IP Library Granted Patent US 12,325,846
Granted Patent B2
US 12,325,846 · App. 18/604,469 · Granted Jun 10, 2025

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

Inventors: Antonio Varone (Newton, MA); Norman Wen (Newton, MA); Daniel Levner (Brookline, MA); Richard Novak (Jamaica Plain, MA); Lori McPartlin (North Billerica, MA); Donald E. Ingber (Boston, MA); Youngjae Choe (Somerville, MA); Lian Leng (LaSalle, CA); Justin K. Nguyen (Medford, 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 12,325,846
App. No.
18/604,469
Granted
Jun 10, 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 (10)

1. A method of seeding cells, comprising:

(a) providing a microfluidic device comprising a first chamber, the first chamber including a three-dimensional gel matrix disposed therein, and a second chamber, said second chamber separated from the first chamber by a membrane, the gel matrix positioned under a removable cover that comprises a fluidic chamber, wherein said fluidic chamber of said removable cover substantially aligns with all of an open top region of the first chamber;

(b) removing the removable cover thereby exposing the gel matrix; and

(c) seeding cells within the gel matrix.

2. The method of claim 1 , wherein the gel matrix has a patterned surface.

3. The method of claim 1 , wherein the membrane includes endothelial cells.

4. The method of claim 1 , wherein the second chamber includes fluidics configured to supply the cells with culture fluid.

5. The method of claim 1 , further comprising (d) culturing the cells submerged in culture fluid.

6. The method of claim 5 , further comprising (e) culturing the cells in air without culture media.

7. The method of claim 1 , wherein said cells are intestinal cells.

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 (4)
Continuation 17820174 · Aug 16, 2022
Continuation 15781078
Provisional Application 62263225 · Dec 4, 2015
Related Publication 20240218309A1 · Jul 4, 2024
References Cited (55)
US 7485454B1 · Jury et al. · 2009 [cited by applicant]
US 7807453B2 · Quinn et al. · 2010 [cited by applicant]
US 8647861B2 · Ingber et al. · 2014 [cited by applicant]
US 10988723B1 · Hatch · 2021 [cited by examiner]
US 20030017142A1 · Toner et al. · 2003 [cited by applicant]
US 20060240548A1 · Deutsch et al. · 2006 [cited by applicant]
US 20070141552A1 · Warren et al. · 2007 [cited by applicant]
US 20070292939A1 · Chen · 2007 [cited by applicant]
US 20110053207A1 · Hoganson et al. · 2011 [cited by applicant]
US 20110053270A1 · Chang · 2011 [cited by examiner]
US 20110081677A1 · Luo · 2011 [cited by applicant]
US 20110082056A1 · Park et al. · 2011 [cited by applicant]
US 20110183312A1 · Huang · 2011 [cited by applicant]
US 20110275543A1 · Deutsch · 2011 [cited by applicant]
US 20120135452A1 · Shuler et al. · 2012 [cited by applicant]
US 20120164679A1 · Vrouwe et al. · 2012 [cited by applicant]
US 20120195810A1 · Cohen · 2012 [cited by applicant]
US 20140038279A1 · Ingber et al. · 2014 [cited by applicant]
US 20140055853A1 · Corwin et al. · 2014 [cited by applicant]
US 20140093905A1 · Ingber et al. · 2014 [cited by applicant]
US 20140186414A1 · Ingber et al. · 2014 [cited by applicant]
US 20140335496A1 · Grego · 2014 [cited by examiner]
US 20140342445A1 · Ingber et al. · 2014 [cited by applicant]
US 20140349396A1 · West et al. · 2014 [cited by applicant]
US 20150004077A1 · Wikswo et al. · 2015 [cited by applicant]
US 20150252328A1 · Woodruff et al. · 2015 [cited by applicant]
US 20160136333A1 · Reichmann · 2016 [cited by applicant]
EP 2639293B1 · 2021 [cited by applicant]
JP 2011092180A · 2011 [cited by applicant]
JP 2011528232A · 2011 [cited by applicant]
KR 20140040704A · 2014 [cited by applicant]
WO 2004059299A1 · 2004 [cited by applicant]
WO 2010122945A1 · 2010 [cited by applicant]
WO 2013085909 · 2013 [cited by applicant]
WO 2015138032A2 · 2015 [cited by applicant]
WO 2015138034A2 · 2015 [cited by applicant]
Müller 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 examiner]
Notice for Acceptance in Australia Application No. 2021261826, mailed Dec. 1, 2023 (4 pages). [cited by applicant]
Examination report No. 3 in Australia Application No. 2021261826, mailed Nov. 13, 2023; (3 pages). [cited by applicant]
Notice for Eligibility of Grant and Examination Report in Singapore Application No. 11201804706U, mailed Aug. 4, 2022 (6 pages). [cited by applicant]
Iliescu et al., “A practical guide for the fabrication of microfluidic devices using glass and silicon.” Biomicrofluidics 6.1 (2012). [cited by applicant]
Bhatia et al., “Microfluidic organs-on-chips,” Nature biotechnology, vol. 32, No. 8, pp. 760-772 (2014). [cited by applicant]
Carlson et al., “Three-Dimensional Tissue Models of Normal and Diseased Skin,” Current Protocols in Cell Biology, Supplement 41 pp. 19.9.1-19.9.17 (2008). [cited by applicant]
De Oliveira et al., “Immunological mapping in hereditary epidermolysis bullosa,” An Bras Dermatol., 85(6), Rio de Janeiro, pp. 856-861 (2010). [cited by applicant]
Jean et al., “Bioengineered Skin: The Self-Assembly Approach,” Journal of Tissue Science & Engineering, S:5, DOI:10.4172/2157-7552.S5-001 (2011). [cited by applicant]
Keenan et al., “A New Method for Studying Gradient-Induced Neutrophil Desensitization Based on an Open Microfluidic Chamber,” Lab Chip, Jan. 7, 10(1), pp. 116-122, DOI: 10.1039/b913494h (2010). [cited by applicant]
Partial European Search Report in European Patent Application No. 16871655.3, dated May 29, 2019 (11 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, vol. 13, pp. 3538-3547 (2013). [cited by applicant]
Lovchik et al., “Overflow Microfluidic Networks,” 14th International Conference on Miniaturized Systems for Chemistry and Life Sciences, Oct. 3-7, Groningen, The Netherlands, pp. 989-991 (2010). [cited by applicant]
Maas-Szabowski et al., “Keratinocyte Growth Regulation in Defined Organotypic Cultures Through IL-I-Induced Keratinocyte Growth Factor Expression in Resting Fibroblasts,” Journal ofInvestigative Dermatology, 114, pp. 10… [cited by applicant]
Wright et al., “On-Chip Open Microfluidic Devices for Chemotaxis Studies,” Microsc Microanal., 18(4), pp. 816-828, DOI:10.1017/SI431927612000475 (2012). [cited by applicant]
“A new—and heart-warming—biomaterial for tissue engineering?”, Harsjorg Wyss Institute for Biologically Inspired Engineering (2013). [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). [cited by applicant]