# US 11,440,004 B2 · Microparticle sorting microchip and microparticle sorting apparatus

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- Number: US 11,440,004 B2
- Document ID: US11440004B2
- Status: Granted
- Kind: B2
- Application number: 16/762,295
- Filed: 2018-11-09
- Published: 2021-06-10
- Granted: 2022-09-13
- Earliest claimed: 2017-11-14
- Assignees: Sony Corporation
- Applicants: Sony Corporation
- Inventors: Tatsumi Ito; Kazuya Takahashi; Masahiro Matsumoto
- Web page: https://patentgrep.com/patent/US11440004B2

## CPC

- B01L 3/502715: {characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces}
- B01L 3/50273: {characterised by the means or forces applied to move the fluids}
- 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 3/502776: {specially adapted for focusing or laminating flows}
- G01N 15/1459: {the analysis being performed on a sample stream}
- G01N 15/1484: {microstructural devices}
- B01L 2200/0636: Focussing flows, e.g. to laminate flows
- B01L 2200/0652: Sorting or classification of particles or molecules
- B01L 2200/0668: Trapping microscopic beads
- B01L 2300/0627: Sensor or part of a sensor is integrated
- B01L 2300/0816: Cards, e.g. flat sample carriers usually with flow in two horizontal directions
- B01L 2300/0864: comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
- B01L 2300/14: Means for pressure control
- B01L 2400/0439: ultrasonic vibrations, vibrating piezo elements
- B01L 2400/0487: fluid pressure, pneumatics
- G01N 15/149: specially adapted for sorting particles, e.g. by their size or optical properties
- G01N 2015/0053: {in liquids, e.g. trouble}
- G01N 2015/1006: {for cytology}
- B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- 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)

## Abstract

A microparticle sorting microchip for a flow cytometer is provided to enable sorting of microparticles at higher speed, higher purity, and higher acquisition rate. The microparticle sorting microchip includes a main channel through which a microparticle-containing fluid flows, a trap channel coaxially communicating with the main channel, a trap chamber communicating with the trap channel, and a gate channel intersecting the trap channel. The trap channel has an opening intersecting the gate channel. The trap channel has a smaller cross-sectional area upstream of the opening than downstream of the opening along a direction in which the microparticle-containing fluid flows.

## Claims

### Claim 1

A microparticle sorting microchip comprising:
a main channel through which a microparticle-containing fluid flows;
a trap channel and a waste channel which each communicate with the main channel at a branch point, the trap channel coaxially communicating with the main channel;
a trap chamber communicating with the trap channel; and
a gate channel intersecting the trap channel, wherein the trap channel has an opening portion intersecting the gate channel, and
a cross-sectional area of the trap channel upstream of the opening portion is smaller than a cross-sectional area of the trap channel downstream of the opening portion, along a direction in which the microparticle-containing fluid flows.

### Claim 2 (depends on 1)

The microparticle sorting microchip of claim 1, wherein
the gate channel includes plural gate channels, and the plural gate channels are connected to an upstream end of the downstream-stage trap channel so that the plural gate channels are symmetrical to each other with respect to a center of a flow of the microparticle-containing fluid from an opening at a downstream end of the upstream-stage trap channel.

### Claim 3 (depends on 1)

The microparticle sorting microchip of claim 1, wherein
the gate channel is configured to allow a gate flow fluid to always flow at a constant flow rate.

### Claim 4 (depends on 3)

The microparticle sorting microchip of claim 3, wherein in the downstream-stage trap channel, the gate flow fluid is branched to flow from the gate channel in a direction toward the upstream-stage trap channel and in a direction toward a pressure chamber.

### Claim 5 (depends on 1)

The microparticle sorting microchip of claim 1, wherein
the trap chamber includes a pressure chamber.

### Claim 6 (depends on 5)

The microparticle sorting microchip of claim 5, wherein
the pressure chamber has a vibration plate.

### Claim 7 (depends on 5)

The microparticle sorting microchip of claim 5, wherein
the pressure chamber is repeatedly controlled in internal pressure to a negative pressure, a positive pressure, and a normal pressure.

### Claim 8 (depends on 1)

The microparticle sorting microchip of claim 1, wherein
the main channel includes a microparticle detection region.

### Claim 9 (depends on 1)

The microparticle sorting microchip of claim 1, further comprising:
a connection channel between the trap channel and the trap chamber.

### Claim 10 (depends on 1)

The microparticle sorting microchip of claim 1, wherein
the main channel is connected with a microparticle-containing fluid inlet through which the microparticle-containing fluid is introduced.

### Claim 11 (depends on 1)

The microparticle sorting microchip of claim 1, wherein
the main channel is connected with a sheath fluid inlet through which the sheath fluid is introduced.

### Claim 12 (depends on 1)

The microparticle sorting microchip of claim 1, wherein
the main channel is connected with a branch channel which branches upstream of the trap channel and through which a portion of a fluid which has not flowed into the trap channel is allowed to flow.

### Claim 13 (depends on 11)

The microparticle sorting microchip of claim 11, wherein
the branch channel is connected with a sheath fluid container and/or a gate fluid container channel.

### Claim 14 (depends on 1)

The microparticle sorting microchip of claim 1, further comprising
downstream of the trap chamber, a microparticle collecting portion for collecting trapped microparticles.

### Claim 15 (depends on 5)

The microparticle sorting microchip of claim 5, wherein
when a microparticle has reached an upstream end of the upstream-stage trap channel, the pressure chamber is changed in internal pressure from a normal pressure to a negative pressure, and the microparticle-containing fluid is drawn into the upstream-stage trap channel and is ejected from an opening at a downstream end of the upstream-stage trap channel into the downstream-stage trap channel to cause a jet, and
after the microparticle has passed through the downstream-stage trap channel and has reached the pressure chamber, the pressure chamber is changed in internal pressure from the negative pressure or the normal pressure to a positive pressure.

### Claim 16 (depends on 15)

The microparticle sorting microchip of claim 15, wherein
the microparticle-containing fluid is ejected from the opening at the downstream end of the upstream-stage trap channel into the downstream-stage trap channel in a volume that is at least a half of a volume of the upstream-stage trap channel.

### Claim 17 (depends on 15)

The microparticle sorting microchip of claim 15, wherein
when the pressure chamber has been changed in internal pressure from the normal pressure to the negative pressure, the microparticle-containing fluid is ejected from the opening at the downstream end of the upstream-stage trap channel into the downstream-stage trap channel in a volume that is not greater than a volume in which a gate flow fluid flows from the gate channel into the downstream-stage trap channel.

### Claim 18 (depends on 15)

The microparticle sorting microchip of claim 15, wherein
when the pressure chamber has been changed in internal pressure from the normal pressure to the negative pressure, the microparticle-containing fluid is ejected from the downstream-stage trap channel in a direction toward the pressure chamber in a volume that is not greater than a volume of the downstream-stage trap channel.

### Claim 19 (depends on 1)

A microparticle sorting apparatus comprising:
a microchip mounting portion configured to mount thereon a microparticle sorting microchip according to claim 1;
a light application section that applies light onto a microparticle detection region included in the main channel;
a detection section that detects scattered light and/or fluorescence emitted from the microparticle; and
a pressure chamber control section configured to change an internal pressure of a pressure chamber as the trap chamber to a negative pressure or a positive pressure, wherein the trap chamber includes the pressure chamber.

### Claim 20 (depends on 19)

The microparticle sorting apparatus of claim 19, wherein
the pressure chamber control section has a piezo element.

### Claim 21 (depends on 19)

The microparticle sorting apparatus of claim 19, wherein
the detection section comprises one or more spots.

### Claim 22 (depends on 19)

The microparticle sorting apparatus of claim 19, wherein
the light application section comprises one or more lasers.

### Claim 23 (depends on 1)

The microparticle sorting microchip of claim 1, wherein
the gate channel is formed in a direction vertical to a plane of a main channel.

### Claim 24 (depends on 1)

The microparticle sorting microchip of claim 1, wherein
a fluid to flow through the gate channel is selected from at least one of a fluid medium used in the microparticle-containing fluid, a sheath fluid, or in a case where the microparticles are a protein, a surfactant-containing, pH-adjusted buffer solution, or a cell culture solution, or a cell storage solution, or blocking agents including solutions containing one or more proteins such as albumin, solutions containing one or more amino acids such as glycine, or solutions containing one or more nonionic surfactants such as Pluronic F68, or a solution having cytolytic activity.

### Claim 25 (depends on 1)

The microparticle sorting microchip of claim 1, wherein a length of the trap channel is at least three times a diameter of the trap channel.

### Claim 26 (depends on 1)

The microparticle sorting microchip of claim 1, wherein the gate channel includes a plurality of gate channels.

### Claim 27 (depends on 26)

The microparticle sorting microchip of claim 26, wherein the gate channels of the plurality of gate channels are disposed symmetrically with respect to a center of the trap channel.

### Claim 28 (depends on 1)

The microparticle sorting microchip of claim 1, wherein the gate channel includes an even number of gate channels disposed symmetrically with respect to a center of the trap channel.

### Claim 29 (depends on 1)

The microparticle sorting microchip of claim 1, wherein the trap channel is tapered beginning downstream of the gate channel.

### Claim 30 (depends on 1)

The microparticle sorting microchip of claim 1, wherein the trap channel includes a first stage trap channel and a second stage trap channel and wherein the second stage trap channel is tapered beginning from an upstream end of a second stage trap channel.

### Claim 31 (depends on 1)

The microparticle sorting microchip of claim 1, wherein the trap channel includes a first stage trap channel and a second stage trap channel and wherein the first stage trap channel is tapered.

### Claim 32 (depends on 1)

The microparticle sorting microchip of claim 1, wherein the trap channel includes a first stage trap channel and a second stage trap channel and wherein the first stage trap channel and the second stage trap channel are both tapered.

### Claim 33 (depends on 32)

The microparticle sorting microchip of claim 32, wherein the second stage trap channel has a greater minimum cross-sectional area than the first stage trap channel.

### Claim 34 (depends on 1)

The microparticle sorting microchip of claim 1, wherein the trap channel includes three or more stages.

### Claim 35 (depends on 34)

The microparticle sorting microchip of claim 34, wherein a gate channel intersects each of an upstream end of a second stage trap channel and an upstream end of a third stage trap channel.

### Claim 36 (depends on 34)

The microparticle sorting microchip of claim 34, wherein a gate channel intersects an upstream end of a second stage trap channel and no gate channel is connected to a third stage trap channel.

### Claim 37 (depends on 34)

The microparticle sorting microchip of claim 34, wherein a second stage trap channel and a third stage trap channel are tapered, a gate channel intersects an upstream end of the second stage trap channel, and no gate channel is connected to the third stage trap channel.
