Controlling Surface Wettability for Automated In Situ Array Synthesis and Direct Bioscreening

Abstract

The in situ synthesis of biomolecules on glass surfaces for direct bioscreening can be a powerful tool in the fields of pharmaceutical sciences, biomaterials, and chemical biology. However, it is still challenging to 1) achieve this conventional multistep combinatorial synthesis on glass surfaces with small feature sizes and high yields and 2) develop a surface which is compatible with solid‐phase syntheses, as well as the subsequent bioscreening. This work reports an amphiphilic coating of a glass surface on which small droplets of polar aprotic organic solvents can be deposited with an enhanced contact angle and inhibited motion to permit fully automated multiple rounds of the combinatorial synthesis of small‐molecule compounds and peptides. This amphiphilic coating can be switched into a hydrophilic network for protein‐ and cell‐based screening. Employing this in situ synthesis method, chemical space can be probed via array technology with unprecedented speed for various applications, such as lead discovery/optimization in medicinal chemistry and biomaterial development.

Automated Laser‐Transfer Synthesis of High‐Density Microarrays for Infectious Disease Screening

“…This correlation was also previously observed by others. [16] Moreover, to enable a fast analysis of thousands of fluorescent spots from various experiments (e.g., transfer parameters of 20 AAs), we developed an automated image detection software based on the open-source framework OpenCV. [30] Adv.…”

“…This high-throughput synthesis concept was introduced in the 1980s [5] and since continues to evolve. [6][7][8][9][10][11][12][13][14][15][16] The SPOT, [6] photolithographic, [7] and particle-based [10] syntheses are now commercialized [18][19][20] and commonly used to prepare peptides for binding studies. [21][22][23] However, each approach has at least one major drawback in regards to the peptide spot density, the possible peptide length, or the resulting peptide spot morphology (Table 1).…”

“…Coupling yield ≈95%, purification after cleavage possible ≈75% [17] ≈90% [10] ≈95% Compared to liquid solvent-based in situ microarray synthesis approaches [16,24] that require hydrophobic functionalization of the synthesis surface, the laser-based polymer transfer does not require this pre-treatment. Moreover, such technology is especially useful for rapidly generating individually customized arrays, which can aid diagnosis and monitoring of infectious [25] or autoimmune diseases [26] as rationally designed antigen variants can be quickly screened.…”

Robust and durable liquid-repellent surfaces

“…Wetting, referring to the process of making contact between a liquid and a solid (or liquid) surface, is a ubiquitous phenomenon that exists in our daily life, industry, agriculture, biology, etc., from raindrops on a car windshield to drastic shape transition of living tissues. [1][2][3][4][5][6][7][8] Wetting shows a range of curious, yet useful behaviors which make the fields concerned with their study intrinsically multidisciplinary, spanning across several areas of chemistry, biology, physics, engineering, etc. Since the introduction of Young's equation in 1805, 9 research on wetting and wettability has continued for over two hundred years.…”

“…, from raindrops on a car windshield to drastic shape transition of living tissues. 1–8 Wetting shows a range of curious, yet useful behaviors which make the fields concerned with their study intrinsically multidisciplinary, spanning across several areas of chemistry, biology, physics, engineering, etc. Since the introduction of Young's equation in 1805, 9 research on wetting and wettability has continued for over two hundred years.…”