Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Single Droplet Microsensor for Ultra-Short Circulating EFGR Mutations Detection in Lung Cancer Based on Multiplex EFIRM Liquid Biopsy

Fang Wei, and Peter Yu contributed equally to this work.
Version 1 : Received: 5 May 2023 / Approved: 6 May 2023 / Online: 6 May 2023 (09:44:49 CEST)

A peer-reviewed article of this Preprint also exists.

Wei, F.; Yu, P.; Cheng, J.; Li, F.; Chia, D.; Wong, D.T.W. Single-Droplet Microsensor for Ultra-Short Circulating EFGR Mutation Detection in Lung Cancer Based on Multiplex EFIRM Liquid Biopsy. Int. J. Mol. Sci. 2023, 24, 10387. Wei, F.; Yu, P.; Cheng, J.; Li, F.; Chia, D.; Wong, D.T.W. Single-Droplet Microsensor for Ultra-Short Circulating EFGR Mutation Detection in Lung Cancer Based on Multiplex EFIRM Liquid Biopsy. Int. J. Mol. Sci. 2023, 24, 10387.

Abstract

Liquid biopsy is a rapidly emerging field which involves the minimal/non-invasive assessment of signature somatic mutations through analysis of circulating tumor DNA (ctDNA) shed by tumor cells in bodily fluids. The broad, unmet need for liquid biopsy lung cancer detection is the lack of multiplex platform that can detect a mutation panel of lung cancer genes using minimum amount of sample, especially for ultra-short ctDNA (usctDNA). Here we developed a non-PCR and non-NGS-based single droplet based multiplexing microsensor technology “Electric Field-Induced Released and Measurement (EFIRM) Liquid Biopsy” (m-eLB) for lung can-cer-associated usctDNA. The m-eLB provides multiplexable assessment of usctDNA within a single droplet of biofluid in only one well of micro-electrodes, as each electrode coated with dif-ferent probes for the ctDNA. In this m-eLB prototype, it demonstrates accuracy for 3 tyrosine ki-nase inhibitor related EGFR target sequences in synthetic nucleotides. The accuracy for the multi-plexing assay has an AUC of 0.98 for L858R, Ex19del, AUC of 0.94 for Ex19 deletion and AUC of 0.93 for T790M. By combining the 3 EGFR assay together, the AUC was 0.97 for the multiplexing assay.

Keywords

Biosensors; ultra-short circulating tumor DNA; Lung Cancer; Liquid biopsy; EGFR

Subject

Biology and Life Sciences, Biology and Biotechnology

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