Biological small-molecule assays using gradient-based microfluidics

Biosens Bioelectron. 2021 Apr 15:178:113038. doi: 10.1016/j.bios.2021.113038. Epub 2021 Jan 27.

Abstract

Studying the potency of small-molecules on eukaryotic and prokaryotic cells using conventional biological settings requires time-consuming procedures and large volumes of expensive small-molecules. Microfluidics could significantly expedite these assays by enabling operation in high-throughput and (semi)automated modes. Here, we introduce a microfluidics platform based on multi-volume microchamber arrays that can produce a wide range of small-molecule concentrations with a desired gradient-based profile for rapid and precise biological testing within a single device with minimal hands-on time. The concept behind this device is based on introducing the same amount of a small-molecule into microchambers of different volumes to spontaneously generate a gradient concentration profile via diffusion. This design enables to obtain an unprecedented concentration range (e.g., three orders of magnitude) that can be easily adjusted, allowing us to pinpoint the precise effect of small-molecules on pre-loaded prokaryotic and eukaryotic cells. We also propose a comprehensive relationship for determining the loading time (the only required parameter for implementing this platform) in order to study the effects of any small-molecule on a biological species in a desired test. We demonstrate the versatility of this microfluidics platform by conducting two small-molecule assays-antimicrobial resistance and sugar-phosphate toxicity for both eukaryotic and prokaryotic biological systems.

Keywords: Antimicrobial susceptibility testing; Biological small-molecule; Biosensors; High-throughput biosensing; Microfluidics.

MeSH terms

  • Biological Assay
  • Biosensing Techniques*
  • Microfluidics*