An aptamer-based magnetic flow cytometer using matched filtering

Abstract

Facing unprecedented population-ageing, the management of noncommunicable diseases (NCDs) urgently needs a point-of-care (PoC) testing infrastructure. Magnetic flow cytometers are one such solution for rapid cancer cellular detection in a PoC setting. In this work, we report a giant magnetoresistive spin-valve (GMR SV) biosensor array with a multi-stripe sensor geometry and matched filtering to improve detection accuracy without compromising throughput. The carefully designed sensor geometry generates a characteristic signature when cells labeled with magnetic nanoparticles (MNPs) pass by thus enabling multi-parametric measurement like optical flow cytometers (FCMs). Enumeration and multi-parametric information were successfully measured across two decades of throughput. 10-µm polymer microspheres were used as a biomimetic model where MNPs and MNP-decorated polymer conjugates were flown over the GMR SV sensor array and detected with a signal-to-noise ratio (SNR) as low as 2.5 dB due to the processing gain afforded by the matched filtering. The performance was compared against optical observation, exhibiting a 92% detection efficiency. The system achieved a 95% counting accuracy for biomimetic models and 98% for aptamer-based pancreatic cancer cell detection. This system demonstrates the ability to perform reliable PoC diagnostics towards the benefit for NCD control plans.

Hitting the diagnostic sweet spot: Point-of-care SARS-CoV-2 salivary antigen testing with an off-the-shelf glucometer

“…The choice of saliva as a target specimen for testing presents challenges and opportunities. Saliva is the most readily obtained human specimen; however, it is also a complex and viscous sample consisting of various electrolytes, enzymes, and antibodies 38,39 posing hurdles for specific and interference-free biomarker detection 40 . This is reflected in our data, where we found a higher LOD for protein spiked in saliva as compared to buffer, likely a consequence of the viscosity and proteases found in saliva.…”

“…Aptamers are oligonucleotide (DNA or RNA) ligands that are selected through an iterative process known as SELEX 42,43 . They share similar affinity and specificity to monoclonal antibodies, yet can be mass produced at low cost, are stable at ambient temperatures for long-term storage, and can be chemically modified and engineered to produce conformational switches [44][45][46] . Specifically, the amount of overlap between the aptatope and the antisense strand in this assay allows the affinity to be engineered where it is intentionally designed to have low affinity for facile release when the viral protein is present.…”