IP Library Granted Patent US 12,427,521
Granted Patent B2
US 12,427,521 · App. 18/595,920 · Granted Sep 30, 2025

Sorting particles in a microfluidic device

Inventors: Ravi Kapur (Sharon, MA); Kyle C. Smith (Cambridge, MA); Mehmet Toner (Charlestown, MA)
Assignee: The General Hospital Corporation
B01L3/502761A61K35/28B01L3/502715B01L3/502746B01L3/502753G01N1/4077G01N15/0255G01N15/0618G01N15/1484B01L3/502776B01L2200/0631B01L2200/0647B01L2200/0652B01L2200/0668B01L2200/0684B01L2200/12B01L2300/0681B01L2300/0877B01L2300/185B01L2400/0409B01L2400/0415B01L2400/043B01L2400/0436B01L2400/0457B01L2400/0487B01L2400/082G01N2001/4088G01N2015/0053G01N15/01G01N2015/0288G01N2015/1486G01N15/149G01N2015/1493
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,427,521
App. No.
18/595,920
Granted
Sep 30, 2025
Kind
B2
Abstract

A microfluidic device includes a particle sorting region having a first, second and third microfluidic channels, a first array of islands separating the first microfluidic channel from the second microfluidic channel, and a second array of islands separating the first microfluidic channel from the third microfluidic channel, in which the island arrays and the microfluidic channels are arranged so that a first fluid is extracted from the first microfluidic channel into the second microfluidic channel and a second fluid is extracted from the third microfluidic channel into the first microfluidic channel, and so that particles are transferred from the first fluid sample into the second fluid sample within the first microfluidic channel.

Claims (10)

1. A microfluidic device comprising:

a module comprising an array of islands in a microfluidic channel, a buffer inlet in fluid communication with a first end of the microfluidic channel, and a product inlet in fluid communication with a first product outlet and a first end of the microfluidic channel, wherein:

the array of islands is arranged in one or more rows that extend along a longitudinal direction in a corresponding microfluidic channel,

each island in a row is spaced apart from an adjacent island in the row to form a siphoning channel, and

the array of islands is configured and arranged to shift portions of fluid through the siphoning channel between adjacent islands within a row to a waste outlet, and to shift particles above a specific size into a buffer flowing in the microfluidic channel and to a second product outlet.

2. The microfluidic device of claim 1 , wherein the arrays of islands include four arrays of islands.

3. The microfluidic device of claim 2 , wherein the four arrays of islands are each arranged in parallel such that a different portion of a sample fluid introduced into the microfluidic device flows through each of the four arrays of islands.

4. The microfluidic device of claim 1 , wherein each island included in the array of islands has a width between 150 and 250 micrometers, a length between 200 and 800 micrometers, and a height between 100 and 200 micrometers.

5. The microfluidic device of claim 1 , wherein each island included in the array of islands has a length-to-width ratio greater than 1.25.

6. The microfluidic device of claim 1 , wherein the siphoning channels formed in the array of islands have a respective channel width of 50 micrometers.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 11, 2024
From: SMITH, KYLE C.; KAPUR, RAVI; TONER, MEHMET
To: THE GENERAL HOSPITAL CORPORATION
Reel/Frame 066711/0465 →
Continuity (7)
Continuation 17245770 · Apr 30, 2021
Continuation 16112259 · Aug 24, 2018
Continuation 15891579 · Feb 8, 2018
Division 14931223 · Nov 3, 2015
Provisional Application 62074213 · Nov 3, 2014
Provisional Application 62074315 · Nov 3, 2014
Related Publication 20240198338A1 · Jun 20, 2024
References Cited (142)
US 5968820A · Zborowski et al. · 1999 [cited by applicant]
US 6540896B1 · Manz et al. · 2003 [cited by applicant]
US 6632652B1 · Austin et al. · 2003 [cited by applicant]
US 6767706B2 · Quake et al. · 2004 [cited by applicant]
US 7560267B2 · Yang et al. · 2009 [cited by applicant]
US 7641865B2 · Tonkovich et al. · 2010 [cited by applicant]
US 7837040B2 · Ward et al. · 2010 [cited by applicant]
US 8021614B2 · Huang et al. · 2011 [cited by applicant]
US 8186913B2 · Toner et al. · 2012 [cited by applicant]
US 8906322B2 · Huang et al. · 2014 [cited by applicant]
US 9895694B2 · Kapur et al. · 2018 [cited by applicant]
US 10150116B2 · Kapur et al. · 2018 [cited by applicant]
US 10875021B2 · Kapur et al. · 2020 [cited by applicant]
US 11027280B2 · Kapur et al. · 2021 [cited by applicant]
US 11052393B2 · Kapur et al. · 2021 [cited by applicant]
US 11944971B2 · Kapur · 2024 [cited by examiner]
US 20020187503A1 · Harrold et al. · 2002 [cited by applicant]
US 20030092029A1 · Josephson et al. · 2003 [cited by applicant]
US 20030124194A1 · Gaw et al. · 2003 [cited by applicant]
US 20030175944A1 · Yang et al. · 2003 [cited by applicant]
US 20030226806A1 · Young et al. · 2003 [cited by applicant]
US 20040033515A1 · Cao et al. · 2004 [cited by applicant]
US 20040053403A1 · Jedrzejewski et al. · 2004 [cited by applicant]
US 20040126890A1 · Gjerde et al. · 2004 [cited by applicant]
US 20040144651A1 · Huang et al. · 2004 [cited by applicant]
US 20050109716A1 · Leach et al. · 2005 [cited by applicant]
US 20060068490A1 · Tang et al. · 2006 [cited by applicant]
US 20060078888A1 · Griffiths et al. · 2006 [cited by applicant]
US 20060160243A1 · Tang et al. · 2006 [cited by applicant]
US 20060269965A1 · Josephson et al. · 2006 [cited by applicant]
US 20070026381A1 · Huang et al. · 2007 [cited by applicant]
US 20070026419A1 · Fuchs et al. · 2007 [cited by applicant]
US 20070059781A1 · Kapur et al. · 2007 [cited by applicant]
US 20070099207A1 · Fuchs et al. · 2007 [cited by applicant]
US 20070196820A1 · Kapur et al. · 2007 [cited by applicant]
US 20080023399A1 · Inglis et al. · 2008 [cited by applicant]
US 20090032449A1 · Mueth et al. · 2009 [cited by applicant]
US 20090269767A1 · Soderlund et al. · 2009 [cited by applicant]
US 20100006479A1 · Reichenbach · 2010 [cited by applicant]
US 20100059414A1 · Sturm et al. · 2010 [cited by applicant]
US 20110091987A1 · Weissleder et al. · 2011 [cited by applicant]
US 20120037544A1 · Lane et al. · 2012 [cited by applicant]
US 20120258459A1 · Huang · 2012 [cited by applicant]
US 20130079251A1 · Boles · 2013 [cited by applicant]
US 20130086980A1 · Gadini et al. · 2013 [cited by applicant]
US 20130121895A1 · Tang et al. · 2013 [cited by applicant]
US 20130168298A1 · Huang et al. · 2013 [cited by applicant]
US 20130228530A1 · Di Carlo et al. · 2013 [cited by applicant]
US 20140030788A1 · Chen et al. · 2014 [cited by applicant]
US 20140093867A1 · Burke et al. · 2014 [cited by applicant]
US 20140227777A1 · Choi et al. · 2014 [cited by applicant]
US 20140248621A1 · Collins · 2014 [cited by applicant]
US 20140342375A1 · Grisham et al. · 2014 [cited by applicant]
US 20150202356A1 · Gifford · 2015 [cited by applicant]
US 20150202549A1 · Gifford et al. · 2015 [cited by applicant]
US 20160047735A1 · Grisham et al. · 2016 [cited by applicant]
US 20160139012A1 · D'Silva et al. · 2016 [cited by applicant]
US 20160363523A1 · Reichenbach · 2016 [cited by applicant]
US 20170209864A1 · Grisham et al. · 2017 [cited by applicant]
US 20170225166A1 · Toner et al. · 2017 [cited by applicant]
US 20170254774A1 · Sabin et al. · 2017 [cited by applicant]
US 20200139370A1 · Kapur et al. · 2020 [cited by applicant]
US 20200353470A1 · Hoonejani et al. · 2020 [cited by applicant]
US 20210283610A1 · Kapur et al. · 2021 [cited by applicant]
CN 101678356 · 2010 [cited by applicant]
CN 101765762A · 2010 [cited by applicant]
CN 102791616A · 2012 [cited by applicant]
JP 2004170396 · 2004 [cited by applicant]
JP 2007196219 · 2007 [cited by applicant]
JP 2013515599 · 2013 [cited by applicant]
WO WO2000061191 · 2000 [cited by applicant]
WO WO2004037374 · 2004 [cited by applicant]
WO WO2004074814 · 2004 [cited by applicant]
WO WO2005086703 · 2005 [cited by applicant]
WO WO2006108087 · 2006 [cited by applicant]
WO WO2010123594 · 2010 [cited by applicant]
WO WO2011132164 · 2011 [cited by applicant]
WO WO2012067985 · 2012 [cited by applicant]
WO WO2014004577 · 2014 [cited by applicant]
WO WO2014107240 · 2014 [cited by applicant]
WO WO2015116990 · 2015 [cited by applicant]
Augustsson et al., “Microfluidic, Label-Free Enrichment of Prostate Cancer Cells in Blood Based on Acoustophoresis,” Anal. Chem., 84(18):7954-7965, Sep. 2012. [cited by applicant]
Burke et al., “High-throughput particle separation and concentration using spiral inertial filtration,” Biomicrofluidics 8, 024105 (2014), 18 pages. [cited by applicant]
CN Office Action in Chinese Appln. No. 201580069630.7 dated Mar. 19, 2020, 18 pages (with English translation). [cited by applicant]
CN Office Action in Chinese Appln. No. 201580069630.7, dated Apr. 2, 2019, 23 pages (with English translation). [cited by applicant]
CN Office Action in Chinese Appln. No. 201580071263.4, dated Apr. 2, 2019, 34 pages (with English translation). [cited by applicant]
CN Office Action in Chinese Appln. No. 201580071263.4, dated Mar. 9, 2020, 8 pages (with English translation). [cited by applicant]
CN Office Action in Chinese Appln. No. 201580071415.0, dated Apr. 2, 2019, 26 pages (with English translation). [cited by applicant]
CN Office Action in Chinese Appln. No. 201580071415.0, dated Mar. 19, 2020, 16 pages (with English translation). [cited by applicant]
D'Avino et al., “Single line particle focusing induced by viscoelasticity of the suspending liquid: theory, experiments and simulations to design a micropipe flow-focuser,” Lab Chip, 12(9):1638-1645, Feb. 2012. [cited by applicant]
Del Giudice et al., “Particle alignment in a viscoelastic liquid flowing in a square-shaped microchannel,” Lab Chip, 2013, 13, pp. 4263-4271, Aug. 2013. [cited by applicant]
Di Carlo et al., “Continuous inertial focusing, ordering, and separation of particles in microchannels,” Proc. Natl. Acad. Sci. U.S.A., 104(48):18892-18897, Nov. 2007. [cited by applicant]
Di Carlo et al., “Particle segregation and dynamics in confined flows,” Phys. Rev. Lett., 102(9):094503, Mar. 2009. [cited by applicant]
Di Carlo, “Inertial microfluidics,” Lab Chip, 9(21):3038-3046, Aug. 2009. [cited by applicant]
EP Extended European Search Report in European Appln. No. 15856423.7, dated Apr. 20, 2018, 8 pages. [cited by applicant]
EP Extended European Search Report in European Appln. No. 15856708.1, dated May 16, 2018, 9 pages. [cited by applicant]
EP Extended European Search Report in European Appln. No. 15856773.5, dated Apr. 20, 2018, 9 pages. [cited by applicant]
EP Extended European Search Report in European Appln. No. 20176266, dated Aug. 28, 2020, 11 pages. [cited by applicant]
EP Extended European Search Report in European Appln. No. 21152033.3, dated Jul. 8, 2021, 8 pages. [cited by applicant]
EP Office Action in European Appln. No. 15,856,773, dated Jun. 24, 2020, 4 pages. [cited by applicant]
EP Office Action in European Appln. No. 15856708.1, dated Dec. 3, 2019, 6 pages. [cited by applicant]
EP Office Action in European Appln. No. 15856773.5, dated Dec. 2, 2019, 6 pages. [cited by applicant]
Gifford et al., “Controlled Incremental Filtration: A simplified approach to design and fabrication of high-throughput microfluidic devices for selective enrichment of particles,” Lab Chip, DOI: 10.1039/C4LC00785A, Sep.… [cited by applicant]
IN Office Action in Indian Appln. No. 201737016632, dated Mar. 2, 2020, 8 pages. [cited by applicant]
IN Office Action in Indian Appln. No. 201737018681, dated Aug. 29, 2020, 8 pages. [cited by applicant]
IN Office Action in Indian Appln. No. 201737018682, dated May 22, 2019, 6 pages. [cited by applicant]
Inglis, “Efficient Microfluidic Particle Separation Arrays,” American Institute of Physics, Jan. 9, 2009, 013510-1 to 013510-3. [cited by applicant]
JP Office Action in Japanese Appln. No. 2017-523989, dated Jan. 7, 2020, 9 pages (with English translation). [cited by applicant]
JP Office Action in Japanese Appln. No. 2017-523990, dated Dec. 18, 2018, 10 pages (with English translation). [cited by applicant]
JP Office Action in Japanese Appln. No. 2017-523990, dated Jun. 7, 2019, 7 pages (with English translation). [cited by applicant]
JP Office Action in Japanese Appln. No. 2020-005143, dated Apr. 6, 2021, 11 pages (with English translation). [cited by applicant]
Kang et al., “DNA-based highly tunable particle focuser,” Nature Communications, 4:2567, Oct. 2013, 8 pages. [cited by applicant]
Lee et al., “Dynamic self-assembly and control of microfluidic particle crystals,” Proceedings of the National Academy of Sciences, 107(52):22413-22418, Nov. 2010. [cited by applicant]
Lee et al., “Multiplex Particle Focusing via Hydrodynamic Force in Viscoelastic Fluids,” Scientific Reports, 3:3258, Nov. 2013, 8 pages. [cited by applicant]
Lim et al., “Inertio-elastic focusing of bioparticles in microchannels at high throughput,” Nature Communications, (5:4120), pp. 1-9, Jun. 2014. [cited by applicant]
Loutherback, “Microfluidic Devised for High Throughput Cell Sorting and Chemical Treatment,” Dissertation, Nov. 2011. [cited by applicant]
Lubbersen et al., “High throughput particle separation with a mirrored deterministic ratchet design”, Chemical Engineering and Processing 77 (2014) 42-49. [cited by applicant]
Lubbersen et al., “Visualization of inertial flow in deterministic ratchets”, Separation and Purification Technology 109 (2013) 33-39. [cited by applicant]
Martel and Toner, “Inertial Focusing in Microfluidics,” Annual Review of Biomedical Engineering, 16:371-396, Jul. 2014. [cited by applicant]
Martel and Toner, “Particle Focusing in Curved Microfluidic Channels,” Scientific Reports, 3(3340):1-8, Nov. 2013. [cited by applicant]
Notice of Allowance in Japanese Appln. No. 2020-005143, dated Dec. 28, 2021, 5 pages (with English translation). [cited by applicant]
Office Action in Canadian Appln. No. 2,966,603, dated Nov. 5, 2021, 3 pages. [cited by applicant]
Office Action in Canadian Appln. No. 2,966,611, dated Feb. 22, 2023, 3 pages. [cited by applicant]
Office Action in Canadian Appln. No. 2,966,611, dated Nov. 5, 2021, 3 pages. [cited by applicant]
Office Action in Canadian Appln. No. 2,966,611, dated Sep. 8, 2022, 3 pages. [cited by applicant]
Office Action in Canadian Appln. No. 2,966,623, dated Feb. 21, 2023, 3 pages. [cited by applicant]
Office Action in Canadian Appln. No. 2,966,623, dated Nov. 12, 2021, 3 pages. [cited by applicant]
Office Action in Canadian Appln. No. 2,966,623, dated Sep. 9, 2022, 5 pages. [cited by applicant]
Office Action in U.S. Appl. No. 14/931,223, dated May 19, 2017, 15 pages. [cited by applicant]
Office Action in U.S. Appl. No. 14/931,421, dated May 19, 2017, 19 pages. [cited by applicant]
Office Action in U.S. Appl. No. 14/931,421, dated Oct. 4, 2017, 15 pages. [cited by applicant]
PCT International Preliminary Report on Patentability in International Appln. No. PCT/US2015/058785, dated May 9, 2017, 6 pages. [cited by applicant]
PCT International Preliminary Report on Patentability in International Appln. No. PCT/US2015/058834, dated May 9, 2017, 10 pages. [cited by applicant]
PCT International Preliminary Report on Patentability in International Appln. No. PCT/US2015/058841, dated May 9, 2017, 16 pages. [cited by applicant]
PCT International Search Report and Written Opinion in International Appln. No. PCT/US2015/058785, dated Feb. 16, 2016, 10 pages. [cited by applicant]
PCT International Search Report and Written Opinion in International Appln. No. PCT/US2015/058834, dated Feb. 17, 2016, 13 pages. [cited by applicant]
PCT International Search Report in International Appln. No. PCT/US2015/058841, dated Feb. 23, 2016, 5 pages. [cited by applicant]
PCT Written Opinion in International Appln. No. PCT/US2015/058841, dated Feb. 23, 2016, 14 pages. [cited by applicant]
Peterson et al., “Bacterial Cell Surface Damage Due to Centrifugal Compaction,” Applied and Environmental Microbiology, 78(1):120-125, Jan. 2012. [cited by applicant]
Shen et al., “High-throughput rare cell separation from blood samples using steric hindrance and inertial microfluidics,” Lab Chip, 2014, DOI: 10.1039/C3LC51384J, Mar. 2014, 15 pages. [cited by applicant]
Tanyeri et al., “A microfluidic-based hydrodynamic trap: Design and implementation,” Lab Chip, 11(10):1786-1794, May 2011. [cited by applicant]
Yang et al., “Sheathless elasto-inertial particle focusing and continuous separation in a straight rectangular microchannel,” Lab Chip, Jan. 2011, 11(2):266-273. [cited by applicant]