuliu I., Nguyen, Michael, Nielsen, William D., Vangbo, Mattias
• Primary Examiner(s): FORMAN, BETTY J
• Application Number:
  US12/845,650
• Publication Number:
  US 20120115189A1
• Time in Patent Office: 1,175 Days
• Field of Search: 435/6.1, 435/91.2, 435/283.1, 435/287.3, 435/288.5, 422/68.1, 422/502
• US Class Current: 435/6.1
• CPC Class Codes: B01L 2200/028 Modular arrangements
• CPC Class Codes: B01L 2200/0668 Trapping microscopic beads
• 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 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• 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 2300/088 Channel loops
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2300/0896 Nanoscaled
• 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 2400/0655 pinch valves
• 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 3/502761 specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules investigating characteristics of particles G01N15/00
• 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: B01L 7/525 with physical movement of samples between temperature zones
• CPC Class Codes: B33Y 80/00 Products made by additive manufacturing
• CPC Class Codes: B82Y 30/00 : Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C12Q 1/686 : Polymerase chain reaction [PCR]
• 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

Abstract

The present invention discloses the integration of programmable microfluidic circuits to achieve practical applications to process biochemical and chemical reactions and to integrate these reactions. In some embodiments workflows for biochemical reactions or chemical workflows are combined. Microvalves such as programmable microfluidic circuit with Y valves and flow through valves are disclosed. In some embodiments microvalves of the present invention are used for mixing fluids, which may be part of an integrated process. These processes include mixing samples and moving reactions to an edge or reservoir for modular microfluidics, use of capture regions, and injection into analytical devices on separate devices. In some embodiments star and nested star designs, or bead capture by change of cross sectional area of a channel in a microvalve are used. Movement of samples between temperature zones are further disclosed using fixed temperature and movement of the samples by micropumps.

Claims

1. A method comprising:

a) providing a microfluidic device comprising;

i) at least one microfluidic circuit, wherein the at least one microfluidic circuit comprises;

(A) a first microfluidic channel;

(B) a first port;

(C) a second port;

(D) a first valve, wherein the first valve has a first position and a second position in which the cross-sectional area of the first valve is increased;

(E) a second channel that converges with the first channel at a nexus, wherein the nexus comprises a valve that, when open, allows for fluid communication between said first and second channels and, when closed, interrupts fluid flow between the first and second channels but not along the first channel, and wherein the second channel is fluidically connected to a third port;

(F) a reactor; and

(G) at least one diaphragm pump comprising at least three diaphragm valves configured to pump fluid from the first port and the third port into the first valve, into the reactor and into the second port; and

ii) a magnet configured to produce a magnetic field within the first valve;

b) pumping reagent from the first port and sample from the third port into the first channel to form a mixture;

c) pumping the mixture into the reactor and performing a chemical or biochemical reaction on the mixture to create a product;

d) contacting the product in the device with particles, wherein the particles bind the product;

e) positioning the first valve in the second position;

f) moving the particles through the first channel into the first valve; and

g) capturing the particles in the first valve with the magnetic field.

2. The method of claim 1, further comprising:

h) washing the particles.

3. The method of claim 2, further comprising:

i) collecting the product.

4. The method of claim 1, wherein the chemical or biochemical reaction comprises PCR, cycle sequencing, isothermal nucleic acid amplification, ligation, restriction, second strand synthesis, transcription, translation, DNA modification, polymerization, DNA-protein binding, addition, cleavage, cyclization or condensation.

5. The method of claim 1, further comprising varying the temperature in the reactor while performing the reaction in the reactor.

6. A microfluidic device comprising:

i) at least one microfluidic circuit, wherein the at least one microfluidic circuit comprises;

(A) a first microfluidic channel;

(B) a first port;

(C) a second port;

(D) a first valve, wherein the first valve has a first position and a second position in which the cross-sectional area of the first valve is increased;

(E) a second channel that converges with the first channel at a nexus,

wherein the nexus comprises a valve that, when open, allows for fluid communication between said first and second channels and, when closed, interrupts fluid flow between the first and second channels but not along the first channel, and wherein the second channel is fluidically connected to a third port;

(F) a reactor; and

(G) at least one diaphragm pump comprising at least three diaphragm valves configured to pump fluid from the first port and the third port into the first valve, into the reactor and into the second port;

ii) a magnet configured to produce a magnetic field within the first valve; and

iii) particles, wherein the particles are configured to move through the first channel into the first valve and to be captured in the first valve by the magnetic field when the first valve is in the second position.

7. The device of claim 6, which is configured to:

a) pump reagent from the first port and sample from the third port into the first channel to form a mixture;

b) pump the mixture into the reactor and perform a chemical or biochemical reaction on the mixture to create a product;

c) contact the product in the device with the particles, wherein the particles bind the product;

d) position the first valve in the second position;

e) move the particles through the first channel into the first valve; and

f) capture the particles in the first valve with the magnetic field.

8. The device of claim 7, which is further configured to:

g) wash the particles.

9. The device of claim 8, which is further configured to:

h) collect the product.

10. The device of claim 7, wherein the chemical or biochemical reaction comprises PCR, cycle sequencing, isothermal nucleic acid amplification, ligation, restriction, second strand synthesis, transcription, translation, DNA modification, polymerization, DNA-protein binding, addition, cleavage, cyclization or condensation.

11. The device of claim 7, wherein the temperature in the reactor is varied while the reaction is performed in the reactor.