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Biology subjects

Le, L. T. P.

Publications and source records attributed to Le, L. T. P..

2 recordsLinked to original sources

Rapid and reusable high-throughput microfluidics through modular assembly

High-throughput microfluidics has transformed biomedical research by enabling precise and parallel sample handling, but most devices are single-use due to channel occlusion and contamination from experiments. Alongside low fabrication yield and reduced experimental success associated with dense microfeatures, this creates a major bottleneck for scalable high-throughput applications. We present a rapid, reusable, and modular high-throughput microfluidic platform with integrated microvalves for automation. The platform employs a multilayer architecture consisting of a custom casing, PDMS layers with dense microfeatures for fluid handling and culture, and a glass substrate. Permanent bonding is applied only between control and fluid layers, while reversible bonding is used at all other interfaces, including the substrate. Because substrate is the primary cell-contact surface and can be readily detached, the remaining layers can be disassembled, thoroughly cleaned, and reused with minimal processing on a new substrate. This approach improves repeatability and experimental success while reducing preparation time from days to [~]2 hours. The disassemblable design also supports incorporation of application-specific layers between fluid layer and substrate, enhancing platform versatility for 3D culture. We validated performance through pressure/flow characterization and on-chip cell/organoid culture. Overall, our platform accelerates rapid high-throughput data generation across diverse biological applications.

bioengineering↗

Engineering Versatile Two-Dimensional Nanobody-Origami Architectures for Enhanced Antiviral Activity

Considering the serious global health burden posed by pathogenic viruses, the development of effective antiviral molecules and therapeutic strategies is critical for improving human health. Designing and synthesizing a versatile and biocompatible molecular platform offering neutralization of both coronaviruses and retroviruses, two virus families that are greatly problematic to the human population, remains a significant challenge. Here, we report a programmable and versatile platform built on a two-dimensional (2D) DNA origami that enables nanoscale spatial control of multivalent nanobody (Nb) patterns for a broad-spectrum antiviral application. By site-selectively conjugating a Nb to a DNA oligonucleotide and placing multiple of them to predefined sites on 2D DNA origami, we synthesized hybrid nano-architectures with tunable Nb patterns designed to approximately match the geometric presentation of viral surface proteins. We demonstrate that such specific Nb spatial configurations significantly enhance both viral binding affinity and neutralization potency. For SARS-CoV-2, a coronavirus, a triangular Nb pattern with matched spacing with the spike proteins achieved an IC50 of 1.52 nM, representing a 171-fold improvement over monomeric Nbs. Extending this strategy to a retroviral virus, Human Immunodeficiency Virus (HIV) by utilizing a gp120 spike-binding Nb, we observed a 233-fold increase in neutralization efficiency using a patterned 2D Nb nano-architecture. These findings suggest a generalizable and versatile platform strategy for engineering potent antiviral agents through spatially optimized Nb presentation for a corresponding viral pathogen, offering a promising avenue for future antibody and Nb-based drug development.

bioengineering↗