Ultrasensitive protein detection: a case for microfluidic magnetic bead-based assays

Abstract

We review the use of magnetic micro- and nanoparticles ('magnetic beads') in microfluidic systems for ultrasensitive protein detection. During recent years magnetic beads have been used frequently in immunoassays, either as mobile substrates on which the target antigen is captured, as detection labels, or simultaneously as substrates and labels. The major part of the reviewed work has as application the detection of antibodies or disease biomarkers in serum or of biotoxins from food samples. Several of the most sensitive assays allow protein detection down to fg mL(-1) concentrations. We benchmark the performance of these microfluidic magnetic bead-based assays with the most promising earlier work and with alternative solutions.

Surface enhanced Raman spectroscopy (SERS) for in vitro diagnostic testing at the point of care

“…These are easy to manipulate with small permanent neodymium magnets held at the side of a vial, well plates, capillary tube, microfluidic channels, or even inside cells [162]. When functionalized with sensing ligands, this allows for faster, more automated washing steps while also preventing sample sedimentation often seen with repeated centrifugation [29,163]. Magnetic nanoparticles can also provide a plasmonic response when coated in gold or silver [164], therefore improving SERS enhancement capabilities [165][166][167].…”

“…It is defined as a group of metabolic diseases where ultimately the body's pancreas does not produce enough insulin or does not properly respond to insulin produced, resulting in high blood sugar levels over a prolonged period. Glucose meters and other POC devices utilize an assortment of methods for detecting and monitoring biomarkers including electrochemical [16][17][18][19][20], magnetic [21][22][23][24][25][26][27][28][29][30], optical [31][32][33][34], label-free spectroscopic analysis [35][36][37][38][39][40][41][42][43], colorimetric [44][45][46][47][48][49], and plasmonic nanoparticle based sensors [50][51][52]. Generally, electrochemical detection uses potentiometric, amperometric, and impedimetric measurements in conjunction with electroactive tags or free flowing electroactive analytes [17][18][19][20] [15,53,54] are examples of electrochemical and colorimet...…”

Magnetic micro/nanoparticle flocculation-based signal amplification for biosensing

“…In these applications, a secondary nonmagnetic label coated with biomolecules, such as antibody or deoxyribonucleic acid (DNA), binds to either target molecule or the magnetic bead and provides signal or signal amplification for the measurements. 28 However, dependency on biomolecular binding for signal amplification has some drawbacks. First of all, biomolecular binding events are sensitive to environmental conditions, such as temperature and ion concentrations of the medium.…”

Magnetic Particle-Scanning for Ultrasensitive Immunodetection On-Chip

“…First of all, both approaches of these so-called 'surface coverage' assays have resulted in an extremely low limit of detection. 20 However, by comparing the dose-response curves, obtained over similar ranges of concentrations for these two types of devices ('Ag on substrate' vs 'Ag on particles'), different behaviors have been observed.…”

“…[10][11][12][13][14][15][16][17][18] Functionalized superparamagnetic particles have been shown to be ideally suited for the rapid and efficient capture and isolation of target molecules. 19,20 Many of these magneto-microfluidic assays were based on a protocol, in which magnetic particles were immobilized in a flow and exposed to a series of sequential reagent exposure and washing steps, as inspired by a batch-type assay [21][22][23] , but also continuous flow microfluidic assays have been proposed, in which magnetic particles were moved through multilaminar reagent/washing solution flow streams to implement the assay protocol. 24 Also droplet-based systems have been proposed that allowed storage of reagent/washing solutions in aqueous droplets surrounded by an immiscible oil phase and employed magnetic particles that were moved between the different droplets to perform the assay protocol.…”