IP Library › Granted Patent US 12,234,377
Granted Patent B2
US 12,234,377 · App. 17/048,114 · Granted Feb 25, 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 12,234,377
App. No.
17/048,114
Granted
Feb 25, 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 (28)

1. A method of forming a film on a surface of a substrate, wherein the substrate is a microwell device, the method comprising:

contacting the surface of the substrate with a composition,

wherein the composition comprises a coating reagent and a solvent,

wherein the coating reagent is a siloxane having a structure of Formula III:

wherein each R 3 is a substituted or unsubstituted alkyl, and at least one R 3 is a substituted or unsubstituted C3-C30 alkyl; and z is an integer from 1 to 10; and

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

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

forming the film of the coating reagent on the surface of the substrate.

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

3. The method of claim 1 , wherein the microwell device comprises an array comprising a plurality of wells each having volume from about 10 attoliters to about 100 microliters, and/or wherein contacting the surface of the substrate with the composition comprises filling the array with the composition.

4. The method of claim 3 , wherein the composition fills and/or wets at least 50% of the volume of the array.

5. The method of claim 1 , wherein forming the film of the coating reagent on the surface of the substrate comprises drying the composition on the surface of the substrate.

6. The method of claim 5 , further comprising, prior to drying the composition on the surface of the substrate, removing at least a portion of the composition from the substrate.

7. The method of claim 1 , wherein the film has a thickness of from about 1 nm to about 300 microns.

8. The method of claim 1 , wherein the substrate comprises a plurality of wells and the surface of the substrate comprises a first portion that is a surface of a well in the plurality of wells and a second portion that is a surface between two or more wells in the plurality of wells, and wherein the film has a greater thickness on the first portion compared to a thickness of the film on the second portion and/or wherein the film has a greater concentration of the coating reagent on the first portion compared to a concentration of the coating reagent on the second portion.

9. The method of claim 1 , wherein the substrate comprises a plurality of wells and less than about 10% of the wells are bridged and/or fluidically connected after an aqueous composition is added onto the film on the surface of the substrate and the plurality of wells comprising the aqueous composition are sealed with an oil.

10. The method of claim 1 , wherein the composition covers at least 95% of the surface of the substrate.

11. The method of claim 1 , wherein contacting the surface of the substrate with the composition comprises spraying the composition on the surface of the substrate.

12. The method of claim 1 , wherein forming the film of the coating reagent on the surface of the substrate comprises evaporating the solvent.

13. The method of claim 1 , wherein the film increases the hydrophobicity of the surface of the substrate.

14. The method of claim 1 , further comprising adding an oil onto the film on the surface of the substrate.

15. The method of claim 1 , wherein the substrate comprises a plastic, cyclic olefin copolymer (COC), cyclic olefin polymer (COP), polycarbonate, acrylic, fluoropolymer, silicone, glass, silicon, and/or metal surface.

16. The method of claim 1 , wherein the film prevents an aqueous composition from adhering and/or adsorbing to the surface or reduces the amount of the aqueous composition that adheres and/or adsorbs to the surface.

17. The method of claim 1 , wherein the film improves aqueous dewetting of the substrate during sealing of the substrate with an oil compared to the aqueous dewetting of the substrate during sealing in the absence of the film.

18. The method of claim 1 , wherein the coating reagent comprises at least one hydrophobic moiety, wherein the at least one hydrophobic moiety binds and/or interacts with the surface of the substrate.

19. The method of claim 1 , wherein the film on the surface of the substrate reduces the adherence of a biomolecule to the surface of the substrate compared to the adherence of the biomolecule to the surface of the substrate in the absence of the film.

20. The method of claim 1 , wherein the surface of the substrate is in contact with an aqueous composition prior to contacting the surface of the substrate with the composition comprising the coating reagent.

21. The method of claim 1 , further comprising contacting an aqueous composition to the surface of the substrate prior to contacting the surface of the substrate with the composition comprising the coating reagent.

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 Nov 23, 2020
From: RAMSEY, JOHN MICHAEL; HENLEY, WILLIAM HAMPTON
To: THE UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL
Reel/Frame 054441/0155 →
Continuity (2)
Provisional Application 62673343 · May 18, 2018
Related Publication 20210171798A1 · Jun 10, 2021
References Cited (139)
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 20120196774A1 · Fournier et al. · 2012 [cited by applicant]
US 20120202709A1 · Bergo · 2012 [cited by applicant]
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 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 2008088323 · 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 2013176767 · 2013 [cited by applicant]
WO 2013188872A1 · 2013 [cited by applicant]
WO 2014024162A1 · 2014 [cited by applicant]
WO 2015038767A1 · 2015 [cited by applicant]
WO 2017015529 · 2017 [cited by applicant]
WO 2017065854 · 2017 [cited by applicant]
WO 2017112025 · 2017 [cited by applicant]
WO 2020131182 · 2020 [cited by applicant]
WO 2020162996 · 2020 [cited by applicant]
Arkles, Barry “Hydrophobicity, Hydrophilicity and Silane Surface Modification” Gelest, Inc., Version 2.0, 84 pages (2011) https://www.pcimag.com/ext/resources/PCI/Home/Files/PDFs/Virtual_Supplier_Brochures/Gelest_Additi… [cited by applicant]
Berti et al. “Microfluidic-based electrochemical genosensor coupled to magnetic beads for hybridization detection” Talanta, 77:971-978 (2009). [cited by applicant]
Bhattacharyya et al. “Thermoplastic Microfluidic Device for On-Chip Purification of Nucleic Acids for Disposable Diagnostics” Analytical Chemistry, 78(3): 788-792 (2006) (Abstract only). [cited by applicant]
Boxshall et al. “Simple surface treatments to modify protein adsorption and cell attachment properties within a poly (dimethylsiloxane) micro-bioreactor” Surface Interface Analysis, 38(4):198-201 (2006) (Abstract only). [cited by applicant]
Cameron et al. “High fidelity, high yield production of microfluidic devices by hot embossing lithography: rheology and stiction” Lab on a Chip, 6(7):936-941 (2006) (Abstract only). [cited by applicant]
Carvalho et al. “Mild and Selective C—H Activation of COC Microfluidic Channels Allowing Covalent Multifunctional Coatings” Applied Materials & Interfaces, 9:16644-16650 (2017). [cited by applicant]
Chang et al. “Single molecule enzyme-linked immunosorbent assays: Theoretical considerations” Journal of Immunological Methods 378:102-115 (2012). [cited by applicant]
Definition of “immiscible,” dictionary.com, available at https://www.dictionary.com/browse/immiscible, accessed Jan. 8, 2021. [cited by applicant]
Dorre et al. “Techniques for single molecule sequencing” Bioimaging, 5:139-152 (1997). [cited by applicant]
Du et al. “SlipChip” Lap Chip, 9(16):2286-2292 (2009). [cited by applicant]
Gandhiraman et al. “High Efficiency Amine Functionalization of Cyclo Olefin Polymer Surfaces for Biodiagnostics” Journal of Materials Chemistry, 20:4116-4127 (2010). [cited by applicant]
Gibbs 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 et al. “Microfluidic flow control using selective hydrophobic patterning” SPIE, 3224:185-195 (1997). [cited by applicant]
Henley et al. “Fabrication of Microfluidic Devices Containing Patterned Microwell Arrays” Analytical Chemistry, 84:1776-1780 (2012). [cited by applicant]
Hindson et al. “High-Throughput Droplet Digital PCR System for Absolute Quantitation of DNA Copy Number” Analytical Chemistry, 83:8604-8610 (2011). [cited by applicant]
Hinz et al. “Polymer support for exonucleolytic sequencing” Journal of Biotechnology, 86:281-288 (2001). [cited by applicant]
Hjerten, Stellan “High-performance electrophoresis: Elimination of electroendosmosis and solute adsorption” Journal of Chromatography A, 347:191-198 (1985). [cited by applicant]
Holmberg et al. “The biotin-streptavidin interaction can be reversibly broken using water at elevated temperatures” Electrophoresis, 26:501-510 (2005). [cited by applicant]
Huang et al. “Highly sensitive mutation detection based on digital amplification coupled with hydrogel bead-array” ChemComm, 27:4094-4096 (2009). [cited by applicant]
Kalinina et al. “Nanoliter scale PCR with TaqMan detection” Nucleic Acids Research, 25(10):1999-2004 (1997). [cited by applicant]
Kan et al. “Isolation and Detection of Single Molecules on Paramagnetic Beads Using Sequential fluid Flows in Microfabricated Polymer Array Assemblies” Lab Chip, 12:977-985 (2012). [cited by applicant]
Kim et al. “Protein immobilization techniques for microfluidic assays” Biomicrofluidics, 7(4):041501 (2013). [cited by applicant]
Kitsara et al. “Integration of functional materials and surface modification for polymeric microfluidic systems” Journal of Micromechanics and Microengineering, 23(033001) 19 pages (2013). [cited by applicant]
Leamon et al. “A Massive parallel PicoTiterPlate based platform for discrete picoliter-scale polymerase chain reactions” Electrophoresis, 24:3769-3777 (2003). [cited by applicant]
Leamon et al. “Overview: methods and applications for droplet compartmentalization of biology” Nature Methods, 3(7):541-543 (2006). [cited by applicant]
Lindstrom et al. “PCR amplification and genetic analysis in a microwell cell culturing chip” Lab Chip, 9(24):3465-3471 (2009). [cited by applicant]
Lizardi et al. “Mutation detection and single-molecule counting using isothermal rolling-circle amplification” Nature Genetics, 19:225-232 (1998). [cited by applicant]
Malmstadt et al. “A Smart Microfluidic Affinity Chromatography Matrix Composed of Poly(N-isopropylacrylamide)-Coated Beads” Analytical Chemistry, 75:2943-2949 (2003). [cited by applicant]
Margulies et al. “Genome sequencing in microfabricated high-density picolitre reactors” Nature, 437(15):376-380 (2005). [cited by applicant]
Nagai et al. “Development of a Microchamber Array for Picoliter PCR” Analytical Chemistry, 73:1043-1047 (2001). [cited by applicant]
Nagai et al. “High-throughput PCR in silicon based microchamber array” Biosensors and Bioelectronics, 16(9-12):1015-1019 (2001) (Abstract only). [cited by applicant]
Nakano et al. “In Vitro Combinatorial Mutagenesis of the 65th and 222nd Positions of the Green Fluorescent Protein of Aequarea victoria” Biotechnology and Bioprocess Engineering, 7:311-315 (2002). [cited by applicant]
Osborne et al. “Single-Molecule Analysis of DNA Immobilized on Microspheres” Analytical Chemistry, 72:3678-3681 (2000). [cited by applicant]
Ottesen et al. “Microfluidic Digital PCR Enables Multigene Analysis of Individual Environmental Bacteria” Science, 314(5804):1464-1467 (2006). [cited by applicant]
Perez-Toralla et al. “New non-covalent strategies for stable surface treatment of thermoplastic chips” Lab on a Chip, 22(13):4409-4418 (2013). [cited by applicant]
Quanterix “Scientific Principle of Simoa (Single Molecule Array) Technology” (2 pages) (2013). [cited by applicant]
Rissin et al. “Single-Molecule enzyme-linked immunosorbent assay detects serum proteins at subfemtomolar concentrations” Nature Biotechnology, 28(6):595-599 (2010). [cited by applicant]
Rissin et al. “Multiplexed single molecule immunoassays” Lab on a Chip 13:2902-2911 (2013). [cited by applicant]
Rissin et al. “Simultaneous Detection of Single Molecules and Singulated Ensembles of Molecules Enables Immunoassays with Broad Dynamic Range” Analytical Chemistry 83:2279-2285 (2011). [cited by applicant]
Rissin, David M. “Single Molecule Detection: Analytical Applications and Fundamental Studies” Dissertation, Tufts University (183 pages) (Apr. 2007). [cited by applicant]
Schroeder et al. “User Configurable Microfluidic Device for Multiplexed Immunoassays Based on DNA-Directed Assembly” Analytical Chemistry, 81:1275-1279 (2009). [cited by applicant]
Selck 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):11129-11136 (20… [cited by applicant]
Shao 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 et al. “A Microfluidic System for Controlling Reaction Networks in Time” Angewandte Chemie, 42(7):768-772 (2003). [cited by applicant]
Song et al. “Direct Detection of Bacterial Genomic DNA at Sub-Femtomolar Concentrations Using Single Molecule Arrays” Analytical Chemistry 85:1932-1939 (2013). [cited by applicant]
Steinitz, Michael “Quantitation of the Blocking Effect of Tween 20 and Bovine Serum Albumin in ELISA Microwells,” Analytical Biochemistry 282, pp. 232-238 (2000). [cited by applicant]
Tan et al. “Monitoring the Reactions of Single Enzyme Molecules and Single Metal Ions” Analytical Chemistry, 69:4242-4248 (1997). [cited by applicant]
Taylor et al. “Impact of Surface Chemistry and Blocking Strategies on DNA Microarrays” Nucleic Acids Research, 31(16):e87 (2003). [cited by applicant]
Thermo Scientific “Instructions, StartingBlock Blocking Buffers” (3 pages) (2012). [cited by applicant]
Thompson et al. “Microfluidics for Single-Cell Genetic Analysis” Lab on a Chip, 14(17):3135-3142 (2014). [cited by applicant]
Tice et al. “Formation of Droplets and Mixing in Multiphase Microfluidics at Low Values of the Reynolds and the Capillary Numbers” Langmuir, 19:9127-9133 (2003). [cited by applicant]
Yelleswarapu 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):1083-1094 (2017) (Abstrac… [cited by applicant]
Yeo et al. “Microfluidic Devices for Bioapplications” Small, 7(1):12-48 (2011). [cited by applicant]
Zammatteo et al. “Comparison between Microwell and Bead Supports for the Detection of Human Cytomegalovirus Amplicons by Sandwich Hybridization” Analytical Biochemistry, 253:180-189 (1997). [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]
Extended European Search Report corresponding to European Patent Application No. 19866781.8 (9 pages) (dated Mar. 21, 2022). [cited by applicant]
Japanese Office Action corresponding to JP 2020-557995; dated Apr. 2, 2024, (6 pages, including English translation). [cited by applicant]