Aptamer selection via versatile microfluidic platforms and their diverse applications

Aptamers are synthetic oligonucleotides that bind with high affinity and specificity to various targets, making them invaluable for diagnostics, therapeutics, and biosensing. Microfluidic platforms can improve the efficiency and scalability of aptamer selection, especially through advancements in systematic evolution of ligands by exponential enrichment (SELEX) methods. Microfluidic SELEX methods are less time-consuming and labor-intensive and include critical steps like library preparation, binding, partitioning, and amplification. This review examines the contributions of microfluidic technology to SELEX-based aptamer identification, with alternative methods like conditional SELEX, in vivo-like SELEX and Non-SELEX for selecting aptamers and also discusses critical SELEX steps over the past decade. This work also examined the integrated microfluidic systems for SELEX, highlighting innovations such as conditional SELEX and in vivo-like SELEX. These advancements provide potential solutions to existing challenges in aptamer selection using conventional SELEX, especially concerning biological samples. A trend toward non-SELEX methods was also reviewed and discussed, wherein nucleic acid amplification was eliminated to improve aptamer selection. Microfluidic platforms have demonstrated versatility not only in aptamer selection but also in various detection applications; they allow for precise control of liquid flow and have been essential in the advancement of therapeutic aptamers, facilitating accurate screening, enhancing drug delivery systems, and enabling targeted therapeutic interventions. Although advances in microfluidic technology are expected to enhance aptamer-based diagnostics, therapeutics, and biosensing, challenges still persist, especially in up-scaling microfluidic systems for various clinical applications. The advantages and limitations of integrating microfluidic platforms with aptamer development are further addressed, emphasizing areas for future research. We also present a perspective on the future of microfluidic systems and aptamer technologies, highlighting their increasing significance in healthcare and diagnostics.