# US 10,767,153 B2 · Mechanical bioreactor

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- Number: US 10,767,153 B2
- Document ID: US10767153B2
- Status: Granted
- Kind: B2
- Application number: 15/759,388
- Filed: 2016-08-19
- Published: 2018-09-06
- Granted: 2020-09-08
- Earliest claimed: 2015-08-19
- Assignees: The University Court of the University of Glasgow; University of the West of Scotland
- Applicants: The University Court of the University of Glasgow; University of the West of Scotland
- Inventors: Matthew Dalby; Habib Nikukar; Gabriel Pemberton; Adam Curtis; Stuart Reid; Peter Childs
- Web page: https://patentgrep.com/patent/US10767153B2

## CPC

- C12M 35/04: {Mechanical means, e.g. sonic waves, stretching forces, pressure or shear stimuli}
- C12M 21/08: {for producing artificial tissue or for ex-vivo cultivation of tissue (prostheses A61F2/00, grafts A61L27/00)}
- C12M 23/12: {Well or multiwell plates (C12M25/04 takes precedence)}
- C12M 41/46: {of cellular or enzymatic activity or functionality, e.g. cell viability}
- C12M 27/16: {Vibrating; Shaking; Tilting}
- 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 mechanical bioreactor for transferring vibrations to cell cultures for the purpose of stimulating various biological processes across a relatively large (relative to the amplitude of the vibrations) sample receiving surface. This bioreactor allows multiple samples to receive identical stimulation, which may enable the process to be significantly scaled up. The invention may be particularly applicable to nanoscale vibration amplitudes, where it is non-trivial to design a device that performs this function, because many materials exhibit natural deformation on a scale that would mask or inhibit transfer of nanoscale vibration energy.

## Claims

### Claim 1

An apparatus comprising:
an array of vibration actuators; and
a sample receiving plate vibratably coupled to the array of vibration actuators,
wherein the array of vibration actuators is arranged to vertically oscillate the sample receiving plate at nanoscale amplitudes,
wherein the sample receiving plate has a plurality of sample mounting locations, and wherein the sample receiving plate is configured to:
provide physical engagement to a sample container at each of the plurality of sample mounting locations, and
transmit mechanical vertical vibrations having a substantially uniform nanoscale amplitude across the plurality of sample mounting locations.

### Claim 2 (depends on 1)

The apparatus of claim 1, wherein the sample receiving plate is mounted on the array of vibration actuators.

### Claim 3 (depends on 1)

The apparatus of claim 1, wherein each vibration actuator is adhered to the sample receiving plate.

### Claim 4 (depends on 1)

The apparatus of claim 1, wherein each vibration actuator is part of a respective sample container.

### Claim 5 (depends on 1)

The apparatus of claim 1 including a base block, wherein the array of vibration actuators is mounted on an upper surface of the base block, whereby the sample receiving plate is vibratable relative to the base block.

### Claim 6 (depends on 5)

The apparatus of claim 5, wherein the array of vibration actuators is arranged to oscillate the sample receiving plate in a direction normal to the upper surface of the base block.

### Claim 7 (depends on 1)

The apparatus of claim 1, wherein the sample receiving plate is secured in unbroken physical contact with the sample container.

### Claim 8 (depends on 1)

The apparatus of claim 1, wherein the sample receiving plate is magnetically couplable to the sample container.

### Claim 9 (depends on 8)

The apparatus of claim 8, wherein the sample receiving plate has a multilayer construction comprising a rigid lower layer and a magnetically sensitive upper layer.

### Claim 10 (depends on 9)

The apparatus of claim 9, wherein the upper layer is stainless steel.

### Claim 11 (depends on 9)

The apparatus of claim 9, wherein the lower layer is aluminium.

### Claim 12 (depends on 1)

The apparatus of claim 1, further comprising a sample container having a plurality of wells for receiving biological tissue samples, wherein the sample container has a magnetic undersurface for engaging the sample receiving plate, whereby the plurality of wells are positioned at the plurality of sample mounting locations.

### Claim 13 (depends on 12)

The apparatus of claim 12, wherein the magnetic undersurface comprises a magnetic disk mounted at the base of each of the plurality of wells.

### Claim 14 (depends on 1)

The apparatus of claim 1, further comprising a generator arranged to deliver an oscillating drive signal to each vibration actuator.

### Claim 15 (depends on 14)

The apparatus of claim 14, wherein each vibration actuator comprises a piezoelectric element, whereby application of the oscillating drive signal across the piezoelectric element causes periodic deformation of the actuator.

### Claim 16 (depends on 14)

The apparatus of claim 14, wherein the array of vibration actuators consists of a plurality of actuators connected in series with the generator.

### Claim 17 (depends on 16)

The apparatus of claim 16, wherein the generator comprises a voltage source and an oscillator.

### Claim 18 (depends on 17)

The apparatus of claim 17, wherein the voltage source has an adjustable output voltage for controlling the vibration amplitude of the array of actuators.

### Claim 19 (depends on 14)

The apparatus of claim 14, wherein the array of vibration actuators consists of a plurality of actuators connected to the generator in parallel.

### Claim 20 (depends on 19)

The apparatus of claim 19, wherein the generator comprises an amplifier.

### Claim 21 (depends on 20)

The apparatus of claim 20, wherein the amplifier has an adjustable amplifier volume for controlling the vibration amplitude of the array of vibration actuators.
