In order to have high sensitivity and specificity, the assay technology so-called immunomagnetic reduction (IMR) was developed in 2006. The reagent of IMR assay is composed of antibody functionalized magnetic Fe3O4 nanoparticles (diameter ~ 55 nm) dispersed in phosphate buffered saline. Once the magnetic nanoparticles bind with target biomarkers, the alternative-current (AC) magnetic susceptibility of reagent is reduced. Samples with ultra-low concentrated biomarkers show very tiny reductions in the AC magnetic susceptibility of reagent. An ultra-sensitive sensor is needed. High-temperature (high-Tc) superconducting quantum interference device (SQUID) magnetometer is a candidate to precisely sense tiny changes in magnetic signals. IMR analyzer utilizing a high-Tc SQUID magnetometer was developed in 2008. The IMR assay system including reagent and analyzer has been applied to quantitatively detect blood biomarkers, which concentrations are fg/ml - pg/ml, associated with Alzheimer’s disease (AD), Parkinson’s disease (PD) and frontotemporal dementia (FTD) since 2012. Up to now, there have been more than 80 papers of clinical evidence in Asian, American and Europe to demonstrate the feasibilities of using IMR system in clinics. The accuracy of finding early-stage AD, PD or FTD is higher than 80%. IMR system for assaying blood biomarkers of dementia were approved as an in-vitro medical device in Taiwan and Europe in 2020. It opens a new era to screen neurodegenerative diseases via blood draw instead of lumbar puncture. In this work, we would like to give an overview from the developments of IMR assay system to the clinical applications in assessing neurodegenerative diseases via assaying blood biomarkers.Correspondence: Charles S.Y. Yang (email: syyang@magqu.com)

Keywords:  immunomagnetic reduction, superconducting quantum interference device, biomarkers, neurodegenerative disease