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Advancing Biocapture Substrates via Chemical Lift-Off Lithography Huan H. Cao, Nako Nakatsuka, Wei-Ssu Liao, Andrew C. Serino, Sarawut Cheunkar, Hongyan Yang, Paul S. Weiss, and Anne M. Andrews Chem. Mater., Just Accepted Manuscript • DOI: 10.1021/acs.chemmater.7b01970 • Publication Date (Web): 24 Jul 2017 Downloaded from http://pubs.acs.org on July 24, 2017
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Chemistry of Materials
Advancing Biocapture Substrates via Chemical Lift-Off Lithography
Huan H. Cao,1,2 Nako Nakatsuka, 1,2 Wei-Ssu Liao,1,2 Andrew C. Serino,1,2,3 Sarawut Cheunkar,1,2 Hongyan Yang,4 Paul S. Weiss,*1,2,3 and Anne M. Andrews*1,2,4 1California
NanoSystems Institute, University of California, Los Angeles, Los Angeles,
CA 90095, United States 2Department
of Chemistry and Biochemistry, University of California, Los Angeles, Los
Angeles, CA 90095, United States 3Department
of Materials Science and Engineering, University of California, Los Angeles,
Los Angeles, CA 90095, United States 4Department
of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience
and Human Behavior, and Hatos Center for Neuropharmacology, University of California, Los Angeles, Los Angeles, CA 90095, United States
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ABSTRACT: Creating small-molecule-functionalized platforms for high-throughput screening or biosensing applications requires precise placement of probes on solid substrates and the ability to capture and to sort targets from multicomponent samples. Here, chemical lift-off lithography was used to fabricate large-area, high-fidelity patterns of small-molecule probes. Lift-off lithography enables biotin-streptavidin patterned recognition with feature sizes ranging from micrometers to below 30 nm. Subtractive patterning via lift-off facilitated insertion of a different type of molecule and thus, multiplexed side-by-side placement of small molecule probes such that binding partners were directed to cognate probes from solution. Small molecules mimicking endogenous neurotransmitters were patterned using lift-off lithography to capture native membraneassociated receptors. We characterized patterning of alkanethiols that self-assemble on Au having different terminal functional groups to expand the library of molecules amenable to lift-off lithography enabling a wide range of functionalization chemistries for use with this simple and versatile patterning method.
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Chemistry of Materials
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INTRODUCTION To produce multiplexed, functional, biocapture platforms for high-throughput screening or biosensing applications, surface patterning and immobilization strategies are needed to anchor molecules on solid substrates for capturing and sorting respective binding partners from complex mixtures in solution or in vivo.1-11 Although, in vivo sensing to date has been based largely on electrochemical12-14 or enzymatic detection,15-17 small-molecule biocapture strategies provide gateways to new sensing opportunities.18 Immobilization of large biomolecules on surfaces requires avoiding denaturation upon surface adsorption and favorable orientation for ligand binding.19-24 In contrast, surface tethering of smallmolecule probes necessitates judicious selection of coupling chemistries and surface dilution to facilitate recognition by large biomolecule binding partners.22,25-32 For instance, the areal size mismatch on surfaces between small-molecule neurotransmitters or amino acids and large antibody or receptor binding partners is >100 fold.33,34 An important goal of small-molecule chemical patterning is site-specific placement of multiple probes on substrates for the interrogation of target binding specificity and selectivity.32,35-38 However, achieving this objective has been challenging.39-43 We developed additive methods to pattern small molecules to investigate biomolecule capture via relative quantification of binding on functionalized vs. unfunctionalized regions of substrates. Microcontact
insertion
neurotransmitters
and
printing precursors
(µCIP)
was
mimicking
used
to
endogenous
pattern
small-molecule
neurotransmitters
on
alkanethiol self-assembled monolayer (SAM)-modified Au substrates.44-46 Using this approach, molecular tethers are inserted into pre-formed SAMs and tethers are
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functionalized on-substrate with small-molecule probes. To circumvent problems associated with the sequential surface functionalization chemistries needed for multifunctionalized substrates, we used microfluidics to generate multiplexed substrates.38 Here, two-component SAMs with low proportions of tether molecules (
