# US 2010/0167384 A1 · Microfluidic mixing and analytical apparatus

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- Number: US 2010/0167384 A1
- Document ID: US20100167384A1
- Status: Published application
- Kind: A1
- Application number: 12/685,546
- Filed: 2010-01-11
- Published: 2010-07-01
- Earliest claimed: 2005-11-30
- Assignees: Micronics, Inc.
- Inventors: John Clemmens; C. Frederick Battrell; John Gerdes; Denise Maxine Hoekstra
- Web page: https://patentgrep.com/patent/US20100167384A1

## CPC

- B01F 33/30: Micromixers
- B01F 31/65: the materials to be mixed being directly submitted to a pulsating movement, e.g. by means of an oscillating piston or air column
- B01L 3/50273: {characterised by the means or forces applied to move the fluids}
- B01L 3/502738: {characterised by integrated valves (throttle valves in microfluidic sample containers B01L3/502746)}
- B01L 3/502761: {specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads or physically stretching molecules}
- C12M 23/16: {Microfluidic devices; Capillary tubes (integrated microfluidic structures B01L3/5027; microreactors B01J19/0093)}
- C12M 23/42: {Integrated assemblies, e.g. cassettes or cartridges}
- C12M 25/16: {Particles; Beads; Granular material; Encapsulation (chemical or physical processes conducted in the presence of fluids and solid particles B01J8/00)}
- C12M 29/10: {Perfusion}
- B01L 3/502723: {characterised by venting arrangements}
- B01L 2300/0816: Cards, e.g. flat sample carriers usually with flow in two horizontal directions
- B01L 2400/0481: squeezing of channels or chambers
- B01L 2400/0655: pinch valves
- G01N 2035/00544: {using fluid flow}
- G01N 2035/00564: {Handling or washing solid phase elements, e.g. beads}
- B01F: MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING (mixing paints B44D3/06)
- B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- C12M: APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; {APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS}
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

Disclosed herein is a device comprising a pair of bellows pumps configured for efficient mixing at a microfluidic scale. By moving a fluid sample and particles in suspension through an aperture between the paired bellows pump mixing chambers, molecular collisions leading to binding between the particles and ligands in the sample are enhanced. Such devices provide an alternative for mixing that does not use a vent and can be used with a variety of particles in suspension such as magnetic beads to capture or purify useful cells and molecules.

## Claims

### Claim at position 1

1-15. (canceled)

### Claim 16

A microfluidic apparatus comprising:
a) a microfluidic cartridge comprising:
i) a first bellows pump with a pump cavity bisected in coronal plane by a first elastomeric diaphragm, said first diaphragm dividing said pump cavity of said first bellows pump into a first half-chamber and a second half-chamber;
ii) a second bellows pump with a pump cavity bisected in coronal plane by a second elastomeric diaphragm, said second diaphragm dividing said pump cavity of said second bellows pump into a first half-chamber and a second half-chamber;
iii) a flow-restricting aperture fluidly interconnecting said first half-chamber of said first bellows pump with said first half-chamber of said second bellow pump, said flow-restricting aperture having a depth, width and length such that fluid flow within the flow-restricting aperture is laminar;
iv) an inlet fluidly connected to said first half-chamber of said first bellows pump, wherein said inlet is comprised of a microfluidic channel with valve; and
v) a pneumatic member pneumatically connected to said second half-chamber of said first bellows pump, wherein said pneumatic element is selected from the group consisting of a microchannel and a vent; and
vi) a pneumatic member pneumatically connected to said second half-chamber of said second bellows pump, wherein said pneumatic element is selected from the group consisting of a microchannel and a vent,
wherein said cartridge is configured to receive pneumatic pulses from a pneumatic pulse generator programmed to actuate the first diaphragm with pneumatic pulses such that fluid flow within the flow-restricting aperture is laminar, but transitions to turbulent flow upon exiting said flow-restricting aperture and into said first half-chambers of said first and second bellows pumps; and
(b) an automated workstation for receiving said microfluidic cartridge, said automated workstation comprising said pneumatic pulse generator and a pneumatic distribution manifold for distributing said pneumatic pulses to said microfluidic cartridge.

### Claim at position 3

17-18. (canceled)

### Claim 19 (depends on 16)

A microfluidic apparatus according to claim 16, further comprising a means for detecting a target analyte in a sample.

### Claim 20

(canceled)

### Claim 21 (depends on 19)

A microfluidic apparatus according to claim 19, wherein said target analyte is selected from the group consisting of eukaryotic cell, bacterial cell, virus, macromolecule, antigen, antibody, epitope, nucleic acid, metabolite, small molecule, and drug.

### Claim at position 7

22-27. (canceled)

### Claim 28 (depends on 16)

A microfluidic apparatus according to claim 16, wherein said pneumatic pulses alternate between positive pressure and suction pressure.

### Claim 29 (depends on 16)

A microfluidic apparatus according to claim 16, wherein said pneumatic pulses are directed in alternation to said first and second bellows pumps.

### Claim at position 10

30-40. (canceled)

### Claim 41 (depends on 28)

A microfluidic apparatus according to claim 28, wherein said pneumatic pulses are directed to said first bellows pump.

### Claim 42 (depends on 16)

A microfluidic apparatus according to claim 16, wherein said automated workstation comprises a pneumatic servomechanism for generating said pneumatic pulses under control of a microprocessor operatively disposed therein.

### Claim 43 (depends on 19)

A microfluidic apparatus of claim 19, wherein said sample is a biological sample.

### Claim 44 (depends on 16)

A microfluidic apparatus of claim 16, wherein said apparatus is configured for performing PCR.

### Claim 45 (depends on 44)

A microfluidic apparatus of claim 44, wherein said automated workstation comprises a thermal interface with a first heating station for heating said first bellows pump to a temperature for melting a nucleic acid target analyte and a second heating station for heating said second bellows pump to a temperature for annealing primers and extending a PCR amplification product.

### Claim 46 (depends on 44)

A microfluidic apparatus of claim 44, wherein said automated workstation further comprises a detection chamber and means for detecting hybridization of a probe to said PCR amplification product.