Publication details

Clamp the LAMP: a photoelectrochemical platform for KRAS mutation detection via wild-type blocking

Authors

STRMISKOVÁ Johana VALVERDE Alejandro MORÁŇOVÁ Ludmila ARNOUTS Jorine ZAVADIL KOKÁŠ Filip KOLJENOVIC Senada ZWAENEPOEL Karen VANDAMME Timon BARTOŠÍK Martin DE WAEL Karolien

Year of publication 2026
Type Article in Periodical
Magazine / Source BIOSENSORS & BIOELECTRONICS
MU Faculty or unit

Faculty of Science

Citation
web https://www.sciencedirect.com/science/article/pii/S0956566326002496?dgcid=coauthor#kwrds0010
Doi https://doi.org/10.1016/j.bios.2026.118617
Keywords KRAS mutation detection; Clamp-inhibited LAMP; Locked nucleic acids; Wild-type suppression; Singlet oxygen; Photoelectrochemical biosensing
Attached files
Description KRAS mutations are among the most prevalent oncogenic alterations in colorectal, lung and pancreatic cancer, yet their detection remains analytically challenging in the presence of an overwhelming wild-type (WT) background. Here, we report a photoelectrochemical (PEC) genotyping platform that integrates clamp-inhibited loop-mediated isothermal amplification (C-LAMP) with enzyme-free singlet oxygen (1O2)-driven PEC transduction for mutation-selective KRAS detection. Locked nucleic acid (LNA) clamp probes selectively suppress WT amplification during isothermal amplification, enriching mutant alleles and enabling single-nucleotide variant (SNV) discrimination with high selectivity. Amplified products are magnetically captured and transduced into photocurrent via visible-light-induced 1O2 redox cycling, eliminating enzymatic reporters and reducing background interference. The C-LAMP/PEC platform achieves a limit of detection of 35 copies µL-1 (58 aM) and a minimum detectable variant allele frequency (VAF) of 4.8% in heterogeneous mutant/WT genomic DNA mixtures. Analytical performance was validated in cancer cell lines and in patient-derived fresh frozen tissues, showing complete concordance with Nanopore sequencing and droplet digital PCR (ddPCR) within the evaluated cohort (n = 16). This work introduces a robust and modular PEC biosensing strategy that combines molecular WT suppression with enzyme-free photoelectrochemistry, offering an economically competitive and instrumentation-simplified approach for clinically relevant KRAS mutation analysis toward decentralized testing.

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