Ultra-sensitive protein detection via Single Molecule Arrays towards early stage cancer monitoring

Stephanie M Schubert,Rachel J Buchsbaum,Wenhui Zhou,Shazia Baig,Stephanie R Walter,Charlotte Kuperwasser,David R Walt,Lisa M Arendt

doi:10.1038/srep11034

Abstract

The early diagnosis of cancers and continued monitoring of tumor growth would be greatly facilitated by the development of a blood-based, non-invasive, screening technique for early cancer detection. Current technologies for cancer screening and detection typically rely on imaging techniques or blood tests that are not accurate or sensitive enough to definitively diagnose cancer at its earliest stages or predict biologic outcomes. By utilizing Single Molecule Arrays (SiMoA), an ultra-sensitive enzyme-linked immunosorbent assay (ELISA) technique, we were able to measure increasing levels of prostate specific antigen (PSA) within murine serum over time, which we attribute to tumor development. The measured concentrations of PSA were well below the detectable limits of both a leading clinical diagnostic PSA ELISA assay as well as a commercial ultra-sensitive PSA assay. Our work benchmarks the role of SiMoA as a vital tool in monitoring previously non-detectable protein biomarkers in serum for early cancer detection and offers significant potential as a non-invasive platform for the monitoring of early stage cancer.

Highlights

Is comparable to previous SiMoA work[9]
This work describes a proof-of-concept study where prostate cancer was induced in a mouse model at very low cell inoculums to demonstrate the utility of SiMoA as an early cancer detection tool
Increasing levels of prostate specific antigen (PSA) were measured in the serum of mice as a sign of tumor progression, since the only source of increasing levels of secreted human PSA in the mouse model is the proliferation of the PSA-secreting cancer cells

Summary

Introduction

Other literature reports have demonstrated sensitive PSA tests, including recent work by Liu et al where they utilized gold nanoparticles to create a colorimetric ultra-sensitive assay for PSA with a LOD of 0.0031 pg/mL12. Notable works have utilized electrochemical microfluidic arrays[13], electrochemical immunosensors with gold nanoparticles functionalized with magnetic multi-walled carbon nanotubes[14], and novel laser-induced fluorescence systems[15] to detect cancer biomarkers. These reports advanced the field of ultra-sensitive biomarker detection, many of them require complicated assay set-ups, lengthy preparation, or are potentially subject to sensor fouling. This work is demonstrated with PSA, it should be applicable to any biomarker associated with tumor growth that is found in the blood

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Conclusion