Blood is rich in important markers such as protein and nucleic acid, and the collection of blood samples is non-invasive, so disease diagnosis based on blood tests has become the most accessible strategy in clinical application. Compared with nucleic acids, protein markers are more stable and do not require extraction and amplification.
However, the abundance of proteins in the blood is wide, most of the reported protein biomarkers are susceptible to complex biological environments, and the concentrations in serum are usually very low. Thus, the detection of serum protein biomarkers is extremely challenging.
Recently, a research team led by Prof. TAN Weihong, Prof. LIU Yuan from the Hangzhou Institute of Medicine of the Chinese Academy of Sciences (CAS) proposed a high-throughput proteofish platform.
This study was published in Journal of the American Chemical Society.
Firstly, the scientists obtained a protein corona (MNP-PC) by incubating magnetic nanoparticles with serum samples. Then, they incubated the magnetic nanoparticles with a multi-aptamer cohort to obtain aptamer labeled MNP-PC (MNP-PCA) to simplify the complex protein information in the MNP-PC and transform it into aptamer information. They introduced eluted aptamers into the corresponding CRISPR signal detection system.
Through the complementary pairing of the aptamer and its specific crRNA sequence, the trans-cleavage activity of Cas12a on the substrate probe (FQ-DNA) was activated to generate fluorescence signals. Thus, the multiplex orthogonal detection platform (COMPASS) was constructed.
The researchers used the clinical non-small cell lung cancer (NSCLC) samples as a proof of concept, which demonstrated that the platform can diagnose NSCLC. Furthermore, they determined the four out of nine (FOON) panel to be the most cost-effective and accurate panel for COMPASS in NSCLC diagnosis. The diagnostic accuracy of NSCLC by the FOON panel with internal and external cohorts was 95.56% (ROC-AUC = 99.40%) and 89.58% (ROC-AUC = 95.41%), respectively.
Their developed COMPASS technology not only circumvents the challenging of low abundance proteins detection and avoids aptamer degradation in serum. Therefore, this novel COMPASS could lead to the development of a facile, cost-effective, intelligent, and high-throughput diagnostic platform for large-cohort cancer screening.
Original link: https://pubs.acs.org/doi/10.1021/jacs.4c03061
