Whole-Blood Boundary Analysis of BioFET-Based ctDNA Detection for Intravascular Sensing in Intrabody Nanonetworks

2026-05-21

AI Summary

This study addresses the challenge of reliably detecting low-concentration circulating tumor DNA (ctDNA) in whole blood using BioFET nanosensors. The authors present the first reduced-order stochastic simulation model that integrates charge-gating mechanisms, Debye screening theory, and biosensing noise. Employing Monte Carlo methods, they systematically evaluate the impact of operating point selection, non-specific adsorption, background fluctuations, and electronic noise. The work establishes a boundary analysis framework for ctDNA detection with BioFETs in whole blood, revealing that the short Debye length and nanoscale charge-to-channel separation drastically attenuate current response, while low-frequency noise and background variability compress discrimination margins, rendering low-abundance ctDNA undetectable. These insights provide critical theoretical foundations for designing high-sensitivity BioFET sensors.

Abstract

Liquid biopsy can detect tumor-derived biomarkers such as circulating tumor DNA (ctDNA), but ultra-low-fraction assays remain costly, slow, and difficult to scale. This motivates interest in intravascular in vivo sensing in the context of intrabody nanonetworks, where nanosensors could support local biomarker monitoring. BioFET-based nanosensors are relevant here because they are label-free, highly miniaturizable, and have shown strong ctDNA sensitivity in controlled media. We examine whether this sensitivity still yields reliable ctDNA detection in whole blood using a reduced-order stochastic simulation model that links operating-point selection, Debye-screened charge transduction, stochastic finite-capacity binding, nonspecific adsorption, background fluctuations, and intrinsic electronic noise to blank-threshold detection. Monte Carlo evaluation with physiologically grounded parameters shows that short Debye length and several-nanometer charge-to-channel separation attenuate the current shift, while low-frequency noise and background fluctuations reduce the margin between target-present and blank responses. Under the tested quasi-static charge-gating regime, the simulated current shifts do not reliably exceed the blank-derived threshold at low ctDNA concentrations. The model therefore provides a whole-blood boundary analysis that identifies which interface configurations and operating conditions most strongly limit reliable BioFET-based intravascular ctDNA detection.

Problem

• BioFET
• ctDNA detection
• intravascular sensing
• whole-blood
• intrabody nanonetworks

Innovation

• BioFET
• ctDNA detection
• intravascular sensing
• Debye screening
• stochastic modeling