# US 7,745,211 B2 · Integrated microfluidic control employing programmable tactile actuators

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- Number: US 7,745,211 B2
- Document ID: US7745211B2
- Status: Granted
- Kind: B2
- Application number: 10/548,692
- Filed: 2004-03-10
- Published: 2006-07-27
- Granted: 2010-06-29
- Earliest claimed: 2003-03-10
- Assignees: The Regents of the University of Michigan
- Inventors: Shuichi Takayama; Xiaoyue Zhu; Wei Gu; Gary Daniel Smith; Yunseok Heo; Brenda S. Cho; Nobuyuki Futai
- Web page: https://patentgrep.com/patent/US7745211B2

## CPC

- 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)}
- C12M 23/16: {Microfluidic devices; Capillary tubes (integrated microfluidic structures B01L3/5027; microreactors B01J19/0093)}
- 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)}
- F16K 99/0026: {Valves using channel deformation}
- F16K 99/0048: {using piezoelectric means}
- G09B 23/12: of liquids or gases
- B01J 2219/00396: Membrane valves
- B01J 2219/00891: Feeding or evacuation
- B01L 2200/10: Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
- B01L 2200/12: Specific details about manufacturing devices
- B01L 2200/143: Quality control, feedback systems
- B01L 2300/025: Displaying results or values with integrated means
- B01L 2300/044: pierceable, e.g. films, membranes
- B01L 2300/0816: Cards, e.g. flat sample carriers usually with flow in two horizontal directions
- B01L 2300/0867: Multiple inlets and one sample wells, e.g. mixing, dilution
- B01L 2300/0877: Flow chambers
- B01L 2300/0887: Laminated structure
- B01L 2300/123: Flexible; Elastomeric
- B01L 2400/0481: squeezing of channels or chambers
- B01L 2400/0638: membrane valves, flap valves
- B01L 2400/0655: pinch valves
- F16K 2099/0074: {using photolithography, e.g. etching}
- F16K 2099/0078: {using moulding or stamping}
- F16K 2099/008: {Multi-layer fabrications}
- F16K 2099/0084: {Chemistry or biology, e.g. "lab-on-a-chip" technology}
- 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}
- F16K: VALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING {(devices for emptying and evacuating the excess liquid in valves or conduits F16L55/07)}
- G09B: EDUCATIONAL OR DEMONSTRATION APPLIANCES; APPLIANCES FOR TEACHING, OR COMMUNICATING WITH, THE BLIND, DEAF OR MUTE; MODELS; PLANETARIA; GLOBES; MAPS; DIAGRAMS (devices for psychotechnics or for testing reaction times A61B5/16; games, sports, amusements A63; projectors, projector screens G03B)
- B01J: CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS

## Abstract

Microfluidic devices having active features such as valves, peristaltic pumps, and mixing portions are fabricated to have a thin elastomeric membrane over the active features. The active features are activated by a tactile actuator external to the membrane, for example, a commercial Braille display. The display may be computer controlled, for example by simple text editor software, to activate individual Braille protrusions or a plurality of protrusions to actuate the active portions of the microfluidic device. Integral devices can incorporate the tactile actuators in a single device, but still external to the membrane.

## Claims

### Claim 1

A device suitable for the culture of a living organism in a fluid wherein the fluid composition is supplied as a flow of fluid, said device comprising a microfluidics device comprising a substrate having therein at least one empty space whose shape and/or volume is desired to be altered, said empty space defined on one side thereof by a deformable elastomer layer; and an electronically addressable tactile actuator proximate a side of said elastomer layer, said tactile actuator having a plurality of spaced apart individually addressable extendable protrusions, at least one of which, when actuated, bears upon said deformable elastomer layer, deforming said layer, and altering the shape and/or volume of said empty space, wherein at least one empty space comprises a growth chamber for said organism, said growth chamber in fluid communication with at least one reservoir, and at least one fluid pumping portion, said fluid pumping portion comprising a flow channel and, said tactile actuator programmed to extend and retract said protrusions independently from each other in a sequence which causes liquid to be pumped through said flow channel, and wherein the width of each addressable extendable protrusion is larger than the width of said flow channel, and wherein said addressable extendable protrusions restrict or close said flow channel when actuated, said flow channel communicating with said reservoir and said growth chamber, such that fluid flows from said reservoir through said growth chamber.

### Claim 2 (depends on 1)

The device of claim 1, comprising a plurality of reservoirs, each of said reservoirs having associated therewith a valved flow channel in fluid communication with said growth chamber, such that flow of fluid into said growth chamber may be selected from one or a plurality of reservoirs.

### Claim 3 (depends on 1)

The device of claim 1, wherein said microchannel has a depth of from 10 μm to 40 μm, and wherein said elastomeric layer has a thickness of from 100 μm to 400 μm.

### Claim 4 (depends on 1)

The device of claim 1, wherein said substrate is an elastomeric material.

### Claim 5 (depends on 1)

The device of claim 1, wherein said substrate and said elastomeric layer both comprise a silicone elastomer.

### Claim 6 (depends on 1)

The device of claim 1, wherein said growth chamber comprises a portion that is at least partially bell-shaped, wherein said bell-shaped passage comprises two parallel sides that are flat and two parallel sides that are rounded and smooth.

### Claim 7 (depends on 1)

The device of claim 1, wherein said growth chamber is located in a portion of said device not contacted by said addressable extendable protrusions.

### Claim 8 (depends on 1)

A process for the culture of organisms, comprising introducing said organism or a precursor thereof into an empty space in a device of claim 1, and pumping a growth medium fluid past said organism by means of a microchannel peristaltic pump operated by said tactile actuator.

### Claim 9 (depends on 8)

The process of claim 8, wherein said device contains a plurality of fluid reservoirs, and a plurality of associated valved microchannels, such that the fluid pumped past the organism can be derived from one or more selected reservoirs by opening and/or closing selected valves by means of said tactile actuator.

### Claim 10 (depends on 9)

The process of claim 9, wherein each valved microchannel further comprises a peristaltic pump.

### Claim 11 (depends on 9)

The process of claim 9, where the flow rate of fluid past said organism is varied by means varying the rate of actuation of sequentially positioned extendable protrusions along a microchannel in fluid communication with the empty space containing said organism.

### Claim 12 (depends on 11)

The process of claim 11, wherein the fluid flowing is altered by closing or opening respective microchannel valves associated with a plurality of fluid supply microchannels.

### Claim 13 (depends on 10)

The process of claim 10, wherein said geometric array is a Braille display, and said individual protrusions are actuated by supplying an ASCII character to said display.

### Claim 14 (depends on 8)

The process of claim 8, wherein said living organism is an embryo.

### Claim 15 (depends on 14)

The process of claim 14, wherein said embryo is sustained for a period of up to three weeks.

### Claim 16 (depends on 1)

A process for implementing fluid control in a microfluidics device, comprising selecting a microfluidics device of claim 1, selecting as said tactile actuator a geometric array of extendable protrusions, and actuating individual extendable protrusions in said geometric array by means of a computer program.

### Claim 17 (depends on 16)

The process of claim 16, wherein said living organism is an embryo.

### Claim 18 (depends on 17)

The process of claim 17, wherein said embryo is sustained for a period of up to three weeks.