# US 2025/0085203 A1 · Off-chip pressure-controlled centrifugal microfluidic fractionation

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- Number: US 2025/0085203 A1
- Document ID: US20250085203A1
- Status: Published application
- Kind: A1
- Application number: 18/462,752
- Filed: 2022-03-09
- Published: 2025-03-13
- Earliest claimed: 2021-03-11
- Assignees: National Research Council of Canada
- Applicants: National Research Council of Canada
- Inventors: Byeong-Ui MOON; Liviu CLIME; Daniel Brassard; Keith MORTON; Teodor VERES
- Web page: https://patentgrep.com/patent/US20250085203A1

## CPC

- G01N 1/4077: {by other techniques involving separation of suspended solids}
- B01L 3/502753: {characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation}
- C12N 15/1006: {by means of a solid support carrier, e.g. particles, polymers}
- B01L 3/502715: {characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces}
- B01L 3/502769: {characterised by multiphase flow arrangements}
- B01L 2200/027: for microfluidic devices
- B01L 2200/0673: Handling of plugs of fluid surrounded by immiscible fluid
- B01L 2200/0684: Venting, avoiding backpressure, avoid gas bubbles
- B01L 2200/16: Reagents, handling or storing thereof
- B01L 2300/0663: Whole sensors
- B01L 2300/0803: Disc shape
- B01L 2300/0864: comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
- B01L 2300/0883: Serpentine channels
- B01L 2300/14: Means for pressure control
- B01L 2400/0409: centrifugal forces
- B01L 2400/0487: fluid pressure, pneumatics
- G01N 2001/4083: {sedimentation}
- 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)
- B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

A technique is provided for incorporating pneumatic control in centrifugal microfluidics. The technique involves providing a chip controller that has pressurized fluid supply lines for coupling one or more pressurized chambers of the controller with ports of a microfluidic chip. At least part of the chip controller is mounted to a centrifuge for rotation with the chip. A flow control device is provided in each supply line for selectively controlling the pressurized fluid supply, and is electrically controlled. Bubble mixing, on and off-chip valving, and switching are demonstrated.

## Claims

### Claim 1

A microfluidic chip controller comprising:
a body having a coupling for mounting to a centrifuge while permitting concurrent mounting of a microfluidic chip to the centrifuge, so that the body and chip are rotatable by the centrifuge; the body having a first opening to a first pressurized fluid supply;
a first pressurized fluid supply line having first and second ends, the first end for fluid communication with the first opening, and the second end adapted for fluid communication with a first port of the chip;
a flow control device for selectively controlling a supplied pressure to the first port; and
an electrical circuit for controlling the flow control device,
whereby the microfluidic chip controller mounted with the chip to the centrifuge, with the first supply line connected to the first port of the chip, allows for controlled delivery of pressurized fluid into the chip during centrifugation.

### Claim 2 (depends on 1)

The microfluidic chip controller of claim 1 wherein the first pressurized fluid supply supplies gas.

### Claim 3 (depends on 1)

The microfluidic chip controller of claim 1 wherein the first pressurized fluid supply supplies a pressurized fluid that has a density that is higher or lower than a microfluid for which the chip is designed, and low miscibility or solubility with the microfluid.

### Claim 4 (depends on 2)

The microfluidic chip controller of claim 2 wherein the gas is an inert gas selected for non-reactivity with reactants and substrates used in an intended process for the chip.

### Claim 5 (depends on 2)

The microfluidic chip controller of claim 2 wherein the gas is a purified or sterilized air, or nitrogen.

### Claim 6 (depends on 2)

The microfluidic chip controller of claim 2 wherein the gas has an absolute pressure of 0.1 to 2.5 atmospheres.

### Claim 7 (depends on 2)

The microfluidic chip controller of claim 2 wherein the gas is at ambient pressure, or has a pressure at least 0.003 atmospheres above or below ambient pressure.

### Claim 8 (depends on 2)

The microfluidic chip controller of claim 2 wherein the gas has a pressure of 1.003 to 1.8 atmospheres.

### Claim 9 (depends on 1, 2, 3, 4, 5, 6, 7, 8)

The microfluidic chip controller of any one of claims 1-8 further comprising a second pressurized fluid supply line communicating with a second pressurized fluid supply by a second opening in the body at a first end, the second supply line providing, at a second end, a coupling for sealed mounting to a second port of the chip.

### Claim 10 (depends on 9)

The microfluidic chip controller of claim 9 wherein the first and second supplies are adapted to be independently maintained at different pressures.

### Claim 11 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10)

The microfluidic chip controller of any one of claims 1-10 wherein the coupling for mounting the control system to a centrifuge provides a mechanical attachment to a blade of a centrifuge at a position that does not interfere with a mounting position for the chip on the blade.

### Claim 12 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10)

The microfluidic chip controller of any one of claims 1-10 wherein the coupling for mounting the control system to a centrifuge provides a mechanical attachment to a chip mounted to a blade of a centrifuge.

### Claim 13 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10)

The microfluidic chip controller of any one of claims 1-10 further comprising a part of the body shaped for mounting or supporting at least a part of the chip.

### Claim 14 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13)

The microfluidic chip controller of any one of claims 1-13 wherein the coupling permits concurrent mounting of a plurality of chips to the centrifuge.

### Claim 15 (depends on 14)

The microfluidic chip controller of claim 14 wherein the first supply line branches, to provide at the second end, a plurality of couplings for fluid connections to first ports respectively on each of the plurality of chips.

### Claim 16 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15)

The microfluidic chip controller of any one of claims 1-15 wherein the electrical circuit further comprises an electrical lead for coupling with an electrical component on the chip adapted to supply power to, or provide signaling to, the electrical component.

### Claim 17 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16)

The microfluidic chip controller of any one of claims 1-16 wherein the microfluidic chip controller further comprises a joint for mounting to the chip or a support for the chip.

### Claim 18 (depends on 17)

The microfluidic chip controller of claim 17 wherein the microfluidic chip controller further comprises a mechanical actuator for controlling a motion of the chip in a plane of rotation of the centrifuge, the motion including at least a 5° rotation of the chip projected on the plane.

### Claim 19 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18)

The microfluidic chip controller of claim any one of claims 1-18 wherein the first pressurized fluid supply comprises an enclosed pressurized chamber.

### Claim 20 (depends on 19)

The microfluidic chip controller of claim 19 wherein the chamber comprises a pressurized chamber in communication with a negative pressure source, or a positive pressure source.

### Claim 21 (depends on 20)

The microfluidic chip controller of claim 20 wherein the negative pressure source or positive pressure source is from a pump.

### Claim 22 (depends on 21)

The microfluidic chip controller of claim 21 wherein the pump is mounted to the chip controller.

### Claim 23 (depends on 22)

The microfluidic chip controller of claim 22 wherein the pump is mounted to the chip controller near a centre of rotation of the centrifuge to limit a moment on a blade of the centrifuge by which the chip controller is mounted.

### Claim 24 (depends on 21, 22, 23)

The microfluidic chip controller of any one of claims 21-23 wherein the electrical circuit is adapted to control the pump.

### Claim 25 (depends on 21, 22, 23, 24)

The microfluidic chip controller of any one of claims 21-24 wherein a power supply for the pump is mounted to the chip controller.

### Claim 26 (depends on 21, 22, 23, 24)

The microfluidic chip controller of any one of claims 21-24 wherein a power supply for the pump is provided off of the centrifuge, and is connected to the pump by an electrical contacting rotational coupling, such as a slip ring.

### Claim 27 (depends on 20)

The microfluidic chip controller of claim 20 wherein the negative pressure source or positive pressure source is provided off of the centrifuge, and the chamber is coupled to the pump via a pneumatic slip ring.

### Claim 28 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27)

The microfluidic chip controller of any one of claims 1-27 wherein the body comprises a rotor of a slip ring mounted for rotation with the centrifuge, wherein the chip controller further comprises a stator of the slip ring.

### Claim 29 (depends on 28)

The microfluidic chip controller of claim 28 wherein the flow control element is affixed to the stator of the slip ring.

### Claim 30 (depends on 28, 29)

The microfluidic chip controller of claim 28 or 29 wherein a plurality of pressurized fluid supply lines on the rotor are coupled to respective pressurized fluid supplies of the stator via multichannel slip rings.

### Claim 31 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30)

The microfluidic chip controller of any one of claims 1-30 wherein at least one electrical contacting rotational coupling couples the electrical circuit with a stationary controller, for supply of control signaling, data, and electrical power.

### Claim 32 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31)

The microfluidic chip controller of any one of claims 1-31 further comprising a sensor mounted to the body and/or the chip, for measuring a property of the chip or a liquid contained therein, the sensor being in electronic communication with the electrical circuit.

### Claim 33 (depends on 32)

The microfluidic chip controller of claim 32 wherein the sensor:
gives feedback regarding a position of a fluid within the chip; or
is a chemical, physical, or electronic sensor, including a temperature sensor, fluid dynamic sensor, or an optical sensor;

### Claim 34 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33)

The microfluidic chip controller of any one of claims 1-33 further comprising an actuator mounted to the body and/or the chip, for measuring a property, the actuator is in electronic communication with the electrical circuit.

### Claim 35 (depends on 34)

The microfluidic chip controller of claim 34 wherein the actuator:
affects a position of a fluid within the chip; or
is a chemical, physical, or electronic device, including a temperature regulator, fluid dynamic regulator, or an optical emitter.

### Claim 36

A method for controlling a pressurized fluid supply in a microfluidic chip, the method comprising:
mounting a microfluidic chip control system to a centrifuge and mounting a microfluidic chip to the centrifuge, so that the chip and at least part of the control system are rotatable by the centrifuge;
providing the control system with at least one pressurized fluid supply;
coupling a pressurized fluid supply line communicating between the at least one pressurized fluid supply and a port of the chip; and
operating a flow control device for selectively controlling a pressure supplied to the chip.

### Claim 37 (depends on 36)

The method of claim 36 wherein operating the flow control device comprises applying a pressure difference between a first and a second port of the chip to bubble a liquid in a reservoir, where the first port is coupled to the reservoir below a meniscus of the liquid, the second port is coupled to the reservoir above the meniscus, and the pressure applied at the second port is lower than that applied at the first port.

### Claim 38 (depends on 36)

The method of claim 36 wherein operating the flow control device comprises applying a pressure to a channel to move a liquid from a first reservoir connected with the channel to a second reservoir.

### Claim 39 (depends on 38)

The method of claim 38 wherein the second reservoir is closer to an axis of rotation of the centrifuge than the first reservoir.

### Claim 40 (depends on 38)

The method of claim 38 wherein the first reservoir is in a vial off of the chip, and the second reservoir is on the chip.

### Claim 41 (depends on 38)

The method of claim 38 wherein applying the pressure to the channel to move the liquid comprises priming a siphon valve.

### Claim 42 (depends on 38)

The method of claim 38 wherein operating the flow control device comprises operating a plurality of flow control devices in a plurality of supply lines to selectively move the liquid in one of two or more directions.

### Claim 43 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42)

A kit comprising at least one of the following:
user instructions for carrying out the method of any one of claims 36 to 42;
a chip controller according to anyone of claims 1 to 35; and
non-transitory computer readable program instructions for controlling flow control devices of a chip controller according to anyone of claims 36 to 42.

### Claim 44 (depends on 43)

The kit of claim 43 further comprising at least one of the following:
tubing for connecting a port of the microfluidic chip with the supply line;
a microfluidic chip;
a blade for a centrifuge; and
a centrifuge.
