Methods of forming bioactive patterns using beam pen lithograpy-controlled cross-linking photopolymerization

Patent metadata

Field	Value
Publication number	US-2024385528-A1
Application number	US-202218695856-A
Country	US
Kind code	A1
Filing date	Sep 30, 2022
Priority date	Oct 1, 2021
Publication date	Nov 21, 2024
Grant date	—

Abstract

A method of forming a bioactive pattern on a substrate can include contacting a substrate comprising a prepolymer ink coated thereon with abeam pen lithography pen array. The prepolymer ink can include a photoinitiator, an acrylate, and a thiol-modified or acrylate-modified functional binding molecule. The method can further include irradiating the beam pen lithography pen array to transmit the radiation through the pens and out the exposed tip to controllably irradiate the prepolymer ink to initiate selectively photopolymerization of the prepolymer ink and form a pattern of thiol-functionalized cross-linked polymer printed indicia on the substrate; and exposing the pattern of the thiol-functionalized cross-linked polymer printed indicia in a biomolecule containing solution under conditions sufficient to bind the biomolecule to the thiol-functionalized cross-linked polymer printed indicia to form the bioactive pattern.

First claim

1 . A method of forming a bioactive pattern on a substrate, comprising:
contacting a substrate comprising a prepolymer ink coated thereon with a beam pen lithography pen array, the beam pen lithography pen array comprising a plurality of pens extending from a common substrate, each pen having a base attached to the common substrate and an oppositely disposed tip, a blocking layer is coated on each pen and has an aperture through which the tip is exposed, the prepolymer ink comprising a photoinitiator, an acrylate, and a thiol-modified or acrylate-modified functional binding molecule; irradiating the beam pen lithography pen array to transmit the radiation through the pens and out the exposed tip to controllably irradiate the prepolymer ink to initiate selectively photopolymerization of the prepolymer ink and form a pattern of thiol- or acrylate-functionalized cross-linked polymer printed indicia on the substrate; and exposing the pattern of the thiol-functionalized cross-linked polymer printed indicia in a biomolecule containing solution under conditions sufficient to bind the biomolecule to the thiol-functionalized cross-linked polymer printed indicia to form the bioactive pattern.

2 . The method of claim 1 , wherein the photoinitiator is one or more of diphenyl(2,4,6-trimethylbenzoyl) phosphine oxide (TPO), lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP), phenyl bis (2,4,6-trimethylbenzoyl) phosphine oxide (BAPO), camphorquinone (CQ), ethyl-dimethylamino benzoate (EDAB), Omnirad TPO-L, Omnirad 819, Irgacure 2959, Irgacure 651, Irgacure 184, Darocur 1173, Irgacure 819, Eosin-Y, Riboflavin, Camphorquinone and Isopropylthioxanthone (ITX).

3 . The method of claim 1 , wherein the acrylate is polyacrylate, polymethacrylate and poly(ethylene glycol diacrylate (PEGDA), poly(methyl methacrylate), poly(ethylene glycol) diacrylate (PEGDA) or poly(ethylene glycol) methacrylate.

4 . The method of claim 1 , wherein the binding molecule comprises a peptide with thiol or acrylate functionality and/or thiol- or acrylate-modified nucleotides.

5 . The method of claim 1 , wherein the binding molecule is thiol-modified and the thiol-modified functional binding molecule is one or more of thiol-PEG-biotin, 6-mercaptohexanoic acid (MHA), thiol-PEG-OH, thiol-PEG-COOH, thio-PEG-NH2, thiol-PEG-Azide.

6 . The method of claim 1 , wherein the biomolecule comprises one or more of cells, proteins, antibodies, lipids peptides, DNA, and RNA.

7 . The method of claim 1 , wherein the radiation has a wavelength of about 365 nm to about 503 nm.

8 . The method of g claim 1 , wherein the radiation comprises UV light.

9 . The method of claim 8 , wherein the UV light has a wavelength of about 365 nm to about 405 nm.

10 . The method of claim 1 , wherein the radiation is emitted from a digital micromirror device.

11 . The method of claim 1 , further comprising washing the thiol- or acrylate-functionalized cross-linked polymer printed indicia before immersing in the biomolecule containing solution.

12 . The method of claim 11 , comprising washing with one or more of acetone, ethanol, and water.

13 . The method of claim 1 , comprising printing the prepolymer indicial with a dwell time of about 0.05 s to about 100 s.

14 . The method of claim 1 , comprising applying a printing force of 1 mN to 10,000 mN when contacting the substrate with the beam pen lithography pen array.

15 . (canceled)

16 . The method of claim 1 , wherein the substrate is coated with gold prior to coating with the prepolymer ink.

17 . (canceled)

18 . The method of claim 1 , wherein the printed indicia have an average effective diameter of less than 300 nm.

19 . The method of claim 1 , comprising repeatedly contacting the substrate with the pen array and irradiating the pen array.

20 . The method of claim 1 , wherein the prepolymer ink is a first prepolymer ink and the thiol- or acrylate-functionalized cross-linked printed indicia are first thiol- or acrylate-functionalized cross-linked printed indicia adapted for binding a first biomolecule, the method further comprising coating the substrate having the first thiol- or acrylate-functionalized cross-linked printed indicia with a second prepolymer ink comprising a photoinitiator, an acrylate, and a thiol-modified or acrylate-modified binding molecule for binding a second biomolecule different from the first biomolecule, contacting the substrate coated with the second prepolymer ink with the beam pen lithography pen array and irradiating the beam pen lithography pen array to transmit the radiation through the pens and out the exposed tip to controllably irradiate the second prepolymer ink to initiate photopolymerization and form a pattern of second thiol- or acrylate-functionalized cross-linked polymer printed indicia on the substrate; and exposing the substrate having the pattern of first thiol- or acrylate-functionalized cross-linked polymer printed indicia and the pattern of second thiol- or acrylate-functionalized cross-linked polymer printed indicia to a biomolecule solution comprising the first and second biomolecules to bind the first and second biomolecules to the first and second thiol- or acrylate-functionalized cross-linked polymer printed indicia, respectively.

21 . The method of claim 1 , wherein the substrate is a silicon wafer, glass, fused silica, or quartz.

22 . The method of claim 1 , wherein the binding molecule is acrylate-modified and the acrylate-modified binding molecule is one or more of acrylate-PEG-biotin, acrylate-PEG-OH, acrylate-PEG-COOH, acrylate-PEG-NH2, acrylate-PEG-Azide.

Assignees

• Univ Northwestern
• Terra Print Llc

Inventors

• Mirkin Chad A
• Zhang Xinpeng
• Ivankin Andrey
• Ding Shaowei

Classifications

• G03F7/0002

  Lithographic processes using patterning methods other than those involving the exposure to radiation, e.g. by stamping · CPC title

• C09D11/101 Primary

  Inks specially adapted for printing processes involving curing by wave energy or particle radiation, e.g. with UV-curing following the printing · CPC title

• C12N2533/52

  Fibronectin; Laminin · CPC title

• C12N5/0068

  General culture methods using substrates (for specific animal cell type C12N5/06) · CPC title

• C09D11/03

  characterised by features other than the chemical nature of the binder · CPC title