IP Library › Granted Patent US 12,187,996
Granted Patent B2
US 12,187,996 · App. 18/056,035 · Granted Jan 7, 2025

Open-top microfluidic devices and methods for simulating a function of a tissue

Inventors: Antonio Varone (Cambridge, MA); Norman Wen (Cambridge, MA); Daniel Levner (Cambridge, MA); Richard Novak (Cambridge, MA); Lori McPartlin (Cambridge, MA); Donald E. Ingber (Cambridge, MA); Youngjae Choe (Cambridge, MA); Lian Leng (Cambridge, MA); Justin K. Nguyen (Cambridge, MA)
Assignee: President and Fellows of Harvard College
C12M23/16C12M21/08C12M25/02C12M25/14C12N5/0629C12N5/0656C12N5/0679C12N5/069B01L3/5027B01L2300/069C12M3/04C12M29/10C12M41/46
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 12,187,996
App. No.
18/056,035
Granted
Jan 7, 2025
Kind
B2
Abstract

A device for simulating a function of a tissue includes a first structure, a second structure, and a membrane. The first structure defines a first chamber. The first chamber includes a matrix disposed therein and an opened region. The second structure defines a second chamber. The membrane is located at an interface region between the first chamber and the second chamber. The membrane includes a first side facing toward the first chamber and a second side facing toward the second chamber. The membrane separates the first chamber from the second chamber.

Claims (11)

1. A microfluidic device comprising:

a gel chamber with a gel matrix disposed therein, the gel chamber including an open top surface region;

a fluidic chamber wherein a first interface region is formed between the gel chamber and the fluidic chamber;

a membrane disposed at the first interface region, the membrane including a first side facing the gel chamber and a second side facing the fluidic chamber; and

a movable cover disposed on the gel chamber above the gel matrix, the movable cover configured to provide access to the gel chamber, wherein the movable cover defines an aperture having one end configured to align with the open top surface region of the gel chamber when the movable cover is disposed on the gel chamber such that a fluid material entering the aperture flows through the movable cover and into the open top surface region of the gel chamber.

2. The microfluidic device of claim 1 , wherein the gel matrix includes fibroblasts and keratinocytes in or on the gel matrix.

3. The microfluidic device of claim 2 , wherein the aperture is a channel.

4. The microfluidic device of claim 3 , wherein the channel is circular, oval, spiral, or irregularly shaped.

5. The microfluidic device of claim 1 , wherein the gel matrix disposed in the gel chamber is secured by structural anchors.

6. The microfluidic device of claim 1 , wherein the aperture is a channel.

7. The microfluidic device of claim 6 , wherein the channel is circular, oval, spiral, or irregularly shaped.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 20, 2025
From: NGUYEN, JUSTIN; CHOE, YOUNGJAE; NOVAK, RICHARD; LENG, LIAN; LEVNER, DANIEL; WEN, NORMAN; VARONE, ANTONIO; INGBER, DONALD E.; MCPARTLIN, LORI A.
To: PRESIDENT AND FELLOWS OF HARVARD COLLEGE
Reel/Frame 070276/0443 →
Continuity (3)
Continuation 15781078
Provisional Application 62263225 · Dec 4, 2015
Related Publication 20230159872A1 · May 25, 2023
References Cited (53)
US 7485454B1 · Jury · 2009 [cited by applicant]
US 7807453B2 · Quinn · 2010 [cited by applicant]
US 8647861B2 · Ingber · 2014 [cited by applicant]
US 10988723B1 · Hatch et al. · 2021 [cited by applicant]
US 20030017142A1 · Toner et al. · 2003 [cited by applicant]
US 20060240548A1 · Deutsch · 2006 [cited by applicant]
US 20070141552A1 · Warren · 2007 [cited by applicant]
US 20070292939A1 · Chen · 2007 [cited by examiner]
US 20110053207A1 · Hoganson et al. · 2011 [cited by applicant]
US 20110053270A1 · Chang et al. · 2011 [cited by applicant]
US 20110081677A1 · Luo · 2011 [cited by applicant]
US 20110082056A1 · Park · 2011 [cited by applicant]
US 20110183312A1 · Huang · 2011 [cited by applicant]
US 20110275543A1 · Deutsch · 2011 [cited by applicant]
US 20120135452A1 · Shuler · 2012 [cited by examiner]
US 20120164679A1 · Vrouwe · 2012 [cited by applicant]
US 20120195810A1 · Cohen · 2012 [cited by applicant]
US 20140038279A1 · Ingber · 2014 [cited by applicant]
US 20140055853A1 · Corwin · 2014 [cited by applicant]
US 20140093905A1 · Inger · 2014 [cited by applicant]
US 20140186414A1 · Ingber · 2014 [cited by examiner]
US 20140335496A1 · Grego · 2014 [cited by examiner]
US 20140342445A1 · Ingber et al. · 2014 [cited by applicant]
US 20140349396A1 · West · 2014 [cited by applicant]
US 20150004077A1 · Wikswo · 2015 [cited by applicant]
US 20150252328A1 · Woodruff et al. · 2015 [cited by applicant]
US 20160136333A1 · Reichmann · 2016 [cited by examiner]
EP 2639293 · 2021 [cited by applicant]
JP 2011092180 · 2011 [cited by applicant]
JP 2011528232 · 2011 [cited by applicant]
KR 20140040704 · 2014 [cited by applicant]
WO 2004059299A1 · 2004 [cited by applicant]
WO 2010122945A1 · 2010 [cited by applicant]
WO 2013085909 · 2013 [cited by applicant]
WO 2015138032 · 2015 [cited by applicant]
WO 2015138034A2 · 2015 [cited by applicant]
Iliescu et al., A practical guide for the fabrication of microfluidic devices using glass and silicon, 2012, Biomicrofluidics, 6, 016505 (Year: 2012). [cited by examiner]
Notice of Eligibility of Grant and Examination Report in Singapore Application No. 11201804706U, dated Aug. 4, 2022 (6 pages). [cited by applicant]
Bhatia et al., “Microfluidic organs-on-chips,”Nature biotechnology, Aug. 5, 2014 (Aug. 5, 2014), vol. 32, No. 8, pp. 760-772. [cited by applicant]
Carlson, M.W. et al., “Three-Dimensional Tissue Models of Normal and Diseased Skin,” Current Protocols in Cell Biology, Supplement 41, Dec. 2008, pp. 19.9.1-19.9.17 (17 pages). [cited by applicant]
De Oliveira, Z.N.P et al., “Immunological mapping in hereditary epidermolysis bullosa,” An Bras Dermatol., 85(6), 2010, Rio de Janeiro, pp. 856-861 (6 pages). [cited by applicant]
Jean, J. et al., “Bioengineered Skin: The Self-Assembly Approach,” Journal of Tissue Science & Engineering, 2011, S:5, DOI: 10.4172/2157-7552.S5-001 (10 pages). [cited by applicant]
Keenan, T.M. et al., “A New Method for Studying Gradient-Induced Neutrophil Desensitization Based on an Open Microfluidic Chamber,” Lab Chip, Jan. 7, 2010, 10(1), pp. 116-122, DOI:10.1039/b913494h (14 pages). [cited by applicant]
Wagner et al., “A Dynamic Multi-Organ-Chip for Long-Term Cultivation and Substance Testing Proven by 3D Human Liver and Skin Tissue Co-Culture,” Lab on a Chip, May 7, 2013 (May 7, 2013), vol. 13, pp. 3538-3547. [cited by applicant]
Partial European Search Report in European Patent Application No. 16871655.3, dated May 19, 2019 (11 pages). [cited by applicant]
Lovchik, R.D. et al., “Overflow Microfluidic Networks,” 14th International Conference on Miniaturized Systems for Chemistry and Life Sciences, Oct. 3-7, 2010, Groningen, The Netherlands, pp. 989-991 (3 pages). [cited by applicant]
Maas-Szabowski, N. et al., “Keratinocyte Growth Regulation in Defined Organotypic Cultures Through IL-1-Induced Keratinocyte Growth Factor Expression in Resting Fibroblasts,” Journal of Investigative Dermatology, 2000, … [cited by applicant]
Wright, G.A. et al., “On-Chip Open Microfluidic Devices for Chemotaxis Studies,” Microsc Microanal., Aug. 2012, 18(4), pp. 816-828, DOI:10.1017/S1431927612000475 (22 pages). [cited by applicant]
“A new—and heart-warming—biomaterial for tissue engineering?”, Harsjorg Wyss Institute for Biologically Inspired Engineering, May 7, 2013 (3 pages). [cited by applicant]
International Search Report in International Application No. PCT/US2016/064798, mailed Mar. 17, 2017 (4 pages). [cited by applicant]
Written Opinion in International Application No. PCT/US2016/064798, mailed Mar. 17, 2017 (7 pages). [cited by applicant]
Tenenbaum-Katan et al., “Biomimetics of fetal alveolar flow phenomena using microfluidics,” Biomicrofluidics 9, pp. 014120-0-014120-13 (2015) 14 pages. [cited by applicant]
Muller et al., “Culturing of Human Nasal Epithelial Cells at the Air Liquid Interface”, 2013, J. Vis. Exp. (80), e50646, pp. 1-7 (Year: 2013). [cited by applicant]