Multiplex cell microarrays for high-throughput screening

Abstract

Microarray technology was developed in the early 1990s to measure the transcription levels of thousands of genes in parallel. The basic premise of high-density arraying has since been expanded to create cell microarrays. Cells on chip are powerful experimental tools for high-throughput and multiplex screening of samples or cellular functions. Miniaturization increases assay throughput while reducing both reagent consumption and cell population heterogeneity effect, making these systems attractive for a wide range of assays, from drug discovery to toxicology, stem cell research and therapy. It is usual to functionalize the surface of a substrate to design cell microarrays. One form of cell microarrays, the transfected cell microarray, wherein plasmid DNA or siRNA spotted on the surface of a substrate is reverse-transfected locally into adherent cells, has become a standard tool for parallel cell-based analysis. With the advent of technology, cells can also be directly spotted onto functionalized surfaces using robotic fluid-dispensing devices or printed directly on bio-ink material. We are providing herein an overview of the latest developments in optical cell microarrays allowing high-throughput and high-content analysis.

Microfluidic chambers using fluid walls for cell biology

“…Arrays with more wells and volumes down to a few femtoliters have been developed ( 2 , 3 ). Arrays of aqueous drops sitting on flat (usually patterned) surfaces and overlaid with an immiscible liquid to prevent evaporation have also been fabricated ( 4 – 9 ); in these, liquid walls/ceilings confine the aqueous phase. The burgeoning field of droplet-based microfluidics also uses fluid walls to confine liquids ( 10 – 12 ).…”

Effect of design geometry, exposure energy, cytophilic molecules, cell type and load in fabrication of single-cell arrays using micro-contact printing

“…The SCA technology described here opens for high-throughput studies of single cells on a scale barely thinkable a few decades ago. This technology is therefore a powerful tool for a variety of applications including, but not limited to, the testing of the effect of drugs, toxins or other external stimuli on cells 4 . Photolithography and soft lithography are often used for the fabrication of cellular arrays.…”

“…This heterogeneity may arise for a number of different reasons including improved population survival and functionality 2 , 3 . The study of population heterogeneity has therefore become a central topic within life sciences and resulted in several different approaches to obtain and study arrays of immobilised single cells 4 . These approaches are faced with multiple challenges such as they must permit simultaneous study of a high number of cells, provide resolution at the single-cell level while maintaining cell viability and function.…”

Robotic Cell Printing for Constructing Living Yeast Cell Microarrays in Microfluidic Chips

“…As cell collections grow, further miniaturization of cell assays is needed to increase parallelism of the analyses. Cell microarrays provide an attractive solution, as they could increase the throughput significantly [1][2][3]. A cellular microarray consists of a solid support wherein small volumes of different biomolecules and cells can be displayed in defined locations, allowing the multiplexed interrogation of living cells and the analysis of cellular responses [4,5].…”