Magnetofluid-Integrated Multicolor Immunochip for Visual Analysis of Neutralizing Antibodies to SARS-CoV-2 Variants.

The global spread of SARS-CoV-2 virus has severely affected human health, life, and work. Vaccine immunization is considered to be an effective means to protect the body from infection. Therefore, timely analysis of the antibody level is helpful to identify people with low immune response or attenuated antibodies so as to carry out targeted and precise vaccine booster immunization. Herein, we develop a magnetofluid-integrated multicolor immunochip, as a sample-to-answer system in a fully enclosed space, for visual analysis of neutralizing antibodies of SARS-CoV-2. Generally, this chip adopts an innovative three-dimensional two-phase system that utilizes mineral oil to block the connection between reagent wells in the vertical direction and provides a wide interface for rapid and nondestructive shuttle of magnetic beads during the immunoassay. In order to obtain visualized signal output, gold nanorods with a size-dependent color effect are used as the colorful chromogenic substrates for evaluation of the antibody level. Using this chip, the neutralizing antibodies were successfully detected in vaccine-immunized volunteers with 83.3% sensitivity and 100% specificity. Furthermore, changes in antibody levels of the same individual over time were also reflected by the multicolor assay. Overall, benefiting from simple operation, airtight safety, and nonrequirement of external equipment, this platform can provide a new point-of-care testing strategy for alleviating the shortage of medical resources and promoting epidemic control in underdeveloped areas.

DNA-Programmed Orientation-Ordered Multivalent Microfluidic Interface for Liquid Biopsy.

Aptamer-functionalized microfluidic interfaces hold great potential for liquid biopsies owing to their programmable nature. However, most previous studies have focused on development of multivalent aptamers to improve binding affinity, while ignoring aptamer orientation on microfluidic interfaces, resulting in suboptimal accessibility and affinity. Herein, we report a Cubic DNA Nanostructure (CDN)-programmed strategy to precisely control the orientation and valency of the Aptamer on a microfluidic interface (CDN-Apt-Chip) for enhancing the capture and release of circulating tumor cells (CTCs). We demonstrate that the ordered orientation and multivalent configuration can synergistically increase the binding affinity of aptamers toward CTCs. By using CDN-Apt-Chip, we successfully isolated CTCs from the peripheral blood of T-cell leukemia patients and discriminated T-cell leukemia patients from healthy volunteers. Furthermore, the captured CTCs were nondestructively released via nuclease treatment. We then performed T-cell receptor sequencing on the released cells to demonstrate the compatibility with downstream analysis. Overall, this study provides a new paradigm for interface regulation of functional microfluidic chips and advances the clinical translation of aptamer-based liquid biopsy.