# US 12,005,453 B2 · Particle manipulation system with multisort valve and focusing element > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,005,453 B2 - Document ID: US12005453B2 - Status: Granted - Kind: B2 - Application number: 16/933,149 - Filed: 2020-07-20 - Published: 2020-11-12 - Granted: 2024-06-11 - Earliest claimed: 2013-10-01 - Assignees: Owl biomedical, Inc. - Applicants: Owl biomedical, Inc. - Inventors: Mehran Hoonejani; John Harley - Web page: https://patentgrep.com/patent/US12005453B2 ## CPC - 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 3/502707: {characterised by the manufacture of the container or its components} - 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)} - F16K 99/0046: {using magnets} - F16K 99/0048: {using piezoelectric means} - G01N 15/1404: Handling flow, e.g. hydrodynamic focusing - G01N 15/1468: {with spatial resolution of the texture or inner structure of the particle} - G01N 15/1484: {microstructural devices} - G01N 21/6402: {Atomic fluorescence; Laser induced fluorescence} - G01N 21/6428: {Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" (in vivo A61B5/00; immunoassay G01N33/53)} - G01N 21/6486: {Measuring fluorescence of biological material, e.g. DNA, RNA, cells (G01N21/6428 takes precedence)} - B01L 2200/0652: Sorting or classification of particles or molecules - B01L 2300/0627: Sensor or part of a sensor is integrated - B01L 2300/0654: Lenses; Optical fibres - B01L 2300/0864: comprising only one inlet and multiple receiving wells, e.g. for separation, splitting - B01L 2400/0622: distribution valves, valves having multiple inlets and/or outlets, e.g. metering valves, multi-way valves - B01L 2400/0633: with moving parts - 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 2021/6439: {with indicators, stains, dyes, tags, labels, marks} - G01N 2201/06113: Coherent sources; lasers - B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE - 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)} - 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 particle manipulation system uses a MEMS-based, microfabricated particle manipulation device which has a sample inlet channel, output channels, and a movable member formed on a substrate. The device may be used to separate a target particle from non-target material in a sample stream. In order to improve the sorter speed, accuracy or yield, the particle manipulation system may also include a microfluidic structure which focuses the target particles in a particular portion of the sample inlet channel. The particle manipulation device may have two separate sort output channels, wherein the sort channel used depends on the characteristics of the sort pulse delivered to the micromechanical particle manipulation device. ## Claims ### Claim 1 A micromechanical particle manipulation device, comprising: a sample inlet channel formed in a material, and through which a fluid flows, the fluid including target particles and non-target material, wherein the flow in the sample inlet channel is substantially in a single plane, a particle focusing element coupled to the sample inlet channel, wherein the particle focusing element is configured to urge the target particles into a particular region of the sample inlet channel, wherein the focusing element comprises a first portion with a variable cross section which urges particles into at least one locus in a particular portion of the cross section, and a second portion with a substantially uniform cross section; and wherein the focusing element further comprises a bend that rotates the at least one locus to a second different portion of the cross section, and wherein the first portion, the second portion, and the bend together concentrate the target particles into a single locus within the sample inlet channel; and a microfabricated sorting device that manipulates the target particles concentrated in the particular region of the sample inlet channel, wherein the microfabricated sorting device has a first diverting surface, wherein the movable member moves from a first position to a second position in response to a force applied to the movable member, wherein the motion is substantially in another plane parallel to the surface of the substrate; a sample inlet channel formed in the substrate and through which a fluid flows, the fluid including target particles and non-target material, wherein the flow in the sample inlet channel is substantially parallel to the surface; and a plurality of output channels including a sort output channel into which the microfabricated member diverts the target particles, and a waste output channel into which the non-target material flows, and wherein the flow in waste output channel is substantially orthogonal to the plane, and wherein the waste output channel is located directly below at least a portion of the microfabricated member over at least a portion of its motion. ### Claim 2 (depends on 1) The micromechanical particle manipulation device of claim 1, wherein the bend comprises at least one of a change in aspect ratio (height/width) from less than one to greater than one. ### Claim 3 (depends on 1) The micromechanical particle manipulation device of claim 1, wherein the variable cross section portion of the particle focusing element channel defines a triangular cavity, wherein the cavity is characterized by a cavity height H, and a cavity width L, and a cavity angle. ### Claim 4 (depends on 1) The micromechanical particle manipulation device of claim 1, wherein at least a part of the variable cross section portion maintains an aspect ratio (height/width) of more than one. ### Claim 5 (depends on 1) The micromechanical particle manipulation device of claim 1, wherein at least a part of the variable cross section portion maintains an aspect ratio (height/width) of less than one, and at least another part of the variable cross section portion maintains an aspect ratio (height/width) of more than one. ### Claim 6 (depends on 1) The micromechanical particle manipulation device of claim 1, wherein the first portion of the focusing element is disposed in a first portion of material and the second portion of the particle focusing element is disposed in a second portion of material and the first portion of material is joined to the second portion of material by a glue line. ### Claim 7 (depends on 2) The micromechanical particle manipulation device of claim 2, wherein the cavities have cavity size (H/W) of about 5 to 15. ### Claim 8 (depends on 2) The micromechanical particle manipulation device of claim 2, wherein the cavities have a pitch ratio (P/H) of about 4. ### Claim 9 (depends on 3) The micromechanical particle manipulation device of claim 3, wherein the flow rate within the particle focusing element is about 8 ml/hour. ### Claim 10 (depends on 2) The micromechanical particle manipulation device of claim 2, wherein the sample inlet channels have an aspect ratio W/D of less than about 1. ### Claim 11 (depends on 3) The micromechanical particle manipulation device of claim 3, wherein the particle focusing element has at least one acute bend, defining an inner surface of the acute bend and an outer surface of the acute bend, and wherein the plurality of cavities are all disposed on the outside of the acute bend. ### Claim 12 (depends on 2) The micromechanical particle manipulation device of claim 2, wherein straight and non-parallel segments define expansion/contraction cavities which balance the Dean force and the frictional force, thereby bringing the particles to a stable two-dimensional focus within the particle focusing element. ### Claim 13 (depends on 1) The micromechanical particle manipulation device of claim 1, wherein the particle focusing element is disposed in the same plane as the movable member, and formed in the same substrate. ### Claim 14 (depends on 1) The micromechanical particle manipulation device of claim 1, wherein the sample inlet channel and particle focusing elements both have characteristic dimensions of about 50-150 microns. ### Claim 15 (depends on 1) The micromechanical particle manipulation device of claim 1, wherein the target particles are at least one of a stem cell, a cancer cell, a zygote, a protein, a T-cell, a bacteria, a component of blood, and a DNA fragment. ### Claim 16 (depends on 1) The micromechanical particle manipulation device of claim 1, further comprising: an electromagnet. ### Claim 17 (depends on 12) The micromechanical particle manipulation device of claim 12, wherein the movable member moves from the first position to the second position when the electromagnet is activated. ### Claim 18 (depends on 1) The micromechanical particle manipulation device of claim 1, further comprising: a first permeable magnetic material inlaid in the movable member; a first stationary permeable magnetic feature disposed on the substrate; and a first source of magnetic flux external to the movable member and substrate on which the movable member is formed. ### Claim 19 (depends on 1) The micromechanical particle manipulation device of claim 1, wherein the force is at least one of magnetic, electrostatic, and piezoelectric.