Full On-Chip Nanoliter Immunoassay by Geometrical Magnetic Trapping of Nanoparticle Chains

Abstract

We propose an original concept to perform a complete on-chip sandwich immunoassay on magnetic nanoparticles that are self-assembled in chains in a uniform magnetic field. The magnetic chains are retained over periodically enlarged cross sections of a microfluidic channel. Thereby they strongly interact with the flow and rapidly capture the total of a low number of target molecules from nanoliter sample volumes. As an example, we demonstrate the detection of murine monoclonal antibodies in a noncompetitive sandwich immunoassay with a detection limit of 1 ng mL(-1) in nanoliters of hybridoma cell culture medium.

Microfluidic Chips for Point‐of‐Care Immunodiagnostics

“…[ 222 ] Magnetic beads are retained in self-assembled chains in microchannels with varying cross-sections in the presence of a homogenous perpendicular magnetic fi eld facilitating more effi cient mixing and enhanced antibody-antigen interaction. [ 223 ] Assays and sequencing experiments can be performed with sequential liquid fl ows. Beads are assemblies of receptors that can increase the number of binding site in a given volume compared to detection regions on surfaces.…”

Bubble cell for magnetic bead trapping in capillary electrophoresis

“…a wide range of applications, such as, magnetic transport, labels for detection, mixing, cell manipulation and separation, DNA purification, catalysis, or on-chip DNA electrophoresis [13]. As previously introduced, they were also used as a solid phase to perform protein immunocapture [14] and epitope mapping of allergens [15], on-line preconcentration of lowdensity lipoproteins [16], and in-line extraction with octadecylsilane-functionalized beads [17], on-chip enzymatic digestion [18,19], and immunoassays [20][21][22][23][24][25][26].…”

Magnetic track array for efficient bead capture in microchannels

“…Whereas the magnetic beads are nowadays commonly used at laboratory-scale (i.e., in tube), the development of methodologies in microfluidic format has recently emerged decreasing sample/reagent consumption, cost and time consumption [14][15][16][17]. Such magnetism-based devices have found great applications in biology, as for cell manipulation [18][19][20][21][22][23], (bio)chemical reaction as proteolysis [24,25], bioassay [26][27][28], DNA or RNA hybridization [29,30]. Magnetic beads appeared as well in microsystems to design mixers, valves, or switches [31][32][33][34][35][36][37].…”

“…However, the complex microfabrication processes and the limited field strength (0-100 mT) are the weak points of these devices. In contrast, passive magnetic microsystems use external macro-sized permanent magnets or electromagnets [25,27,38]. The process is simplified and larger magnetic fields (>0.5 T) and forces can be reached.…”