# US 7,611,840 B2 · Method and device for the treatment of biological samples

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- Number: US 7,611,840 B2
- Document ID: US7611840B2
- Status: Granted
- Kind: B2
- Application number: 10/910,961
- Filed: 2004-08-03
- Published: 2006-02-09
- Granted: 2009-11-03
- Earliest claimed: 2004-08-03
- Assignees: Agency for Science, Technology and Research
- Inventors: Guolin Xu; Pei-Lin Mao; Yuan Hong Yu; Eng Hock Francis Tay
- Web page: https://patentgrep.com/patent/US7611840B2

## CPC

- G01N 1/286: {involving mechanical work, e.g. chopping, disintegrating, compacting, homogenising (microtomes G01N1/06; pulverising in general B02C; mixing in general B01F)}
- C12M 45/07: {by electrical or electromagnetic forces}
- C12M 47/06: {Hydrolysis; Cell lysis; Extraction of intracellular or cell wall material (lysis of microorganisms C12N1/06; extracting or separating nucleic acids from biological samples C12N15/1003)}
- 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)
- 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}

## Abstract

A device for sample tissue disruption and/or cell lysis comprising: a piezoelectric material; and at least a second material in contact with the piezoelectric material; and wherein the second material has an uneven surface on an opposite side to that in contact with the piezoelectric material. The device may be made by assembling at least three layers and membranes for the valves and pumps. The piezoelectric material is actuated by an external voltage source to generate cavitation, which disrupts tissue and/or lyses cells, in particular by a modulated alternative external voltage. The invention further provides a method of disrupting tissue and/or lysing cells in a device. Also provided is a piezoelectric device comprising a piezoelectric material in contact with a second material, and wherein the second material has an uneven surface on an opposite side to that in contact with the piezoelectric material.

## Claims

### Claim 1

A device for sample tissue disruption and/or cell lysis comprising: a piezoelectric material; and at least a second material in contact with the piezoelectric material; wherein the second material has an uneven surface on an opposite side to that in contact with the piezoelectric material, wherein the uneven surface is brought about by a layer of silica beads and contacts a biological sample.

### Claim 2 (depends on 1)

The device of claim 1, wherein the second material is glued or fastened to the piezoelectric material.

### Claim 3 (depends on 1)

The device of claim 1, wherein the silica beads have a diameter between 100 and 400 μm.

### Claim 4 (depends on 1)

The device of claim 1, wherein the second material has a Young's modulus of between 50 to 220 GPa.

### Claim 5 (depends on 1)

The device of claim 1, wherein the piezoelectric material is in the form of a disc, rod or bar or has a planar shape with at least 3 sides.

### Claim 6 (depends on 1)

The device of claim 1, wherein the device is disposable.

### Claim 7 (depends on 1)

The device of claim 1, wherein the device is a cartridge.

### Claim 8 (depends on 7)

The device of claim 7, wherein the cartridge further comprises an inlet port, and outlet port, and at least one chamber.

### Claim 9 (depends on 7)

The device of claim 7, wherein the cartridge is integrated into a bio chip.

### Claim 10 (depends on 1)

The device of claim 1, wherein the device is a biochip device and further comprises:
a dissociation chamber;
reagent and buffer reservoir(s);
one or more valves;
one or more pumps; and
channels connecting the chamber, reservoir(s) and valve(s).

### Claim 11 (depends on 10)

The device of claim 10, wherein the device further comprises a binding and mixing chamber and/or an extraction/elute/PCR chamber.

### Claim 12 (depends on 11)

The device of claim 11, wherein the binding and mixing chamber comprises a piezoelectric material and a second material in contact with the piezoelectric material.

### Claim 13 (depends on 11)

The device of claim 11, wherein the extraction/elute/PCR chamber is deposited with magnetic material.

### Claim 14 (depends on 11)

The device of claim 11, wherein the binding and mixing chamber comprises beads coated with at least one linker for binding to nucleic acid molecules.

### Claim 15 (depends on 14)

The device of claim 14, wherein the beads are magnetic beads.

### Claim 16 (depends on 10)

The device of claim 10, wherein the valves are microvalves.

### Claim 17 (depends on 16)

The device of claim 16, wherein the microvalves comprise membrane microvalves made of material including poly(dimethylsiloxane) (PDMS).

### Claim 18 (depends on 10)

The device of claim 10, wherein the pump is a micropump and comprises a membrane.

### Claim 19 (depends on 18)

The device of claim 18, wherein the membrane is made of material including poly(dimethylsiloxane) (PDMS).

### Claim 20 (depends on 10)

The device of claim 10, wherein the biochip is composed of at least three layers, one or more membranes for the valves and one or more membranes for the pumps, and wherein the first layer comprises at least the dissociation chamber, reagent and buffer reservoir(s), the second layer comprises at least the piezoelectric material, and wherein the valves and the pumps are found at an interface between the second and third layers, and the channels are found at the interfaces of the first and second, and the second and third layers.

### Claim 21 (depends on 20)

The biochip of claim 20, further comprising a cover to put over the first layer.

### Claim 22

A method of disrupting tissue and/or lysing cells in a device, comprising the steps of:
loading a sample and reagents in a device;
actuating a piezoelectric material of the device, wherein the piezoelectric material is in contact with a second material, wherein the second material has an uneven surface on an opposite side to that in contact with the piezoelectric material, the uneven surface contacting the sample, and wherein the uneven surface is brought about by a layer of silica beads;
obtaining disrupted tissue and/or lysed cells; and
recovering the eluate.

### Claim 23 (depends on 22)

The method of claim 22, wherein the silica beads have a diameter between 100 and 400 μm.

### Claim 24 (depends on 22)

The method of claim 22, wherein the piezoelectric material is actuated by an external voltage source.

### Claim 25 (depends on 24)

The method of claim 24, wherein the external voltage source supplies a variable frequency voltage to actuate the piezoelectric material.

### Claim 26 (depends on 22)

The method of claim 22, wherein the sample is an animal, human, plant, or adipose-originated tissue and/or cell sample.

### Claim 27 (depends on 26)

The method of claim 26, wherein the sample is fresh or frozen tissue and/or cell sample.

### Claim 28 (depends on 22)

The method of claim 22, further comprising the steps of isolating, purifying and/or amplifying nucleic acids obtained from the disrupted tissue and lysed cells, and recovering the nucleic acids.

### Claim 29 (depends on 28)

The method of claim 28, wherein the nucleic acids are recovered from the disrupted and/or lysed cells by adding beads coated with at least one linker, and wherein the binding of the linker on the beads to the nucleic acids is carried out by actuating a second piezoelectric material to increase the mixing and binding efficiency, and recovering nucleic acids linked to the beads.

### Claim 30

A piezoelectric device comprising a piezoelectric material, which is in contact with at least a second material; wherein the second material has an uneven surface on an opposite side to that in contact with the piezoelectric material, wherein the uneven surface is brought about by a layer of silica beads, and wherein the uneven surface contacts a biological sample.

### Claim 31 (depends on 30)

The piezoelectric device of claim 30, wherein the silica beads have a diameter between 100 and 400 μm.

### Claim 32 (depends on 30)

The piezoelectric device of claim 30, wherein the second material has a Young's modulus of between 50 to 220 GPa.

### Claim 33 (depends on 30)

The piezoelectric device of claim 30, wherein the piezoelectric material is in the form of a disc, rod or bar or has a planar shape with at least 3 sides.