Microfluidic Production of Autofluorescent BSA Hydrogel Microspheres and Their Sequential Trapping for Fluorescence-Based On-Chip Permanganate Sensing

Abstract

Microfabrication technologies have extensively advanced over the past decades, realizing a variety of well-designed compact devices for material synthesis, separation, analysis, monitoring, sensing, and so on. The performance of such devices has been undoubtedly improved, while it is still challenging to build up a platform by rationally combining multiple processes toward practical demands which become more diverse and complicated. Here, we present a simple and effective microfluidic system to produce and immobilize a well-defined functional material for on-chip permanganate (MnO4−) sensing. A droplet-based microfluidic approach that can continuously produce monodispersed droplets in a water-in-oil system is employed to prepare highly uniform microspheres (average size: 102 μm, coefficient of variation: 3.7%) composed of bovine serum albumin (BSA) hydrogel with autofluorescence properties in the presence of glutaraldehyde (GA). Each BSA hydrogel microsphere is subsequently immobilized in a microchannel with a hydrodynamic trapping structure to serve as an independent fluorescence unit. Various anions such as Cl−, NO3−, PO43−, Br−, BrO3−, ClO4−, SCN−, HCO3−, and MnO4− are individually flowed into the microchannel, resulting in significant fluorescence quenching only in the case of MnO4−. Linear correlation is confirmed at an MnO4− concentration from 20 to 80 μM, and a limit of detection is estimated to be 1.7 μM. Furthermore, we demonstrate the simultaneous immobilization of two kinds of different microspheres in parallel microchannels, pure BSA hydrogel microspheres and BSA hydrogel microspheres containing rhodamine B molecules, making it possible to acquire two fluorescence signals (green and yellow). The present microfluidics-based combined approach will be useful to record a fingerprint of complicated samples for sensing/identification purposes by flexibly designing the size and composition of the BSA hydrogel microspheres, immobilizing them in a desired manner and obtaining a specific pattern.

Preparation of Heat-Denatured Macroaggregated Albumin for Biomedical Applications Using a Microfluidics Platform

“…Microfluidics offers an attractive approach to prepare microparticles in a more controlled fashion, as has been demonstrated for many different types of materials . There are several recent descriptions on how to make (drug-loaded) albumin nanoparticles − and microparticles − with microfluidic methods. The microparticles in these reports were stabilized via chemical cross-linking, either by introducing a fixative directly into the albumin-containing droplets formed within the chip or off-chip in a stirred vessel. , Heat has also been reported to stabilize microparticles prepared on a microfluidic device, albeit with proteins other than albumin.…”

“…There are several recent descriptions on how to make (drug-loaded) albumin nanoparticles − and microparticles − with microfluidic methods. The microparticles in these reports were stabilized via chemical cross-linking, either by introducing a fixative directly into the albumin-containing droplets formed within the chip or off-chip in a stirred vessel. , Heat has also been reported to stabilize microparticles prepared on a microfluidic device, albeit with proteins other than albumin. For example, whey microparticles were cured off-chip within a heated stirred vessel, while egg emulsion droplets were “cooked” in situ using a heated capillary microfluidic system .…”

Injectable, Adhesive Albumin Nanoparticle-Incorporated Hydrogel for Sustained Localized Drug Delivery and Efficient Tumor Treatment

“…As readily accessible natural materials, albumins, including BSA, HSA, and recombinant human serum albumin, have shown potential as building blocks for hydrogels owing to their water-solubility, stability, biodegradability, ease of modification, low immunogenicity, and nontoxicity . However, existing albumin-based hydrogels are usually fabricated via cross-linking approaches involving toxic substances, such as glutaraldehyde, − iron mental, , and photoinitiators, − which can cause safety concerns in their further biomedical application.…”

Static droplet array for the synthesis of nonspherical microparticles

“…[25], both the generation of droplets and the capture of upstream droplets were realized in SDA. Considering the features of no waste generation and in suit capture of droplets, SDA has been widely used in single‐cell analysis [26, 27], cell culture [28], and molecule detection [29, 30]. For example, in the SDA chip proposed by Warkiani et al.…”

“…In the following study by Boukellal et al [25], both the generation of droplets and the capture of upstream droplets were realized in SDA. Considering the features of no waste generation and in suit capture of droplets, SDA has been widely used in single-cell analysis [26,27], cell culture [28], and molecule detection [29,30]. For example, in the SDA chip proposed by Warkiani et al [26], both the single-cell culture and the real-time tracking of matrix metalloproteinase activity of MDA-MB-231 cells were realized.…”