# US 11,077,437 B2 · Microfluidic system

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- Number: US 11,077,437 B2
- Document ID: US11077437B2
- Status: Granted
- Kind: B2
- Application number: 16/342,940
- Filed: 2017-10-18
- Published: 2020-02-20
- Granted: 2021-08-03
- Earliest claimed: 2016-10-18
- Assignees: Menarini Silicon Biosystems S.p.A.
- Applicants: Menarini Silicon Biosystems S.p.A.
- Inventors: Gianni Medoro; Alex Calanca
- Web page: https://patentgrep.com/patent/US11077437B2

## CPC

- B01L 3/502707: {characterised by the manufacture of the container or its components}
- 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}
- B01L 3/50273: {characterised by the means or forces applied to move the fluids}
- B01L 7/00: Heating or cooling apparatus (autoclaves B01J3/04); Heat insulating devices
- B01L 2200/0652: Sorting or classification of particles or molecules
- B01L 2300/047: Additional chamber, reservoir
- B01L 2300/0627: Sensor or part of a sensor is integrated
- B01L 2300/0645: Electrodes
- B01L 2300/0663: Whole sensors
- B01L 2300/0809: rectangular shaped
- B01L 2300/0816: Cards, e.g. flat sample carriers usually with flow in two horizontal directions
- B01L 2300/0883: Serpentine channels
- B01L 2300/1822: using Peltier elements
- B01L 2300/185: using a liquid as fluid
- B01L 2300/1894: Cooling means; Cryo cooling
- B01L 2400/0415: electrical forces, e.g. electrokinetic
- B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE

## Abstract

A microfluidic system for the isolation of particles of at least one given type belonging to a sample and comprising a separation unit, which is designed to transfer the particles of given type from a main chamber to a recovery chamber in a substantially selective manner with respect to further particles of the sample; at least one first reservoir, which is designed to contain a liquid and is fluidically connected to the separation unit; and a regulating assembly, which comprises at least a first regulating device having a first heat transfer element arranged at the first reservoir to adjust the temperature of the first reservoir, in particular to absorb heat from the reservoir.

## Claims

### Claim 1

A microfluidic system for the isolation of particles of at least one given type from a sample; the microfluidic system comprising:
an inlet, through which, in use, the sample is introduced into the microfluidic system;
a separation unit which comprises a main chamber and a recovery chamber and which is configured to transfer at least part of the particles of the given type from the main chamber to the recovery chamber in a selective manner with respect to further particles of the sample;
at least one first reservoir having an inner volume of at least 1 μL, which is designed to contain a liquid and is fluidically connected to the separation unit; and at least one actuator configured to move the liquid from the first reservoir to the separation unit;
the microfluidic system being characterized in that it comprises a regulating assembly, which comprises at least one first regulating device having at least one first heat transfer element which is arranged at the first reservoir, such that the at least first heat transfer element is configured to absorb heat from the first reservoir itself; the separation unit comprising a system selected from the group consisting of dielectrophoresis, optical tweezers, magnetophoresis, acoustophoresis and a combination thereof.

### Claim 2 (depends on 1)

The microfluidic system according to claim 1, wherein the regulating assembly comprises a control device which is designed to control the first regulating device so as to adjust the temperature of the first heat transfer element and so as to maintain the temperature of the first heat transfer element in a defined temperature range.

### Claim 3 (depends on 1)

The microfluidic system according to claim 1, wherein the regulating assembly comprises a temperature sensor to detect the temperature of the first heat transfer element; and a control device designed to control the first regulating device according to the parameters detected by the temperature sensor so as to adjust the temperature of the element.

### Claim 4 (depends on 1)

The microfluidic system according to claim 1, wherein the regulating assembly comprises at least a second regulating device having at least a second heat transfer element, which is arranged in the area of the separation unit to adjust the temperature of the main chamber and the recovery chamber.

### Claim 5 (depends on 4)

The microfluidic system according to claim 4, and comprising a control device, which is designed to control the first and the second regulating device independently from each other.

### Claim 6 (depends on 5)

The microfluidic system according to claim 5, wherein the control device comprises a first and a second control unit independent of each other; the first control unit is designed to control the first regulating device; the second control unit is designed to control the second regulating device.

### Claim 7 (depends on 4)

The microfluidic system according to claim 4, further comprising a microfluidic device which, in turn, comprises the main chamber, the recovery chamber and the first reservoir; the first and the second heat transfer element are arranged on opposite sides of the microfluidic device.

### Claim 8 (depends on 7)

The microfluidic system according to claim 7, wherein the second heat transfer element is arranged in contact with the microfluidic device;
the first heat transfer element is arranged at a distance of less than 500 pm from the microfluidic device.

### Claim 9 (depends on 1)

The microfluidic system according to claim 1, further comprising at least one second reservoir, which fluidically connects the inlet to the separation unit and is designed to contain at least part of the sample; the first reservoir being fluidically connected to the recovery chamber; the first heat transfer element being arranged at the first and the second reservoir and the second reservoir is arranged between the inlet and the main chamber and fluidically connects the inlet to the main chamber.

### Claim 10 (depends on 9)

The microfluidic system according to claim 9, further comprising at least one first duct, which is fluidically connected to the main chamber (4) to receive liquid coming from the main chamber; at least one outlet, which is fluidically connected to the recovery chamber and through which, in use, at least part of the particles of the given type collected in the recovery chamber flow; and at least one second duct for fluidically connecting the recovery chamber to the outlet.

### Claim 11 (depends on 10)

The microfluidic system according to claim 10, further comprising a microfluidic device, which comprises the main chamber, the recovery chamber, the first, the second reservoir and the first and second duct; in use, at least part of the particles of the given type collected in the recovery chamber flow out of the microfluidic device through said outlet.

### Claim 12 (depends on 7)

The microfluidic system according to claim 7, further comprising an apparatus for the manipulation of particles which is provided with a seat housing the microfluidic device, which comprises first electrical connectors designed to electrically connect the apparatus to the microfluidic device and which is movable between an opening position and a closing position; the microfluidic device has further electrical connectors which are coupled to the first electrical connectors in a separable manner and can be removed from the apparatus when the seat is in the opening position; the apparatus comprising the actuator and the regulating assembly.

### Claim 13 (depends on 1)

The microfluidic system according to claim 1, wherein the separation unit comprises an electrodes system for selective movement of the particles.

### Claim 14 (depends on 1)

The microfluidic system according to claim 1, wherein the regulating device for the transfer of heat has a through opening in the area of the separation unit to allow what happens in the separation unit to be monitored.

### Claim 15 (depends on 1)

The microfluidic system according to claim 1, wherein the regulating assembly comprises a sensor for detecting the temperature of the first heat transfer element and a control device for controlling the first regulating device depending on the parameters detected by the sensor, so as to adjust the temperature of the first heat transfer element to keep the temperature of the first heat transfer element at one or more defined values.

### Claim 16 (depends on 1)

The microfluidic system according to claim 1, wherein the regulating assembly comprises the first and at least a second regulating device; the first regulating device is arranged at the first reservoir, to adjust the temperature thereof; the second regulating device is arranged at the second reservoir, to adjust the temperature thereof; the system comprises a control device, which is designed to control the first and the second regulating device independently of each another.

### Claim 17 (depends on 1)

The microfluidic system according to claim 1, wherein the regulating assembly comprises a heat pump for absorbing heat from the first heat transfer element; the heat pump comprises a Peltier cooler.

### Claim 18 (depends on 1)

The microfluidic system according to claim 1, wherein the first regulating device comprises a heat exchanger and a cooling circuit, through which, in use, a cooling liquid flows.

### Claim 19

An apparatus, comprising; a seat designed to house a microfluidic device that comprises a main chamber, a recovery chamber and a first reservoir designed to contain a liquid, wherein the seat is movable between an open position and a closed position;
first electrical connectors configured to electrically connect the apparatus to the microfluidic device;
at least one actuator configured to move the liquid from the first reservoir to the main chamber; and
a regulating assembly, which comprises at least one first regulating device having at least one first heat transfer element which is arranged at a first reservoir, wherein the at least first heat transfer element is configured to absorb heat from the first reservoir.

### Claim 20 (depends on 4)

The microfluidic system of claim 4, wherein the second heat transfer element absorbs heat from the main chamber and from the recovery chamber.

### Claim 21 (depends on 5)

The microfluidic system of claim 5, wherein the control device is designed to adjust the temperature of the first and the second heat transfer element independently of each other.

### Claim 22 (depends on 7)

The microfluidic system of claim 7, wherein the first and the second heat transfer element are arranged above and below the microfluidic device.
