IP Library Granted Patent US 12,186,751
Granted Patent B2
US 12,186,751 · App. 16/915,240 · Granted Jan 7, 2025

Devices and systems incorporating acoustic ordering and methods of use thereof

Inventors: Alireza Salmanzadeh (Pleasanton, CA); Rajiv Bharadwaj (Pleasanton, CA)
Assignee: 10x Genomics, Inc.
B01L3/502761B01L2200/027B01L2200/0652B01L2400/0496
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Quick Facts
Patent No.
US 12,186,751
App. No.
16/915,240
Granted
Jan 7, 2025
Kind
B2
Abstract

Devices, systems, and their methods of use, for generating droplets are provided. One or more geometric parameters of a microfluidic channel can be selected to generate droplets of a desired and predictable droplet size.

Claims (67)

1. A device for ordering particles in a liquid, comprising:

a) a first channel having a first inlet and a first outlet; and

b) a first source of acoustic energy operatively coupled to the first channel to produce an acoustic wave having a first plurality of evenly spaced nodes disposed longitudinally in the first channel to generate evenly spaced first particles in a first liquid in the first channel in the direction of flow;

c) a first pump configured to transport the first particles in the first channel;

d) a second channel having a second inlet and a second outlet, wherein the second channel has an intersection with the first channel between the first inlet and the first outlet;

e) a second source of acoustic energy operatively coupled to the second channel to produce an acoustic wave having a second plurality of evenly spaced nodes disposed longitudinally in the second channel to generate evenly spaced second particles in a second liquid in the second channel in the direction of flow;

f) a second pump configured to transport the second particles in the second channel; and

g) a third channel, wherein the third channel has an intersection with the first channel between (i) the intersection of the second channel and (ii) the first channel outlet.

2. The device of claim 1 , further comprising

a source of first particles in fluid communication with the first inlet.

3. The device of claim 1 , wherein the first source of acoustic energy comprises an interdigitated transducer or a piezoelectric material.

4. The device of claim 1 , further comprising a source of second particles in fluid communication with the second channel.

5. The device of claim 1 , wherein the first source of acoustic energy comprises a standing acoustic wave actuator.

6. The device of claim 1 , wherein the second source of acoustic energy comprises an interdigitated transducer or a piezoelectric material.

7. The device of claim 1 :

i) wherein the device further comprises a collection region in fluid communication with the first outlet; or

ii) wherein a droplet formation region comprises the intersection of the third channel the first channel, and wherein the droplet formation region is configured to form droplets comprising a first particle from the first liquid in the first channel and a second particle from the second liquid in the second channel, wherein the droplet formation region is in fluid communication with the first outlet.

8. A method of ordering particles in a liquid, comprising:

a) providing the device of claim 1 ;

b) actuating the first source of acoustic energy of the device to propagate the acoustic wave having the first plurality of nodes in the first channel and actuating the second source of acoustic energy of the device to propagate the acoustic wave having the second plurality of nodes in the second channel;

c) allowing first particles in the first liquid in the first channel to order according to the first plurality of nodes and allowing second particles in the second liquid in the second channel to order according to the second plurality of nodes; and

d) pumping the ordered particles in the first channel with the first pump and pumping the ordered particles in the second channel with the second pump.

9. The method of claim 8 , wherein:

i) the first source of acoustic energy comprises an interdigitated transducer or a piezoelectric material; or

ii) the device further comprises a collection region in fluid communication with the first outlet.

10. The method of claim 8 , wherein the particle comprises a cell, a bead, or a combination thereof.

11. A method of producing droplets comprising a particle, comprising:

a) providing a device comprising:

i) a first channel having a first inlet and a first outlet;

ii) a first source of acoustic energy operatively coupled to the first channel;

iii) a droplet formation region in fluid communication with the first outlet;

iv) a first pump configured to transport the ordered particles in the first channel;

v) a second channel having a second inlet and a second outlet, wherein the second channel intersects the first channel between the first inlet and the first outlet;

vi) a second source of acoustic energy operatively coupled to the second channel; and

vii) a second pump configured to transport the ordered particles in the second channel;

b) actuating the first source of acoustic energy of the device to propagate an acoustic wave having a first plurality of evenly spaced nodes disposed longitudinally in the first channel and actuating the second source of acoustic energy of the device to propagate an acoustic wave having a second plurality of evenly spaced nodes disposed longitudinally in the second channel;

c) allowing first particles in a first liquid to evenly space in the first channel in the direction of flow and allowing second particles in a second liquid in the second channel to evenly space in the second channel in the direction of flow; and

d) pumping the first particles in the first channel to the droplet formation region with the first pump and pumping the second particles in the second channel with the second pump to the droplet formation region so that the droplets produced by the droplet formation region preferentially contain a specified number of particles.

12. The method of claim 11 , wherein:

i) the first source of acoustic energy comprises an interdigitated transducer or a piezoelectric material; and/or

ii) the device further comprises a collection region in fluid communication with the first outlet.

13. The method of claim 12 , wherein the first source of acoustic energy comprises a standing acoustic wave actuator that propagates an acoustic wave with one or more the first plurality of nodes in the first channel.

14. The method of claim 13 , wherein:

i) the second source of acoustic energy comprises an interdigitated transducer or a piezoelectric material; and/or

a specified number of particles in the first channel are preferentially associated with a specified number of particles in the second channel at the intersection of the first and second channels.

15. The method of claim 14 , wherein:

i) the specified number of particles in the first channel is 1;

ii) the specified number of particles in the second channel is 1; and/or

iii) the particles in the first channel and/or the second channel comprise a cell, a bead, or a combination thereof.

16. A system for ordering particles in a liquid, comprising:

a) a device comprising a first channel having a first inlet and a first outlet;

b) a first source of acoustic energy operatively coupled to the first channel to produce an acoustic wave having a first plurality of evenly spaced nodes disposed longitudinally in the first channel to generate evenly spaced first particles in a first liquid in the first channel in the direction of flow;

c) a first pump configured to transport the first particles in the first channel;

d) a second channel having a second inlet and a second outlet, wherein the second channel intersects the first channel between the first inlet and the first outlet;

e) a second source of acoustic energy operatively coupled to the second channel to produce an acoustic wave having a second plurality of evenly spaced nodes disposed longitudinally in the second channel to generate evenly spaced second particles in a second liquid in the second channel in the direction of flow;

f) a second pump configured to transport the second particles in the second channel; and

g) a third channel, wherein the third channel has an intersection with the first channel between (i) the intersection of the second channel and (ii) the first channel outlet.

17. The system of claim 16 , wherein:

i) the system further comprises a first source of first particles in fluid communication with the first inlet;

ii) the first source of acoustic energy comprises an interdigitated transducer or a piezoelectric material; and/or

iii) the device further comprises a collection region in fluid communication with the first outlet.

18. The system of claim 17 , wherein:

i) the device further comprises a source of second particles in fluid communication with the second channel.

19. The system of claim 16 , wherein:

i) the second source of acoustic energy comprises an interdigitated transducer or a piezoelectric material; and/or

ii) the particles in the second channel comprise a cell, a bead, or a combination thereof.

20. The system of claim 16 , wherein the particles in the first channel comprise a cell, a bead, or a combination thereof.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 18, 2020
From: SALMANZADEH, ALIREZA; BHARADWAJ, RAJIV
To: 10X GENOMICS, INC.
Reel/Frame 054402/0991 →
Continuity (2)
Provisional Application 62868566 · Jun 28, 2019
Related Publication 20200406261A1 · Dec 31, 2020
References Cited (160)
US 5700692A · Sweet · 1997 [cited by applicant]
US 5842787A · Kopf-Sill et al. · 1998 [cited by applicant]
US 5872010A · Karger et al. · 1999 [cited by applicant]
US 6216538B1 · Yasuda et al. · 2001 [cited by applicant]
US 6296020B1 · McNeely et al. · 2001 [cited by applicant]
US 6432290B1 · Harrison et al. · 2002 [cited by applicant]
US 6778724B2 · Wang et al. · 2004 [cited by applicant]
US 6808075B2 · Bohm et al. · 2004 [cited by applicant]
US 6877528B2 · Gilbert et al. · 2005 [cited by applicant]
US 6880576B2 · Karp et al. · 2005 [cited by applicant]
US 6994218B2 · Kawano et al. · 2006 [cited by applicant]
US 7264972B2 · Foster · 2007 [cited by applicant]
US 7452725B2 · Leary et al. · 2008 [cited by applicant]
US 7699767B2 · Mueth et al. · 2010 [cited by applicant]
US 7901947B2 · Pollack et al. · 2011 [cited by applicant]
US 7943671B2 · Herminghaus et al. · 2011 [cited by applicant]
US 8096421B2 · Shinoda · 2012 [cited by applicant]
US 8186913B2 · Toner et al. · 2012 [cited by applicant]
US 8387803B2 · Thorslund et al. · 2013 [cited by applicant]
US 8467040B2 · Luscher · 2013 [cited by applicant]
US 8524173B2 · Yamanaka et al. · 2013 [cited by applicant]
US 8529026B2 · Clarke et al. · 2013 [cited by applicant]
US 8592221B2 · Fraden et al. · 2013 [cited by applicant]
US 8741192B2 · Torii et al. · 2014 [cited by applicant]
US 8820538B1 · Lin · 2014 [cited by applicant]
US 8821006B2 · Norikane et al. · 2014 [cited by applicant]
US 8871500B2 · Foster et al. · 2014 [cited by applicant]
US 8944083B2 · Collier et al. · 2015 [cited by applicant]
US 9012390B2 · Holtze et al. · 2015 [cited by applicant]
US 9017623B2 · Fraden et al. · 2015 [cited by applicant]
US 9133009B2 · Baroud et al. · 2015 [cited by applicant]
US 9399215B2 · Cauley, III et al. · 2016 [cited by applicant]
US 9403294B2 · Cauley, III · 2016 [cited by applicant]
US 9638620B2 · Di Carlo et al. · 2017 [cited by applicant]
US 9700891B2 · Smith et al. · 2017 [cited by applicant]
US 10011872B1 · Belgrader et al. · 2018 [cited by applicant]
US 10323278B2 · Belgrader et al. · 2019 [cited by applicant]
US 20010036669A1 · Jedrzejewski et al. · 2001 [cited by applicant]
US 20030005967A1 · Karp · 2003 [cited by applicant]
US 20040108917A1 · Jian et al. · 2004 [cited by applicant]
US 20040109793A1 · McNeely et al. · 2004 [cited by applicant]
US 20070065808A1 · Bohm et al. · 2007 [cited by applicant]
US 20070166200A1 · Zhou et al. · 2007 [cited by applicant]
US 20080038810A1 · Pollack et al. · 2008 [cited by applicant]
US 20080050283A1 · Chou et al. · 2008 [cited by applicant]
US 20090090422A1 · Baroud et al. · 2009 [cited by applicant]
US 20090269824A1 · Kim et al. · 2009 [cited by applicant]
US 20100006441A1 · Renaud et al. · 2010 [cited by applicant]
US 20100018584A1 · Bransky · 2010 [cited by examiner]
US 20100021984A1 · Edd et al. · 2010 [cited by applicant]
US 20110000560A1 · Miller et al. · 2011 [cited by applicant]
US 20110086377A1 · Thwar et al. · 2011 [cited by applicant]
US 20110154890A1 · Holm et al. · 2011 [cited by applicant]
US 20110223314A1 · Zhang et al. · 2011 [cited by applicant]
US 20120091059A1 · Beer et al. · 2012 [cited by applicant]
US 20120121480A1 · Frenz et al. · 2012 [cited by applicant]
US 20120142018A1 · Jiang · 2012 [cited by applicant]
US 20120236299A1 · Chiou et al. · 2012 [cited by applicant]
US 20120315690A1 · Di Carlo et al. · 2012 [cited by applicant]
US 20130236901A1 · Potier et al. · 2013 [cited by applicant]
US 20140008307A1 · Guldiken et al. · 2014 [cited by applicant]
US 20140155295A1 · Hindson et al. · 2014 [cited by applicant]
US 20140179544A1 · Steenblock et al. · 2014 [cited by applicant]
US 20140326339A1 · Toner et al. · 2014 [cited by applicant]
US 20150034163A1 · Abate et al. · 2015 [cited by applicant]
US 20150224466A1 · Hindson et al. · 2015 [cited by applicant]
US 20150258543A1 · Baroud et al. · 2015 [cited by applicant]
US 20150267246A1 · Baroud et al. · 2015 [cited by applicant]
US 20150292988A1 · Bharadwaj · 2015 [cited by examiner]
US 20150298157A1 · Weitz · 2015 [cited by examiner]
US 20150336096A1 · Smith et al. · 2015 [cited by applicant]
US 20150360236A1 · Garcia et al. · 2015 [cited by applicant]
US 20160097087A1 · Wiyatno et al. · 2016 [cited by applicant]
US 20160250637A1 · Neild et al. · 2016 [cited by applicant]
US 20170009274A1 · Abate et al. · 2017 [cited by applicant]
US 20170114385A1 · Di Carlo et al. · 2017 [cited by applicant]
US 20170138935A1 · Rivas · 2017 [cited by applicant]
US 20170165663A1 · Hong et al. · 2017 [cited by applicant]
US 20170266653A1 · Pollack · 2017 [cited by examiner]
US 20180056294A1 · Di Carlo et al. · 2018 [cited by applicant]
US 20180193829A1 · Boitard et al. · 2018 [cited by applicant]
US 20180214874A1 · Koksal et al. · 2018 [cited by applicant]
US 20180334670A1 · Bharadwaj · 2018 [cited by examiner]
US 20190307946A1 · Fiering et al. · 2019 [cited by applicant]
US 20200290048A1 · Bharadwaj et al. · 2020 [cited by applicant]
US 20210053053A1 · Salmanzadeh et al. · 2021 [cited by applicant]
US 20210205811A1 · Salmanzadeh et al. · 2021 [cited by applicant]
WO WO2007138178A2 · 2007 [cited by applicant]
WO WO2010128858A1 · 2010 [cited by applicant]
WO WO2010151776A2 · 2010 [cited by applicant]
WO WO2013112121A1 · 2013 [cited by applicant]
WO WO2015132317A1 · 2015 [cited by applicant]
WO WO2015132318A1 · 2015 [cited by applicant]
WO WO2015160919A1 · 2015 [cited by applicant]
WO WO2015191534A2 · 2015 [cited by applicant]
WO WO2016035284A1 · 2016 [cited by applicant]
WO WO2016065056A1 · 2016 [cited by applicant]
WO WO2016075172A1 · 2016 [cited by applicant]
WO WO2016151107A1 · 2016 [cited by applicant]
WO WO2017005872A1 · 2017 [cited by applicant]
WO WO2017075549A1 · 2017 [cited by applicant]
WO WO2017083375A1 · 2017 [cited by applicant]
WO WO2017117490A1 · 2017 [cited by applicant]
WO WO2017180949A1 · 2017 [cited by applicant]
WO WO2019157529A1 · 2019 [cited by applicant]
Guldiken et al.(Sheathless Size-Based Acoustic Particle Separation, Sensors, 2102, 12, pp. 905-922 (Year: 2012). [cited by examiner]
Abate et al., “High-throughput injection with microfluidics using picoinjectors,” Proc Natl Acad Sci USA. 107(45): 19163-6 (2010). [cited by applicant]
Abate et al., “Valve based flow focusing for drop formation,” Appl Phys Lett. 94(2):023503-1-3 (2009) (3 pages). [cited by applicant]
AGC Chemicals, “Amorphous Fluoropolymer CYTOP: Chemistry for a Blue Planet,” Jul. 2015 (10 pages). [cited by applicant]
Akartuna et al., “Chemically induced coalescence in droplet-based microfluidics,” Lab Chip. DOI:10.1039/c4lc01285b (2014) (5 pages). [cited by applicant]
Attia et al., “Micro-injection moulding of polymer microfluidic devices,” Microfluid Nanofluidics. 7(1): 1-28 (2009) (30 pages). [cited by applicant]
Baret et al., “Fluorescence-activated droplet sorting (FADS): efficient microfluidic cell sorting based on enzymatic activity,” Lab Chip. 9(13): 1850-1859 (2009). [cited by applicant]
Becker et al., “Polymer microfabrication technologies for microfluidic systems,” Anal Bioanal Chem. 390(1): 89-111 (2008). [cited by applicant]
Bransky et al., “A microfluidic droplet generator based on a piezoelectric actuator,” Lab Chip. 9(4): 516-520 (2009). [cited by applicant]
Brouzes et al., “Droplet microfluidic technology for single-cell high-throughput screening,” Proc Natl Acad Sci U S A. 106(34): 14195-14200 (2009). [cited by applicant]
Brower et al., “Optimized double emulsion flow cytometry with high-throughput single droplet isolation,” bioRxiv preprint posted online Nov. 8, 2019; doi: http://dx.doi.org/10.1101/803460. [cited by applicant]
Chakraborty et al., “Microfluidic step-emulsification in axisymmetric geometry,” Lab Chip. 17(21): 3609-3620 (2017). [cited by applicant]
Chokkalingam et al., “Self-synchronizing pairwise production of monodisperse droplets by microfluidic step emulsification,” Appl Phys Lett. 93(25): 254101-1-254101-3 (2008). [cited by applicant]
Chou et al., “Disposable microdevices for DNA analysis and cell sorting,” Proc Solid-State Sensor and Actuator Workshop, Jun. 8-11, Hilton Head, SC, pp. 11-14 (1998). [cited by applicant]
Dangla et al., “Droplet microfluidics driven by gradients of confinement,” Proc Natl Acad Sci U S A. 110(3): 853-858 (2013). [cited by applicant]
Dangla et al., “The physical mechanisms of step emulsification,” J Phys D Appl Phys. 46(11):114003 (2013) (8 pages). [cited by applicant]
De Mello et al., Chip technology for micro-separation. [cited by applicant]
Demirci et al., “Single cell epitaxy by acoustic picolitre droplets,” Lab Chip. 7(9): 1139-1145 (2007). [cited by applicant]
Doerr, “The smallest bioreactor,” Nat Methods. 2(5): 326 (2005). [cited by applicant]
Draper et al., “Compartmentalization of electrophoretically separated analytes in a multiphase microfluidic platform,” Anal Chem. 84(13): 5801-5808 (2012). [cited by applicant]
Eggersdorfer et al., “Supplementary Information: Tandem emulsification for high-throughput production of double emulsions,” Lab Chip. 17(5):936-942 (2017) (2 pages). [cited by applicant]
Eggersdorfer et al., “Tandem emulsification for high-throughput production of double emulsions,” Lab Chip. 17(5): 936-942 (2017). [cited by applicant]
Fredrickson et al., “Macro-to-micro interfaces for microfluidic devices,” Lab Chip. 4(6): 526-533 (2004). [cited by applicant]
Galambos et al., “Precision alignment packaging for microsystems with multiple fluid connections,” Proceedings of 2001 ASME: International Mechanical Engineering Conference and Exposition, Nov. 11-16, New York, NY. pp. … [cited by applicant]
Garstecki et al., “Formation of monodisperse bubbles in a microfluidic flow-focusing device,” Appl Phys Lett. 85(13): 2649-2651 (2004). [cited by applicant]
Hati et al., “Production of monodisperse drops from viscous fluids,” Lab Chip. DOI: 10.1039/c7lc01322a (2018) (7 pages). [cited by applicant]
He et al., “Selective encapsulation of single cells and subcellular organelles into picoliter- and femtoliter-volume droplets,” Anal Chem. 77(6): 1539-1544 (2005). [cited by applicant]
Huang et al., “Coating of poly(dimethylsiloxane) with n-dodecyl-Beta-D-maltoside to minimize nonspecific protein adsorption,” Lab Chip. 5(10):1005-1007 (2005). [cited by applicant]
Huang et al., “Collective generation of milliemulsions by step-emulsification,” RSC Adv. 7(24): 14932-14938 (2017). [cited by applicant]
Hwang et al., “Surface modification of cyclic olefin copolymer substrate by oxygen plasma treatment,” Surf Coat Tech. 202(15): 3669-3674 (2008). [cited by applicant]
Kahkeshani et al., “Drop formation using ferrofluids driven magnetically in a step emulsification device,” Lab Chip. 16(13): 2474-2480 (2016). [cited by applicant]
Kawai et al., Mass-production system of nearly monodisperse diameter gel particles using droplets formation in a microchannel. [cited by applicant]
Kobayashi et al., “Effect of slot aspect ratio on droplet formation from silicon straight-through microchannels,” J Colloid Interface Sci. 279(1):277-80 (2004). [cited by applicant]
Kobayashi et al., “Preparation characteristics of oil-in-water emulsions using differently charged surfactants in straight-through microchannel emulsification,” Colloids Surf A Physicochem Eng Asp. 229(1-3): 33-41 (2003… [cited by applicant]
Li et al., “Step-emulsification in a microfluidic device,” Lab Chip. 15(4):1023-31 (2015). [cited by applicant]
Luo et al., “Microfluidic Single-Cell Manipulation and Analysis: Methods and Applications,” Micromachines (Basel). 10(2):104 (2019) (31 pages). [cited by applicant]
Maan et al., “Microfluidic emulsification in food processing,” J Food Eng. 147:1-7 (2015). [cited by applicant]
Mittal et al., “Dynamics of step-emulsification: From a single to a collection of emulsion droplet generators,” Phys Fluids. 26: 082109-1-082109-14 (2014). [cited by applicant]
Sahin et al., “Microfluidic EDGE emulsification: the importance of interface interactions on droplet formation and pressure stability,” Sci Rep. 6(26407):1-7 (2016). [cited by applicant]
Barea et al., “Recent Advances in Droplet-based Microfluidic Technologies for Biochemistry and Molecular Biology,” Micromachines (Basel). 10(6):412 (2019) (25 pages). [cited by applicant]
Schuler et al., “Digital droplet PCR on disk,” Lab Chip. 16 (1): 208-216 (2016). [cited by applicant]
Shaikh et al., “A modular microfluidic architecture for integrated biochemical analysis,” Proc Natl Acad Sci U S A. 102(28):9745-50 (2005). [cited by applicant]
Shim et al., “Supporting Information: Control and measurement of the phase behavior of aqueous solutions using microfluidics,” S1-S13 (2007) (13 pages). [cited by applicant]
Stolovicki et al., “Throughput enhancement of parallel step emulsifier devices by shear-free and efficient nozzle clearance,” Lab Chip. DOI: 10.1039/c7lc01037k (2017) (7 pages). [cited by applicant]
Su et al., “Microfluidics-based biochips: technology issues, implementation platforms, and design- automation challenges,” IEEE Transactions on Computer-Aided Design of Integrated Circuits and Systems. 25(2):211-23 (200… [cited by applicant]
Van Dijke et al., “EDGE emulsification for food-grade dispersions,” J Food Eng. 97(3): 348-354 (2010). [cited by applicant]
Van Dijke et al., “Effect of viscosities of dispersed and continuous phases in microchannel oil-in-water emulsification,” Microfluid Nanofluid. 9(1):77-85 (2010). [cited by applicant]
Van Dijke et al., “Microchannel Emulsification: From Computational Fluid Dynamics to Predictive Analytical Model,” Langmuir. 24(18): 10107-10115 (2008). [cited by applicant]
Van Dijke et al., “Parallelized edge-based droplet generation (EDGE) devices,” Lab Chip. 9(19): 2824-2830 (2009). [cited by applicant]
Van Dijke et al., “Simultaneous Formation of Many Droplets in a Single Microfluidic Droplet Formation Unit,” AlChE J. 56(3): 833-836 (2010). [cited by applicant]
Van Dijke et al., “The mechanism of droplet formation in microfluidic EDGE systems,” Soft Matter. 6(2): 321-330 (2010). [cited by applicant]
Xia et al., “Soft Lithography,” Angew Chem Int Ed Engl. 37:(5)551-575 (1998) (26 pages). [cited by applicant]
Zeng et al., “High-performance single cell genetic analysis using microfluidic emulsion generator arrays,” Anal Chem. 82(8):3183-90 (2010). [cited by applicant]
Wu et al., “Actuating and detecting of microdroplet using slanted finger interdigital transducers,” J Appl Phys. 98(2):024903 (2005) (7 pages). [cited by applicant]
Wang et al., “Microfluidic approach for encapsulation via double emulsions,” Current Opinion in Pharmacology. 18:35-41 (Oct. 2014). [cited by applicant]