# US 11,027,279 B2 · Apparatus, system and method for performing automated centrifugal separation

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- Number: US 11,027,279 B2
- Document ID: US11027279B2
- Status: Granted
- Kind: B2
- Application number: 16/818,095
- Filed: 2020-03-13
- Published: 2020-07-02
- Granted: 2021-06-08
- Earliest claimed: 2014-05-16
- Assignees: Qvella Corporation
- Applicants: Qvella Corporation
- Inventors: Robert Maaskant; Sanjesh Yasotharan; Samad Talebpour; Stephen W. Leonard; Cyrus Etemad-Moghadam; Alexander Zahn
- Web page: https://patentgrep.com/patent/US11027279B2

## CPC

- B01L 3/502753: {characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation}
- B01D 17/0217: {by centrifugal force}
- B01D 19/0052: {in rotating vessels, vessels containing movable parts or in which centrifugal movement is caused (B01D19/0026 takes precedence)}
- B01D 21/262: {by using a centrifuge}
- B01L 3/5021: {Test tubes specially adapted for centrifugation purposes}
- B01L 3/502715: {characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces}
- B01L 3/502738: {characterised by integrated valves (throttle valves in microfluidic sample containers B01L3/502746)}
- B01L 7/52: {with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples}
- B04B 5/0407: {for liquids contained in receptacles (B04B5/0442 takes precedence)}
- B04B 5/0421: {pivotably mounted}
- B04B 13/00: Control arrangements specially designed for centrifuges; Program control of centrifuges (control arrangements for feed, charge or discharge B04B11/00)
- C12N 15/1003: {Extracting or separating nucleic acids from biological samples, e.g. pure separation or isolation methods; Conditions, buffers or apparatuses therefor}
- F16K 7/00: Diaphragm {valves or} cut-off apparatus, e.g. with a member deformed, but not moved bodily, to close the passage (container gates or closures operating by deformation of flexible walls B65D90/56; means for plugging pipes or hoses F16L55/10 ){; Pinch valves}
- F16K 99/0015: {Diaphragm or membrane valves}
- F16K 99/0042: {Electric operating means therefor}
- B01L 2200/027: for microfluidic devices
- B01L 2200/0684: Venting, avoiding backpressure, avoid gas bubbles
- B01L 2200/10: Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
- B01L 2300/0816: Cards, e.g. flat sample carriers usually with flow in two horizontal directions
- B01L 2300/0887: Laminated structure
- B01L 2300/1822: using Peltier elements
- B01L 2300/1827: using resistive heater
- B01L 2300/1844: using fans
- B01L 2400/0409: centrifugal forces
- B01L 2400/0487: fluid pressure, pneumatics
- B01L 2400/0655: pinch valves
- F16K 2099/0084: {Chemistry or biology, e.g. "lab-on-a-chip" technology}
- B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01D: SEPARATION (separating solids from solids by wet methods B03B, B03D; by pneumatic jigs or tables B03B; by other dry methods B07; magnetic or electrostatic separation of solid materials from solid materials or fluids, separation by high-voltage electric fields B03C; centrifuges, vortex apparatus B04; presses per se for squeezing-out liquid from liquid-containing material B30B9/02; treatment of water C02F, e.g. softening by ion-exchange C02F1/42; {arrangements of air intake cleaners in gas turbine plants F02C7/05} ; arrangements or mounting of filters in air-conditioning, air-humidification or ventilation F24F13/28)
- B04B: CENTRIFUGES (high-speed drum mills B02C19/11; domestic spin driers D06F; analysing, measuring or monitoring physical or chemical properties of samples during centrifuging, see the relevant subclasses for these procedures, e.g. G01N)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- 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)}

## Abstract

Systems, methods and devices are provided for the automated centrifugal processing of samples. In some embodiments, an integrated fluidic processing cartridge is provided, in which a centrifugation chamber is fluidically interfaced, through a lateral surface thereof, with a microfluidic device, and wherein the integrated fluidic processing cartridge is configured to be inserted into a centrifuge for centrifugation. A cartridge interfacing assembly may be employed to interface with the integrated fluidic processing cartridge for performing various fluidic processing steps, such as controlling the flow of fluids into and out of the centrifugation chamber, and controlling the flow of fluids into the microfluidic device, and optionally for the further fluidic processing of fluids extracted to the micro-fluidic device. The integrated fluidic processing cartridge may include a supernatant chamber the extraction of a supernatant thereto, and a dilutent chamber for diluting a suspension collected in the centrifugation chamber.

## Claims

### Claim 1

A system for performing centrifugal separation and fluidic processing, said system comprising:
a fluidic processing cartridge comprising a valve;
a centrifugation device comprising:
a rotor; and
a receptacle pivotally connected to said rotor, said receptacle being configured to receive said fluidic processing cartridge, said receptacle comprising a mechanical valve latching mechanism; and
a cartridge interfacing assembly capable of engaging with said receptacle and actuating said valve latching mechanism to open said valve when said rotor is at rest and said fluidic processing cartridge resides within said receptacle;
said valve latching mechanism being configured to mechanically latch said valve in a closed state when said fluidic processing cartridge resides within said receptacle and said cartridge interfacing assembly is disengaged from said receptacle.

### Claim 2 (depends on 1)

The system according to claim 1 wherein said valve and said mechanical valve latching mechanism are configured such that leakage of fluid through said valve is prevented when said valve is mechanically latched in the closed state during centrifugation despite fluidic pressures generated during centrifugation.

### Claim 3 (depends on 1)

The system according to claim 1 wherein said mechanical valve latching mechanism is configured such that during centrifugation, a centrifugal force applied to said mechanical valve latching mechanism results in a compressive force applied to said valve.

### Claim 4 (depends on 1)

The system according to claim 1 wherein said mechanical valve latching mechanism comprises a pin that is held captive in a wall of said cartridge interfacing assembly, said pin being biased against said valve when said fluidic processing cartridge resides within said receptacle and said cartridge interfacing assembly is disengaged from said receptacle, wherein said cartridge interfacing assembly is capable of retracting said pin to open said valve.

### Claim 5 (depends on 4)

The system according to claim 4 wherein said cartridge interfacing assembly comprises a gripping mechanism configured to grip said pin for retraction of said pin.

### Claim 6 (depends on 4)

The system according to claim 4 wherein said cartridge interfacing assembly comprises a lever mechanism, and wherein said cartridge interfacing assembly is capable of retracting said pin to open said valve.

### Claim 7 (depends on 6)

The system according to claim 6 wherein said lever mechanism is configured to bear against a surface of said receptacle and an underside of said pin.

### Claim 8 (depends on 6)

The system according to claim 6 wherein said cartridge interfacing assembly comprises a camshaft, said camshaft comprising a cam, wherein said camshaft is rotatable such that said cam is contacted with said lever mechanism for opening said valve.

### Claim 9 (depends on 6)

The system according to claim 6 wherein said lever mechanism comprises a lever positioned such that during centrifugation, a centrifugal force applied to said lever results in a compressive force applied to said valve.

### Claim 10 (depends on 1)

The system according to claim 1 wherein said mechanical valve latching mechanism comprises a spring-loaded assembly configured to hold said valve closed by a spring force when said fluidic processing cartridge resides within said receptacle and said cartridge interfacing assembly is disengaged from said receptacle, said cartridge interfacing assembly being capable of overcoming the spring force to open said valve.

### Claim 11 (depends on 1)

The system according to claim 1 wherein said mechanical valve latching mechanism comprises a ratchet device configured to lock said valve in the closed state when said fluidic processing cartridge resides within said receptacle and said cartridge interfacing assembly is disengaged from said receptacle, wherein said ratchet device is releasable by said cartridge interfacing assembly to open said valve.

### Claim 12 (depends on 1)

The system according to claim 1 wherein said mechanical valve latching mechanism comprises a screw that is received within a threaded aperture in said receptacle, wherein a position of an end face of the screw, relative to said receptacle, is adjustable to bring said valve into the closed state when said fluidic processing cartridge resides within said receptacle.

### Claim 13 (depends on 12)

The system according to claim 12 wherein said mechanical valve latching mechanism further comprises a contact pin mounted on said receptacle at a location intermediate to said valve and said screw, said contact pin being configured to be engaged and actuated by said screw during rotation of said screw for contacting and closing said valve.

### Claim 14 (depends on 13)

The system according to claim 13 wherein said contact pin is keyed in a manner so as to prevent rotation thereof during engagement and actuation by said screw.

### Claim 15 (depends on 1)

The system according to claim 1 wherein said valve and said mechanical valve latching mechanism are configured such that leakage of fluid through said valve is prevented when said valve is mechanically latched in the closed state during centrifugation with an applied centrifugal force between 1000 g and 15,000 g despite fluidic pressures generated during centrifugation.

### Claim 16 (depends on 1)

The system according to claim 1 wherein said valve and said mechanical valve latching mechanism are configured such that leakage of fluid through said valve is prevented when said valve is mechanically latched in the closed state during centrifugation with an applied centrifugal force between 3000 g and 10,000 g despite fluidic pressures generated during centrifugation.

### Claim 17 (depends on 1)

The system according to claim 1 wherein said valve and said mechanical valve latching mechanism are configured such that leakage of fluid through said valve is prevented when said valve is mechanically latched in the closed state during centrifugation with an applied centrifugal force between 2000 g and 12,000 g despite fluidic pressures generated during centrifugation.

### Claim 18 (depends on 1)

The system according to claim 1 wherein said valve and said mechanical valve latching mechanism are configured such that leakage of fluid through said valve is prevented when said valve is mechanically latched in the closed state during centrifugation with an applied centrifugal force between 4000 g and 8000 g despite fluidic pressures generated during centrifugation.

### Claim 19 (depends on 1)

A method of performing centrifugal processing of a fluidic processing cartridge, the fluidic processing cartridge comprising a valve, the method comprising:
providing a system according to claim 1, wherein the fluidic processing cartridge resides within said receptacle;
while the cartridge interfacing assembly is engaged with the receptacle and the centrifugation device is at rest, employing the cartridge interfacing assembly to actuate the valve latching mechanism to open the valve, thereby facilitating transport of a fluid within the fluidic processing cartridge;
disengaging the cartridge interfacing assembly from the receptacle, such that the valve is mechanically latched in the closed state by the valve latching mechanism; and
controlling the centrifugation device to centrifuge the fluidic processing cartridge while the valve latching mechanism maintains the valve in the closed state.

### Claim 20 (depends on 19)

The method according to claim 19 wherein the valve and the mechanical valve latching mechanism are configured such that leakage of the fluid through the valve is prevented when the valve is mechanically latched in the closed state during centrifugation despite fluidic pressures generated during centrifugation.

### Claim 21 (depends on 20)

The method according to claim 20 wherein the mechanical valve latching mechanism is configured such that during centrifugation, a centrifugal force applied to the mechanical valve latching mechanism results in a compressive force applied to the valve.