High‐Throughput Drug Screening: A Microfabricated Sandwiching Assay for Nanoliter and High‐Throughput Biomarker Screening (Small 15/2019)

Abstract

In article number https://doi.org/10.1002/smll.201900300, Junmin Lee, Ali Khademhosseini, and co‐workers develop a nanoliter and high‐throughput drug screening platform based on the combination of microwell arrays as a cell culture substrate, and micropillar arrays for drug delivery and biomolecular detection in response to drugs. The developed platform requires only a small amount of sample volume from a few cells and demonstrates increasing control and throughput while allowing direct and real‐time on‐chip measurements. It is expected to aid in improving drug screening on patient biopsies from solid tumors to realize personalized cancer therapy.

Double-Sided Microwells with a Stepped Through-Hole Membrane for High-Throughput Microbial Assays

“…Cross-contamination-free methods to manipulate the chemical environment of massively arrayed microwells can significantly improve especially microwell-based drug screening and sequencing assay. In recent microwell-based drug screening, a microstructured stamp has been used to inject various concentrations and compositions of chemicals into the microwell array. , However, the plane-to-plane mechanical alignment process requires a very expensive and delicate five-axis micromanipulator such as a photolithography mask aligner at the reduced interdistance and diameter of the microwells, which means that a significant reliability issue occurs when throughput is increased with a limited budget on the alignment setup. The plane-to-plane alignment for our chip size by hand caused 7 serious misalignments among 10 trials, based on our empirical results.…”

“…Microchannels are an alternative but lose the ease of accessibility to the samples. , Second, many biological assays require multiple manipulations of chemical environments such as changing the medium, adding barcoded-beads, injecting chemicals such as lysis buffers, genetic inducers, or drugs, and washing with fresh medium . However, manipulation without cross-talk has relied on the five-axis plane-to-plane alignment of external microstructures, which becomes more error-prone, cumbersome, and expensive in proportion to the density of the bioreactors. − Third, microscale extraction methods are lacking in automation and isolation of intact cells. Capillary extraction processes require skillful handling and suffer from rapid evaporation during transport of nanoliter aqueous samples. , Although optical extraction methods have enabled simple automation, lights or heat may result in unfavorable effects to cells. , …”