Hydrogel microparticles for biosensing

Abstract

Due to their hydrophilic, biocompatible, and highly tunable nature, hydrogel materials have attracted strong interest in the recent years for numerous biotechnological applications. In particular, their solution-like environment and non-fouling nature in complex biological samples render hydrogels as ideal substrates for biosensing applications. Hydrogel coatings, and later, gel dot surface microarrays, were successfully used in sensitive nucleic acid assays and immunoassays. More recently, new microfabrication techniques for synthesizing encoded particles from hydrogel materials have enabled the development of hydrogel-based suspension arrays. Lithography processes and droplet-based microfluidic techniques enable generation of libraries of particles with unique spectral or graphical codes, for multiplexed sensing in biological samples. In this review, we discuss the key questions arising when designing hydrogel particles dedicated to biosensing. How can the hydrogel material be engineered in order to tune its properties and immobilize bioprobes inside? What are the strategies to fabricate and encode gel particles, and how can particles be processed and decoded after the assay? Finally, we review the bioassays reported so far in the literature that have used hydrogel particle arrays and give an outlook of further developments of the field.

Smart Hydrogel Microfluidics for Single‐Cell Multiplexed Secretomic Analysis with High Sensitivity

“…Monodispersed hydrogel microbeads were fabricated using a cross‐junction droplet generation device (Figure S1, Supporting Information) prior to their functionalization with capture primary antibodies (IgGs). Covalent coupling enables the stable immobilization of the capture antibodies without the leaching problems typically associated with physical absorption approaches . For PNIPAM‐based gels, additional functional groups are required to perform covalent modifications.…”

“…The hydrated and nonrigid gel matrix also improved the target binding kinetics by reducing steric issues, potentially augmenting assay performances. However, more often than not, hydrogel‐based systems suffer from diffusion limitations, giving rise to large assay variabilities and reduced detection capabilities. Therefore, an interconnected pore structure with significantly large pores is crucial for allowing target proteins to diffuse freely through P (NIPAM‐ co ‐AAc) gels.…”

MRBLES 2.0: High-throughput generation of chemically functionalized spectrally and magnetically-encoded hydrogel beads using a simple single-layer microfluidic device

“…Recently developed spectrally encoded hydrogel beads provide an appealing alternative that have been used for a variety of biomedical and sensing applications 20,21 . Hydrogel beads are comprised of a cross-linked, hydrated polymeric network made up of one or more hydrophilic monomers, providing near fluid-phase kinetics at functionalized surfaces as well as high-efficiency molecular loading 22,23 , and microfluidic droplet generators have been used to produce and polymerize hydrogel beads at high-throughput 24 .…”

High‐Throughput Fabrication and Modular Assembly of 3D Heterogeneous Microscale Tissues

“…The assembly of cell‐encapsulating blocks with a defined 3D structure represents a promising approach to create a functional hetero‐architecture to mimic complex natural tissues. These approaches have a significant potential for microscale tissue engineering, personalized medicine screening, and drug delivery . In brief, these reported methods for fabricating 3D tissue structures can be classified into two categories: top‐down and bottom‐up.…”