Bis(sulfosuccinimidyl)suberate-Based Helix-Shaped Microchannels as Enhancers of Biomolecule Isolation from Liquid Biopsies

Most studies of ultrasensitive diagnosis of biomolecules from liquid specimens are limited by problems during sample preparation steps, including enrichment and isolation of biomolecules. Here we report a novel platform combining bis(sulfosuccinimidyl)suberate (BS3) and helix-shaped microchannels (BSH) to change the sample preparation paradigm. This BSH system is composed of BS3 for pathogen enrichment and nucleic acid isolation by electrostatic and covalent interaction, and helix-shaped microchannels to minimize sample loss and remove bubbles in large liquid specimens without pH change. The system detected Mycobacterium tuberculosis following enrichment and isolation of 10 mL of liquefied sputum from 11 patients with tuberculosis. Moreover, the system identified KRAS mutations following cell-free DNA isolation of blood plasma from 10 patients with colorectal cancer. This system allows ultrasensitive diagnosis in various disease applications with large volumes of liquid samples.