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๐—ฃ๐—ฎ๐˜๐˜๐—ฒ๐—ฟ๐—ป๐—ถ๐—ป๐—ด ๐—ฝ๐—ฟ๐—ผ๐˜๐—ฒ๐—ถ๐—ป๐˜€ ๐˜„๐—ถ๐˜๐—ต ๐—น๐—ฎ๐˜€๐—ฒ๐—ฟ-๐—ด๐—ฟ๐—ผ๐˜„๐—ป ๐—บ๐—ถ๐—ฐ๐—ฟ๐—ผ-๐—ฏ๐˜‚๐—ฏ๐—ฏ๐—น๐—ฒ๐˜€: ๐—ฎ ๐—ฝ๐—ผ๐˜€๐˜€๐—ถ๐—ฏ๐—น๐—ฒ ๐—ป๐—ฒ๐˜„ ๐—ฟ๐—ผ๐˜‚๐˜๐—ฒ ๐˜๐—ผ๐˜„๐—ฎ๐—ฟ๐—ฑ๐˜€ ๐—น๐—ผ๐˜„-๐—ฐ๐—ผ๐˜€๐˜ ๐—ฑ๐—ถ๐—ฎ๐—ด๐—ป๐—ผ๐˜€๐˜๐—ถ๐—ฐ๐˜€ ๐—ฎ๐—ป๐—ฑ ๐—ฏ๐—ถ๐—ผ๐˜€๐—ฒ๐—ป๐˜€๐—ถ๐—ป๐—ด

Patterning biomolecules (including proteins such as antigens and antibodies) in pre-designed, parallel architectures can be a game-changer in rapid, inexpensive diagnostics. However, typical patterning methodologies, including top-down approaches such as photolithography and e-beam lithography, or bottom-up approaches such as solgel nanofabrication, molecular self-assembly, and DNA-scaffolding - all have limitations in efficacy for various reasons ranging from damaging the biospecimens to being slow and inflexible.

In this context, Microbubble lithography (MBL) is a comparatively recent (about a decade-old) micro-patterning method that uses laser-generated and translated microbubbles to self-assemble and pattern materials of choice in real time. Thus, MBL has been used to pattern diverse mesoscopic organic and inorganic materials, allowing for various applications including the fabrication of plastic electronics, catalytic chips, and even biosensing. However, in spite of its success in patterning mesoscopic entities, MBL has not yet been employed in developing continuous patterns of living organisms. This is primarily due to the high temperatures associated with a bubble nucleated due to heat generated by tightly focusing a laser โ€“ which is at the heart of this technique.

In this paper, we report the successful creation of a strategy for immobilizing diverse biospecimens on transparent substrates using MBL. Thus, we develop a heterostructured platform made up of a scaffold to form microbubbles, a crosslinker to facilitate adherence, and finally the concerned immobilized biospecimen. Our deployment of fast laser translation speeds ensures no temperature-induced damage to the biospecimens since their contact time with the microbubbles is less than a hundred milliseconds. Our patterned biospecimens cover a wide range of biological macromolecules, such as reporter proteins, bacterial samples, and viruses at varying concentrations. Most importantly, we also performed experiments to determine the activity of the biospecimens, especially bacterial species and virus strains, post patterning โ€“ and obtained conclusive evidence of them retaining their vegetative activity.

Overall, this study sets the groundwork for manufacturing multilayer heterostructures of living matter using MBL, and may open a new paradigm in designing bioelectronic chips, and in fast, inexpensive, and even parallelized biosensing and diagnostics of pathogens, leveraging and highlighting the ubiquitous nature of MBL in terms of patterning โ€˜everything mesoscopicโ€™.

Article details:

Title: Biologically Active Micropatterns of Biomolecules and Living Matter Using Microbubble Lithography

Authors: Anand Dev Ranjan, Sucharita Bhowmick, Arnab Gupta, Amirul Islam Mallick, Ayan Banerjee



#Research Highlight

Posted on: July 12th, 2024