Spectral image contrast-based flow digital nanoplasmon-metry for ultrasensitive antibody detection

Abstract

Background Gold nanoparticles (AuNPs) have been widely used in local surface plasmon resonance (LSPR) immunoassays for biomolecule sensing, which is primarily based on two conventional methods: absorption spectra analysis and colorimetry. The low figure of merit (FoM) of the LSPR and high-concentration AuNP requirement restrict their limit of detection (LOD), which is approximately ng to μg mL−1 in antibody detection if there is no other signal or analyte amplification. Improvements in sensitivity have been slow in recent for a long time, and pushing the boundary of the current LOD is a great challenge of current LSPR immunoassays in biosensing. Results In this work, we developed spectral image contrast-based flow digital nanoplasmon-metry (Flow DiNM) to push the LOD boundary. Comparing the scattering image brightness of AuNPs in two neighboring wavelength bands near the LSPR peak, the peak shift signal is strongly amplified and quickly detected. Introducing digital analysis, the Flow DiNM provides an ultrahigh signal-to-noise ratio and has a lower sample volume requirement. Compared to the conventional analog LSPR immunoassay, Flow DiNM for anti-BSA detection in pure samples has an LOD as low as 1 pg mL−1 within only a 15-min detection time and 500 μL sample volume. Antibody assays against spike proteins of SARS-CoV-2 in artificial saliva that contained various proteins were also conducted to validate the detection of Flow DiNM in complicated samples. Flow DiNM shows significant discrimination in detection with an LOD of 10 pg mL−1 and a broad dynamic detection range of five orders of magnitude. Conclusion Together with the quick readout time and simple operation, this work clearly demonstrated the high sensitivity and selectivity of the developed Flow DiNM in rapid antibody detection. Spectral image contrast and digital analysis further provide a new generation of LSPR immunoassay with AuNPs. Graphical Abstract

Nanomaterials‐based sensors for the detection of COVID‐19: A review

“…13 Thus, in the past couple of years, a lot of work has been conducted on rapidly detecting COVID‐19 using novel biosensors. 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 Likewise, many prominent researchers have spent a lot of time compiling several review articles about recent COVID diagnosis and treatment using different sensing strategies. 7 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 However, to the best of our knowledge, there is no systematic review article that extensively sums up the recent developments and research on nanomaterial‐based biosensors for rapid, sensitive, and selective detection of the SARS‐CoV‐2.…”

“…The National Institutes of Health strategic plan for COVID‐19 research calls for the need “to improve the basic understanding of SARS‐CoV‐2 and COVID 19 and develop the necessary tools and approaches to diagnose, prevent, and treat this disease,” highlighting the impetus on the rapid and reliable diagnosis of the coronavirus 13 . Thus, in the past couple of years, a lot of work has been conducted on rapidly detecting COVID‐19 using novel biosensors 14–21 . Likewise, many prominent researchers have spent a lot of time compiling several review articles about recent COVID diagnosis and treatment using different sensing strategies 7,22–30 .…”