IP Library › Granted Patent US 12,435,242
Granted Patent B2
US 12,435,242 · App. 19/021,410 · Granted Oct 7, 2025

Compositions, devices, and methods for improving a surface property of a substrate

Inventors: John Michael Ramsey (Chapel Hill, NC); William Hampton Henley (Chapel Hill, NC)
Assignee: The University of North Carolina at Chapel Hill
C09D183/08B01L3/502707C09D5/00C09D7/20B01L2300/165
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Quick Facts
Patent No.
US 12,435,242
App. No.
19/021,410
Granted
Oct 7, 2025
Kind
B2
Abstract

Described herein are compositions, devices, and methods for improving a surface property of a substrate. In some embodiments, the hydrophobicity and/or fluorocarbon-phobicity of the surface is increased. Some embodiments include compositions, devices and methods for improving bead loading and/or immiscible oil sealing of microwell array reactions on plastic microfluidic devices.

Claims (18)

1. A composition consisting of:

a coating reagent, wherein the coating reagent is chosen from 3-dodecylheptamethyltrisiloxane, 3-octylheptamethyltrisiloxane, n-octyltris (trimethylsiloxy) silane, 1,1,3,5,5-pentaphenyl-1,3,5-trimethyltrisiloxane, (3,3,3-trifluoropropyl) heptamethyltrisiloxane, methyltri-n-octylsilane, octylheptamethyltrisiloxane, ethylheptamethyltrisiloxane, propylheptamethyltrisiloxane, pentaheptamethyltrisiloxane, heptylheptamethyltrisiloxane, nonylheptamethyltrisiloxane, tridecaheptamethyltrisiloxane, pentadecylheptamethyltrisiloxane, tetradecylheptamethyltrisiloxane, heptadecylheptamethyltrisiloxane, hexadecylheptamethyltrisiloxane, nonadecylheptamethyltrisiloxane, octyldecylheptamethyltrisiloxane, hexylheptamethyltrisiloxane, undecaheptamethyltrisiloxane, duodecylheptamethyltrisiloxane, and any combination thereof; and

a solvent, wherein the solvent is a polysiloxane having a viscosity of less than 0.7 centistokes at 25° C.;

wherein the coating reagent is present in the composition in an amount from 0.01% to 5% by volume of the solvent.

2. The composition of claim 1 , wherein the solvent comprises hexamethyldisiloxane.

3. The composition of claim 1 , wherein the coating reagent is miscible with the solvent.

4. The composition of claim 1 , wherein the coating reagent is a trisiloxane.

5. The composition of claim 1 , wherein the coating reagent comprises 3-dodecylheptamethyltrisiloxane.

6. The composition of claim 1 , wherein the coating reagent is 3-dodecylheptamethyltrisiloxane and the solvent is hexamethyldisiloxane.

7. The composition of claim 6 , wherein the coating reagent is present in the composition in an amount of 1% by volume of the solvent.

8. The composition of claim 1 , wherein the coating reagent is present in the composition in an amount of 1% by volume of the solvent.

9. A substrate comprising a film on a surface of the substrate, wherein the substrate is a microwell device, and wherein the film comprises coating reagent remaining after a composition comprising a coating reagent and a solvent has been applied to the substrate and the solvent has been removed; wherein the coating reagent is chosen from 3-dodecylheptamethyltrisiloxane, 3-octylheptamethyltrisiloxane, n-octyltris (trimethylsiloxy) silane, 1,1,3,5,5-pentaphenyl-1,3,5-trimethyltrisiloxane, (3,3,3-trifluoropropyl) heptamethyltrisiloxane, methyltri-n-octylsilane, octylheptamethyltrisiloxane, ethylheptamethyltrisiloxane, propylheptamethyltrisiloxane, pentaheptamethyltrisiloxane, hexylheptamethyltrisiloxane, heptylheptamethyltrisiloxane, nonylheptamethyltrisiloxane, undecaheptamethyltrisiloxane, tridecaheptamethyltrisiloxane, tetradecylheptamethyltrisiloxane, pentadecylheptamethyltrisiloxane, hexadecylheptamethyltrisiloxane, heptadecylheptamethyltrisiloxane, octyldecylheptamethyltrisiloxane, nonadecylheptamethyltrisiloxane, duodecylheptamethyltrisiloxane, and any combination thereof and the solvent is a polysiloxane having a viscosity of less than 0.7 centistokes at 25° C.; and wherein the coating reagent is present in the composition in an amount from 0.01% to 5% by volume of the solvent.

10. The substrate of claim 9 , wherein the coating reagent is chosen from 3-dodecylheptamethyltrisiloxane, 3-octylheptamethyltrisiloxane, (3,3,3-trifluoropropyl) heptamethyltrisiloxane, n-octyltris (trimethylsiloxy) silane, methyltri-n-octylsilane, and any combination thereof.

11. The substrate of claim 9 , wherein the solvent comprises hexamethyldisiloxane.

12. The substrate of claim 9 , wherein the coating reagent comprises 3-dodecylheptamethyltrisiloxane.

13. The substrate of claim 9 , wherein the coating reagent is 3-dodecylheptamethyltrisiloxane and the solvent is hexamethyldisiloxane.

14. The substrate of claim 13 , wherein the coating reagent is present in the composition in an amount of 1% by volume of the solvent.

15. The substrate of claim 9 , wherein the coating reagent is present in the composition in an amount of 1% by volume of the solvent.

Assignments (2)
SECURITY INTEREST Recorded May 13, 2026
From: CODETTA BIO INC.
To: ANZU INDUSTRIAL CAPITAL PARTNERS III, L.P.; AICP III LP; ANZU INDUSTRIAL CAPITAL PARTNERS III QP, L.P.
Reel/Frame 074645/0206 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 17, 2025
From: RAMSEY, JOHN MICHAEL; HENLEY, WILLIAM HAMPTON
To: THE UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL
Reel/Frame 069911/0273 →
Continuity (3)
Division 17048114
Provisional Application 62673343 · May 18, 2018
Related Publication 20250163297A1 · May 22, 2025
References Cited (145)
US 4978540A · Lee · 1990 [cited by applicant]
US 5628833A · McCormack et al. · 1997 [cited by applicant]
US 6042709A · Parce et al. · 2000 [cited by applicant]
US 6143496A · Brown et al. · 2000 [cited by applicant]
US 6387331B1 · Hunter · 2002 [cited by applicant]
US 6565813B1 · Garyantes · 2003 [cited by applicant]
US 6589779B1 · McDevitt et al. · 2003 [cited by applicant]
US 6716629B2 · Hess et al. · 2004 [cited by applicant]
US 8222047B2 · Duffy et al. · 2012 [cited by applicant]
US 8236574B2 · Duffy et al. · 2012 [cited by applicant]
US 8460878B2 · Walt et al. · 2013 [cited by applicant]
US 8460879B2 · Walt et al. · 2013 [cited by applicant]
US 8492098B2 · Walt et al. · 2013 [cited by applicant]
US 8846415B2 · Duffy et al. · 2014 [cited by applicant]
US 9110025B2 · Rissin et al. · 2015 [cited by applicant]
US 9329174B2 · Noji et al. · 2016 [cited by applicant]
US 20020094533A1 · Hess et al. · 2002 [cited by applicant]
US 20020102578A1 · Dickinson et al. · 2002 [cited by applicant]
US 20020150723A1 · Oles et al. · 2002 [cited by applicant]
US 20030049620A1 · Lai et al. · 2003 [cited by applicant]
US 20030082576A1 · Jones et al. · 2003 [cited by applicant]
US 20030124716A1 · Hess et al. · 2003 [cited by applicant]
US 20040014168A1 · Schreiber et al. · 2004 [cited by applicant]
US 20050059048A1 · Gunderson et al. · 2005 [cited by applicant]
US 20060088857A1 · Attiya et al. · 2006 [cited by applicant]
US 20060228734A1 · Vann et al. · 2006 [cited by applicant]
US 20080008628A1 · Park et al. · 2008 [cited by applicant]
US 20090032401A1 · Ronaghi et al. · 2009 [cited by applicant]
US 20090146380A1 · Votaw et al. · 2009 [cited by applicant]
US 20100137143A1 · Rothberg et al. · 2010 [cited by applicant]
US 20100184036A1 · Fu · 2010 [cited by applicant]
US 20100248991A1 · Roesler et al. · 2010 [cited by applicant]
US 20100255471A1 · Clarke et al. · 2010 [cited by applicant]
US 20100317535A1 · Schmidt et al. · 2010 [cited by applicant]
US 20110009275A1 · Leamon et al. · 2011 [cited by applicant]
US 20110123413A1 · Abate et al. · 2011 [cited by applicant]
US 20110135819A1 · Chang et al. · 2011 [cited by applicant]
US 20120067908A1 · Brown · 2012 [cited by examiner]
US 20120196774A1 · Fournier et al. · 2012 [cited by applicant]
US 20120202709A1 · Bergo · 2012 [cited by applicant]
US 20120259252A1 · Thorn-Leeson · 2012 [cited by examiner]
US 20120322666A1 · Pham et al. · 2012 [cited by applicant]
US 20130345088A1 · Noji et al. · 2013 [cited by applicant]
US 20140323330A1 · Bergo · 2014 [cited by applicant]
US 20150151298A1 · Hobbs et al. · 2015 [cited by applicant]
US 20150211048A1 · Ramsey et al. · 2015 [cited by applicant]
US 20160095876A1 · Salamone · 2016 [cited by examiner]
US 20160216607A1 · Sato · 2016 [cited by applicant]
US 20160220995A1 · Atashbar et al. · 2016 [cited by applicant]
US 20160223531A1 · Noji et al. · 2016 [cited by applicant]
CN 1464071A · 2003 [cited by applicant]
CN 101553306A · 2009 [cited by applicant]
CN 101848765A · 2010 [cited by applicant]
CN 104540901A · 2015 [cited by applicant]
EP 1245655A2 · 2002 [cited by applicant]
JP H0688025A · 1994 [cited by applicant]
JP 2002502955A · 2002 [cited by applicant]
JP 2002322299A · 2002 [cited by applicant]
JP 2003009890A · 2003 [cited by applicant]
JP 2004518115A · 2004 [cited by applicant]
JP 2007525963A · 2007 [cited by applicant]
JP 2010515566A · 2010 [cited by applicant]
JP 2010519896A · 2010 [cited by applicant]
JP 2013536302A · 2013 [cited by applicant]
JP 2021509776A · 2021 [cited by applicant]
WO 9111533A1 · 1991 [cited by applicant]
WO 9637630A1 · 1996 [cited by applicant]
WO 9939829A1 · 1999 [cited by applicant]
WO 2005071056A1 · 2005 [cited by applicant]
WO 2007092713A2 · 2007 [cited by applicant]
WO 2008088323A2 · 2008 [cited by applicant]
WO 2009078812A1 · 2009 [cited by applicant]
WO 2009145022A1 · 2009 [cited by applicant]
WO 2012004353A1 · 2012 [cited by applicant]
WO 2012027238A1 · 2012 [cited by applicant]
WO 2012055069A1 · 2012 [cited by applicant]
WO 2013176767A1 · 2013 [cited by applicant]
WO 2013188872A1 · 2013 [cited by applicant]
WO 2014024162A1 · 2014 [cited by applicant]
WO 2015038767A1 · 2015 [cited by applicant]
WO 2017015529A1 · 2017 [cited by applicant]
WO 2017065854A2 · 2017 [cited by applicant]
WO 2017112025A2 · 2017 [cited by applicant]
WO 2020131182A2 · 2020 [cited by applicant]
WO 2020162996A2 · 2020 [cited by applicant]
European Office Action corresponding to EP 13794324.7; mailed Jan. 25, 2019 (4 pages). [cited by applicant]
Extended European Search Report corresponding to European Patent Application No. 19866781.8 (9 pages) (dated Mar. 21, 2022). [cited by applicant]
International Search Report and the Written Opinion of the International Searching Authority corresponding to International Patent Application No. PCT/US2019/032389 (12 pages) (mailed Apr. 21, 2020). [cited by applicant]
Japanese Office Action corresponding to JP 2020-557995; dated Apr. 2, 2024, (6 pages, including English translation). [cited by applicant]
Arkles, Barry , “Hydrophobicity, Hydrophilicity and Silane Surface Modification”, Gelest, Inc., Version 2.0, https://www.pcimag.com/ext/resources/PCI/Home/Files/PDFs/Virtual_Supplier_Brochures/Gelest_Additives.pdf, 2011… [cited by applicant]
Berti, Francesca , et al., “Microfluidic-based electrochemical genosensor coupled to magnetic beads for hybridization detection”, Talanta, 77(3), 2009, 971-978. [cited by applicant]
Bhattacharyya, Arpita , et al., “Thermoplastic Microfluidic Device for On-Chip Purification of Nucleic Acids for Disposable Diagnostics”, Analytical Chemistry, 78(3) (Abstract only), 2006, 788-792. [cited by applicant]
Boxshall, Keir , et al., “Simple surface treatments to modify protein adsorption and cell attachment properties within a poly(dimethylsiloxane) micro-bioreactor”, Surface Interface Analysis, 38(4) (Abstract only), 2006,… [cited by applicant]
Cameron, Neil S., et al., “High fidelity, high yield production of microfluidic devices by hot embossing lithography: rheology and stiction”, Lab on a Chip, 6(7) (Abstract only), 2006, 936-941. [cited by applicant]
Carvalho, Rui Rijo , et al., “Mild and Selective C-H Activation of COC Microfluidic Channels Allowing Covalent Multifunctional Coatings”, Applied Materials & Interfaces, 9(19), 2017, 16644-16650. [cited by applicant]
Chang, Lei , et al., “Single molecule enzyme-linked immunosorbent assays: Theoretical considerations”, Journal of Immunological Methods, 378(1-2), 2012, 102-115. [cited by applicant]
dictionary.com , “Definition of “immiscible””, available at https://www.dictionary.com/browse/immiscible, accessed Jan. 8, 2021. [cited by applicant]
Dörre, Klaus , et al., “Techniques for single molecule sequencing”, Bioimaging, 5(3), 1997, 139-152. [cited by applicant]
Du, Wenbin , et al., “SlipChip”, Lap Chip, 9(16), 2009, 2286-2292. [cited by applicant]
Gandhiraman, Ram P., et al., “High Efficiency Amine Functionalization of Cyclo Olefin Polymer Surfaces for Biodiagnostics”, Journal of Materials Chemistry, 20, 2010, 4116-4127. [cited by applicant]
Gibbs, Judy , et al., “Effective Blocking Procedures in ELISA Assays”, Corning, 2001-2017 Corning Incorporated, All Rights Reserved, Oct. 2017, CLS-DD-AN-456 REV1, 4 pages. [cited by applicant]
Handique, K. , et al., “Microfluidic flow control using selective hydrophobic patterning”, SPIE, 3224, 1997, 185-195. [cited by applicant]
Henley, W. Hampton, et al., “Fabrication of Microfluidic Devices Containing Patterned Microwell Arrays”, Analytical Chemistry, 84(3), 2012, 1776-1780. [cited by applicant]
Hindson, Benjamin J., et al., “High-Throughput Droplet Digital PCR System for Absolute Quantitation of DNA Copy Number”, Analytical Chemistry, 83(22), 2011, 8604-8610. [cited by applicant]
Hinz, M. , et al., “Polymer support for exonucleolytic sequencing”, Journal of Biotechnology, 86(3), 2001, 281-288. [cited by applicant]
Hjerten, Stellan , “High-performance electrophoresis : Elimination of electroendosmosis and solute adsorption”, Journal of Chromatography A, 347, 1985, 191-198. [cited by applicant]
Holmberg, Anders , et al., “The biotin-streptavidin interaction can be reversibly broken using water at elevated temperatures”, Electrophoresis, 26(3), 2005, 501-510. [cited by applicant]
Huang, Huan , et al., “Highly sensitive mutation detection based on digital amplification coupled with hydrogel bead-array”, Chemical Communications, 27, 2009, 4094-4096. [cited by applicant]
Kalinina, Olga , et al., “Nanoliter scale PCR with TaqMan detection”, Nucleic Acids Research, 25(10), 1997, 1999-2004. [cited by applicant]
Kan, Cheuk W., et al., “Isolation and detection of single molecules on paramagnetic beads using sequential fluid flows in microfabricated polymer array assemblies”, Lab on a Chip, 12, 2012, 977-985. [cited by applicant]
Kim, Dohyun , et al., “Protein immobilization techniques for microfluidic assays”, Biomicrofluidics, 7(4):041501, 2013. [cited by applicant]
Kitsara, Maria , et al., “Integration of functional materials and surface modification for polymeric microfluidic systems”, Journal of Micromechanics and Microengineering, 23(033001), 2013, (19 pages). [cited by applicant]
Leamon, John H., et al., “A massively parallel PicoTiterPlate™ based platform for discrete picoliter-scale polymerase chain reactions”, Electrophoresis, 24(21), 2003, 3769-3777. [cited by applicant]
Leamon, John H., et al., “Overview: methods and applications for droplet compartmentalization of biology”, Nature Methods, 3(7), 2006, 541-543. [cited by applicant]
Lindstrom, Sara , et al., “PCR amplification and genetic analysis in a microwell cell culturing chip”, Lab Chip 9(24), 2009, 3465-3471. [cited by applicant]
Lizardi, Paul M., et al., “Mutation detection and single-molecule counting using isothermal rolling-circle amplification”, Nature Genetics, 19, 1998, 225-232. [cited by applicant]
Malmstadt, Noah , et al., “A smart microfluidic affinity chromatography matrix composed of poly (N-isopropylacrylamide)-coated beads”, Analytical Chemistry, 75(13), 2003, 2943-2949. [cited by applicant]
Margulies, Marcel , et al., “Genome sequencing in microfabricated high-density picolitre reactors”, Nature, 437 (7057), 2005, 376-380. [cited by applicant]
Nagai, Hidenori , et al., “Development of a microchamber array for picoliter PCR”, Analytical Chemistry, 73(5), 2001, 1043-1047. [cited by applicant]
Nagai, Hidenori , et al., “High-throughput PCR in silicon based microchamber array”, Biosensors and Bioelectronics, 16(9-12) (Abstract only), 2001, 1015-1019. [cited by applicant]
Nakano, Hideo , et al., “In vitro combinatorial mutagenesis of the 65th and 222nd positions of the green fluorescent protein ofAequarea victoria”, Biotechnology and Bioprocess Engineering, 7, 2002, 311-315. [cited by applicant]
Osborne, Mark A., et al., “Single-molecule analysis of DNA immobilized on microspheres”, Analytical Chemistry, 72(15), 2007, 3678-3681. [cited by applicant]
Ottesen, Elizabeth A., et al., “Microfluidic Digital PCR Enables Multigene Analysis of Individual Environmental Bacteria”, Science, 314(5804), 2006, 1464-1467. [cited by applicant]
Perez-Toralla, Karla, et al., “New non-covalent strategies for stable surface treatment of thermoplastic chips”, Lab on a Chip, 22(13), 2013, 4409-4418. [cited by applicant]
Quanterix , “Scientific Principle of Simoa (Single Molecule Array) Technology”, (2 pages), 2013. [cited by applicant]
Rissin, David M, et al., “Multiplexed single molecule immunoassays”, Lab on a Chip, 13(15), 2013, 2902-2911. [cited by applicant]
Rissin, David M, et al., “Simultaneous Detection of Single Molecules and Singulated Ensembles of Molecules Enables Immunoassays with Broad Dynamic Range”, Analytical Chemistry, 83(6), 2011, 2279-2285. [cited by applicant]
Rissin, David M, “Single Molecule Detection: Analytical Applications and Fundamental Studies”, Dissertation, Tufts University, Apr. 2007, (183 pages). [cited by applicant]
Rissin, David M, et al., “Single-molecule enzyme-linked immunosorbent assay detects serum proteins at subfemtomolar concentrations”, Nature Biotechnology, 28(6), 2010, 595-599. [cited by applicant]
Schroeder, Hendrik , et al., “User Configurable Microfluidic Device for Multiplexed Immunoassays Based on DNA-Directed Assembly”, Anal. Chem., 81(3), 2009, 1275-1279. [cited by applicant]
Selck, David A, et al., “Increased Robustness of Single-Molecule Counting with Microfluidics, Digital Isothermal Amplification, and a Mobile Phone versus Real-Time Kinetic Measurements”, Analytical Chemistry, 85(22), 20… [cited by applicant]
Selck, David A., et al., “Increased Robustness of Single-Molecule Counting with Microfluidics, Digital Isothermal Amplification, and a Mobile Phone versus Real-Time Kinetic Measurements”, Analytical Chemistry, 85(22) (A… [cited by applicant]
Shao, Keke , et al., “Emulsion PCR: A High Efficient Way of PCR Amplification of Random DNA Libraries in Aptamer Selection”, PLoS One, 6(9):e24910, 2011. [cited by applicant]
Song, Helen , et al., “A Microfluidic System for Controlling Reaction Networks in Time”, Angewandte Chemie, 42(7), 2003, 768-772. [cited by applicant]
Song, Linan , et al., “Direct Detection of Bacterial Genomic DNA at Sub-Femtomolar Concentrations Using Single Molecule Arrays”, Analytical Chemistry, 85(3), 2013, 1932-1939. [cited by applicant]
Steinitz, Michael , “Quantitation of the Blocking Effect of Tween 20 and Bovine Serum Albumin in ELISA Microwells”, Analytical Biochemistry, 282(2), 2000, 232-238. [cited by applicant]
Tan, Weihong , et al., “Monitoring the reactions of single enzyme molecules and single metal ions”, Analytical Chemistry, 69(20), 1997, 4242-4248. [cited by applicant]
Taylor, Scott , et al., “Impact of Surface Chemistry and Blocking Strategies on DNA Microarrays”, Nucleic Acids Research, 31(16): e87, 2003, 1-19. [cited by applicant]
Thermo Scientific , “Instructions: StartingBlock Blocking Buffers”, Instruction Sheet, 2012, (3 pages). [cited by applicant]
Thompson, A. M. , et al., “Microfluidics for Single-Cell Genetic Analysis”, Lab on a Chip, 14(17), 2014, 3135-3142. [cited by applicant]
Tice, Joshua D., et al., “Formation of Droplets and Mixing in Multiphase Microfluidics at Low Values of the Reynolds and the Capillary Numbers”, Langmuir, 19(22), 2003, 9127-9133. [cited by applicant]
Yelleswarapu, Venkata R., et al., “Ultra-high throughput detection (1 million droplets per second) of fluorescent droplets using a cell phone camera and time domain encoded optofluidics”, Lab on a Chip, 6(17) (Abstract … [cited by applicant]
Yelleswarapu, Venkata R, et al., “Ultra-high throughput detection (1 million droplets per second) of fluorescent droplets using a cell phone camera and time domain encoded optofluidics”, Lap on a Chip, 17(6), 2017, 1083… [cited by applicant]
Yeo, Leslie Y., et al., “Microfluidic Devices for Bioapplications”, Small, 7(1), 2011, 12-48. [cited by applicant]
Zammatteo, Nathalie , et al., “Comparison between microwell and bead supports for the detection of human cytomegalovirus amplicons by sandwich hybridization”, Analytical Biochemistry, 253(2), 1997, 180-189. [cited by applicant]