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A Dual Amplification Photoelectrochemical Platform for KRAS Mutation Detection

Project description

A new way to detect cancer gene mutations

Detecting specific KRAS mutations is critical for diagnosing, monitoring and selecting therapies for various cancers. While advanced detection methods, such as polymerase chain reaction and next-generation sequencing, are highly accurate, they require thermal cycling, expensive equipment and specialised laboratory facilities. Supported by the Marie Skłodowska-Curie Actions programme, the PEAKRAS project aims to develop a highly sensitive, decentralised point-of-care testing platform for KRAS oncogene mutations. Based on a photoelectrochemical approach, the platform combines mismatch hairpin recycling and singlet oxygen redox cycling, creating a double layer of signal amplification to achieve an ultralow detection limit. This can be integrated into portable testing apparatus, making early cancer screening more affordable and accessible.

Objective

Cancer causes ~10 million deaths annually and a projected $25.2 trillion economic burden by 2050. Nearly half of cases are diagnosed late, underscoring the need for rapid and sensitive diagnostic tools. The KRAS oncogene is a major driver of colorectal, pancreatic, and lung cancers and serves as a critical biomarker for early detection, prognosis, treatment selection, and recurrence monitoring. With approved KRAS inhibitors and >85 investigational agents, the demand for accurate mutation testing is rising.

Current circulating tumor DNA assays rely on polymerase chain reaction (PCR) and next-generation sequencing (NGS), which achieve low mutant allele fraction (MAF) thresholds but require thermal cycling, costly instruments, and central laboratories. Optical and electrochemical alternatives simplify hardware but remain limited to picomolar detection and often lack selectivity in high wild-type backgrounds.

To address these challenges, I introduce PEAKRAS, a highly sensitive, dual-amplification photoelectrochemical (PEC) assay for KRAS mutation detection. The platform physically integrates mismatch hairpin recycling with singlet oxygen–mediated PEC redox cycling, enabling two layers of amplification without thermal cycling or electrode modification. This design targets a limit of detection of 0.1–10 fM while enabling reliable discrimination of mutant alleles below 1% MAF in plasma. By combining molecular selectivity encoded in mismatch hairpin kinetics with a simple, portable PEC transduction scheme, PEAKRAS overcomes major barriers to point-of-care mutation testing.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

(opens in new window) HORIZON-MSCA-2025-PF

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Coordinator

UNIVERSITEIT ANTWERPEN
Net EU contribution
€ 216 240,00
Address
PRINSSTRAAT 13
2000 Antwerpen
Belgium
Region
Vlaams Gewest Prov. Antwerpen Arr. Antwerpen
Activity type
Higher or Secondary Education Establishments
Links
Total cost
No data