Simple and Low‐Cost Sampling of Cell‐Free Nucleic Acids from Blood Plasma for Rapid and Sensitive Detection of Circulating Tumor DNA

Abstract

Cell‐free nucleic acids (cfNAs) are emerging diagnostic biomarkers for monitoring the treatment and recurrence of cancers. In particular, the biological role and clinical usefulness of cfNAs obtained from the plasma of patients with various cancers are popular and still intensely explored, yet most studies are limited by technical problems during cfNA isolation. A dimethyl dithiobispropionimidate (DTBP)‐based microchannel platform that enables spontaneous cfNA capture in 15 min with minimal cellular background and no requirements for use of bulky instruments is reported first. This platform identified KRAS and BRAF hot‐spot mutations following cfDNA isolation from the blood plasma and tissues obtained from 30 colorectal cancer patients. The correlation of mutations between the primary tissues and plasma from the patients was high using this platform with whole genome sequencing compared to the spin‐column method. This platform can also be combined with various detection approaches (biooptical sensor, Sanger sequencing, and polymerase chain reaction (PCR)) for rapid, simple, low‐cost, and sensitive circulating tumor DNA detection in blood plasma. The efficiency and versatility of this platform in isolating cfNAs from liquid biopsies has applications in cancer treatment and precision medicine.

The interplay of circulating tumor DNA and chromatin modification, therapeutic resistance, and metastasis

“…However, ctDNA has not been standardized as a biomarker, which means that the results of the ctDNA analysis may not be comparable due to technological differences [69]. To fully incorporate liquid biopsies into clinical practice, there is a glaring need to standardize methods, such as the way blood samples are collected and stored, the technical specifications of the assays, and ctDNA isolation [58,63,70,71].…”

“…With the development of detection technology, a new ctDNA sampling technology is urgently needed to overcome the disadvantages of existing methods, such as high cost, slow speed, low sensitivity, and complexity. (The dimethyl dithiobispropionimidate (DTBP)-based microchannel platform [71] is a good attempt.) Additionally, during the experiment, the sensitivity of the detection method should be reasonably regulated to minimize the probability of a false positive or false negative result [63,73].…”

ctDNA Detection in Microfluidic Platform: A Promising Biomarker for Personalized Cancer Chemotherapy

“…(b) Micropillar-based plastic microfluidic surface to detect cfDNA; more than 90% of purities of cfDNA was extracted [69]. (c) Microcolumnand microwell-based microfluidic for cfDNA isolation [71]. 6 Journal of Sensors activated plastic microfluidic surface.…”

“…The chip also proved can be utilized for clinical disease detection by extracted cfDNA from plasma samples of colorectal and non-small-cell lung cancer patients to detect KRAS mutation gene. Another new method was introduced by Aravanis et al by sampling cfDNA from blood plasma of colorectal cancer patients for ctDNA detection [71]. The microwells and microcolumn-based microfluidic platform used dimethyl dithiobispropionimidate (DTBP) for ctDNA isolation and integrated with Sanger sequencing method for ctDNA validation.…”

Liquid biopsy for rectal cancer: A systematic review

“…In the European Union, the incidence of RC is ~125000 per year, i.e. ~35% of the total colorectal cancer incidence, reflecting [15][16][17][18][19][20][21][22][23][24][25] cases/100 000 population per year and is predicted to further increase in both genders.…”