Time-encoded electrical detection of trace RNA biomarker by integrating programmable molecular amplifier on chip

Area of Science:

• Biotechnology
• Nanotechnology
• Molecular Diagnostics

Background:

• Point-of-care (PoC) molecular diagnostics face challenges in detecting low-concentration biomarkers due to non-specific binding and inefficient mass transport.
• Existing platforms struggle with sensitivity and reliability for clinical applications, especially with complex biological samples.

Purpose of the Study:

• To develop a novel PoC biosensor overcoming limitations in low-biomarker detection.
• To enhance signal transduction through a combination of nanoscale field-effect transistors and molecular programming for amplified detection.

Main Methods:

• Utilized wafer-scale fabricated nanoscale biologically-sensitive field-effect transistor arrays (BioFET-arrays) as sensitive transducers.
• Implemented a programmable universal molecular amplifier (PUMA) system for biomarker-triggered amplification and signal generation.
• Employed a time-domain electrical signal analysis of PUMA activity instead of traditional threshold shift measurements.

Main Results:

• Achieved a limit of detection (LoD) as low as 10 fM for the miRNA biomarker LET7a.
• Demonstrated wide dynamic ranges from 10 pM to 10 nM in complex physiological solutions.
• Showcased reusability of the biosensor platform for over three uses, indicating cost-effectiveness.

Conclusions:

• The developed PoC biosensor effectively addresses challenges in low-biomarker detection through an integrated BioFET and PUMA system.
• The novel detection strategy offers high sensitivity, broad dynamic range, and potential for cost-effective, reusable diagnostic tools.
• This approach circumvents direct biomarker hybridization at the transducer, enhancing platform longevity and reliability.