Magnetic bioassay system progresses toward versatile device for rapid point-of-care diagnosis

A prototype tabletop bioassay system has achieved a limit of detection of 0.2 attomole, comparable to — but more complex and labor-intensive than — state-of-the-art enzyme-linked immunosorbent assays (ELISA) used to detect viruses and other pathogens. The new system integrates a microfluidic sample handler, magnetic nanoparticle (MNP) probes, and an ultrasensitive high-temperature superconducting quantum interference device (SQUID) to do the same job, but at a fraction of the time.

The achievement, reported in APL Bioengineering, advances Sweden’s ambitious Project FLU-ID toward its goal: a compact and versatile portable diagnostics unit for rapid detection of influenza at the point of care. While many rapid tests exist, they are beset by variable sensitivity and, in the case of influenza, often fail to distinguish virus subtypes, a critical step for vaccine development.

The team’s prototype exploits rolling circle amplification, a method to generate long strands of nucleic acid sequences that collapse into coils, a process that is initiated only when the target DNA or RNA strands are present in the test sample. The coils bind to oligonucleotide-functionalized MNPs, dramatically increasing their hydrodynamic volume and allowing for a high sensitivity SQUID read-out of changes in Brownian motion of the volume-amplified MNPs in the magnetic bioassay.

The authors tested their enhanced approach on synthetic Vibrio cholera DNA. Using the superconducting SQUID sensor, they made measurements of the oligonucleotide-functionalized MNPs to determine their reference Brownian relaxation peak frequencies. After the V. cholera DNA target was added and amplified, a fraction of the MNPs were immobilized via attachment to the DNA coils. The AC susceptibility amplitude at the Brownian relaxation frequency then decreased significantly, yielding tell-tale evidence of the pathogen’s presence within two hours.

Source: “Volume-amplified magnetic bioassay integrated with microfluidic sample handling and high-T_c SQUID magnetic readout,” by Sobhan Sepehri, Emil Eriksson, Alexei Kalaboukhov, Teresa Zardán Gómez de la Torre, Kiryl Kustanovich, Aldo Jesorka, Justin F. Schneiderman, Jakob Blomgren, Christer Johansson, Maria Strømme, and Dag Winkler, APL Bioengineering (2017). The article can be accessed at https://doi.org/10.1063/1.4999713 .