Bio-Microarray Fabrication Techniques—A Review

Abstract

Microarrays with biomolecules (e.g., DNA and proteins), cells, and tissues immobilized on solid substrates are important tools for biological research, including genomics, proteomics, and cell analysis. In this paper, the current state of microarray fabrication is reviewed. According to spot formation techniques, methods are categorized as "contact printing" and "non-contact printing." Contact printing is a widely used technology, comprising methods such as contact pin printing and microstamping. These methods have many advantages, including reproducibility of printed spots and facile maintenance, as well as drawbacks, including low-throughput fabrication of arrays. Non-contact printing techniques are newer and more varied, comprising photochemistrybased methods, laser writing, electrospray deposition, and inkjet technologies. These technologies emerged from other applications and have the potential to increase microarray fabrication throughput; however, there are several challenges in applying them to microarray fabrication, including interference from satellite drops and biomolecule denaturization.

Analytical Devices Based on Direct Synthesis of DNA on Paper

“…[3] The standard method of fabrication for microarrays is pin-spotting-a method in which a robotic system deposits small volumes of a solution containing a probe (usually DNA, RNA, antibody, or protein) onto a glass, silicon, or polymer-based substrate. [4] Alternative methods include microstamping, inkjet printing, laser writing, or electrospray deposition, among others [5,6] . These substrates can be derivatized with poly-L-lysine, polyamidoamine dendrimer, amino-terminated silanes, aldehydes, carboxylic acids, or other reactive groups that facilitate attachment.…”

A robotics platform for automated batch fabrication of high density, microfluidics-based DNA microarrays, with applications to single cell, multiplex assays of secreted proteins

“…In terms of reproducibility, typical spot-to-spot coverage variation can be from 5%-10% across individual substrates, and 10%-30% between substrates. 11,12 These factors make spotted arrays useful for a host of biological assays; they provide a standard against which other molecular patterning techniques can be compared.…”

3D thermoplastic elastomer microfluidic devices for biological probe immobilization

“…1,2 DNA and protein microarrays, for example, offer the possibility to study concurrently the interaction between a target sample and a large number of probes, which makes them indispensible for many areas including drug discovery, 3,4 30 clinical diagnostic, 3,5 and gene sequencing. 6,7 However, microarrays still largely depend on detection techniques such as fluorescence labeling or surface plasmon resonance which are difficult to apply to point-of-care applications.…”

“…Also, the rapid and uncontrolled drying of liquid can lead to non-uniform spots and denaturation of sensitive material, especially when the dimensions of the spots are decreased below ~80 m. 1,22,23 Microfluidics provides a simple and convenient path to 60 control the immobilization conditions as well as the dimension, positioning, and uniformity of the deposited features. 18,19,[29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47] To this end, microfluidic immobilization devices typically consist of a network of channels patterned in poly(dimethylsiloxane) (PDMS), a thermoset elastomer that 65 can create reversible conformal sealing upon contact with a planar solid support.…”

“…18,19, Among these techniques, pin spotting has become the standard fabrication technology for DNA microarrays due to its relative simplicity and the possibility to 50 produce a vast number of spots in an automated fashion. 1,22 Pin spotting employs a set of metallic micropins to deliver minute amounts of liquid upon contact with a surface. However, accurate positioning and registration of the spots between each successive printing cycle are difficult to control 55 and require costly and sophisticated tools.…”