(441a) Point of Need Biosensing of Protein Biomarkers from Complex Matrices

Biomarkers such as CEA, CA-19-9, CA-125, PSA, etc are currently quantified in diagnostic laboratories from body fluids to monitor progression, treatment and screening of various cancers, for which, point of need devices are not available. As with quantification of any protein from body fluids in a point of need (PON) format, the required low limit of detection for pg/ml determinations, interference form non-specifically (NSB) proteins present at many orders of magnitude larger concentrations, small sample size of a drop of blood vs venous draw, and long incubation times are challenges to be overcome by a PON platform. We present a PON sensor platform for quantification of biomarkers in body fluids using surface acoustic waves and nano-scale phenomena.

In our immunosensing approach, Rayleigh surface acoustic waves (SAWs) propagating in a delay-line SAW device are shown to be superior in replacing the current laboratory practice of extensive washing using buffer solutions to remove NSB interference. They are also shown to reduce incubation times by inducing acoustic streaming-based mixing of the sample, thus reducing assay times to minutes from hours/days. Guided SAWs with shear-horizontal polarization are shown to propagate in an orthogonal direction to the Rayleigh waves in certain piezoelectric substrates, which are effective in quantifying biomarkers in the liquid phase, leading to a compact device for simultaneous sensing, NSB removal and mixing. To lower the limits of detection to the pg/ml levels, we have explored nano-scale phenomena via gold nanoparticle (AuNP) based nanoprobes, and plasmonic enhancement of fluorescence to find the latter to be robust, albeit requiring additional optics to quantify fluorescence. We show that limits of detection are lowered by 2-3 orders of magnitude using these approaches. Multi-scale analysis of acoustic streaming, heat generation from streaming, and plasmonic enhancement of fluorescence have allowed us to both understand the fundamental phenomena and optimize the sensor device. We show that this orthogonal sensing device coupled with suitable electronics allows for constructing PON sensors for label-free, real-time sensing of biomarkers from complex fluids such as human plasma.