Massively Multiplexed Tip-Based Photochemical Lithography under Continuous Capillary Flow

Carlos Carbonell, Daniel J. Valles, Alexa M. Wong, Mei Wai Tsui, Moussa Niang, Adam B. Braunschweig

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Multiplexed microarrays—where different biological probes are spatially encoded onto a surface into spots with micrometer-scale diameters—have facilitated the rapid advancement of “omics” research. Further miniaturization of feature diameters could increase the number of probes in a microarray, reduce the sample required for analysis, and decrease costs. Tip-based lithography (TBL) has gained popularity for patterning delicate, biologically active materials, but no versatile TBL-based multiplexing strategy has been devised. Here, we combine microfluidics, beam pen lithography, and photochemical surface reactions to create multiplexed arrays. For proof of concept, the thiol-ene reaction was optimized, and the reaction kinetics were analyzed. Subsequently, we created several patterns containing multiple fluorescent alkenes, where each pattern was designed to demonstrate a different capability of this instrument. This patterning strategy is a powerful approach to studying and optimizing organic reactions on surfaces and creating massively multiplexed arrays and, as such, could provide an entirely new approach for miniaturizing biochips or understanding interfacial reactivity. There is a pressing desire to reduce feature diameters in biological arrays, which would increase the number of probes on the surface and reduce the sample volume required for analysis. The challenge that precludes miniaturization in biochips is that most nanolithography methods require high-energy beams that would denature or destroy soft matter. Alternatively, tip-based lithography (TBL) uses arrays of nanoscopic tips to pattern reagents on a surface nondestructively, but no versatile multiplexing strategy has been developed. Here, we solve this long-standing problem in TBL by combining massively parallel beam pen arrays, microfluidics, and organic surface chemistry to create multiplexed arrays whose features have a diameter of ∼1 μm. The applications of this printing platform include the preparation of gene, protein, and glycan chips that can rapidly advance “omics” research as well as provide a new tool for probing interfacial reactivity. Braunschweig and co-workers developed a printing tool that combines microfluidics, organic photochemistry, and massively parallel tip-based lithography. This instrument can create complex multiplexed patterns with ∼1 μm resolution or be used for rapidly determining the kinetics of organic reactions at interfaces. This flexible printing strategy could lead to the rapid advancement of “omics” research.

Original languageEnglish (US)
Pages (from-to)857-867
Number of pages11
Issue number4
StatePublished - Apr 12 2018


  • click chemistry
  • continuous flow
  • dip-pen nanolithography
  • microarrays
  • microfluidics
  • nanolithography
  • photochemistry
  • surface kinetics

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry
  • Environmental Chemistry
  • Chemical Engineering(all)
  • Biochemistry, medical
  • Materials Chemistry


Dive into the research topics of 'Massively Multiplexed Tip-Based Photochemical Lithography under Continuous Capillary Flow'. Together they form a unique fingerprint.

Cite this