Microfluidic approaches to next- generation sequencing library preparation: innovations, clinical integration and point-of-care settings.

Abstract

Introduction: Next-generation sequencing (NGS) has revolutionized genomics by enabling high-throughput, cost-effective analysis of nucleic acids for both research and clinical use. Despite advances in sequencing technology, library preparation remains a major bottleneck owing to high reagent consumption, labor-intensive workflows, long hands-on-time, and susceptibility to human error.

Areas covered: This review examines recent advances in microfluidic NGS library preparation across four platform types-: continuous-flow systems, droplet microfluidics, digital microfluidics (DMF), and integrated lab-on-chip devices. These technologies reduce reagent consumption by 10 to 200 times, enables high-quality libraries from picogram-scale DNA or even single cells, and automate complex workflows within enclosed systems. Their applications in liquid biopsy, pathogen detection, prenatal testing, and epigenomic profiling demonstrate considerable clinical promise. However, fabrication complexity, lack of standardization, biofouling, and high instrument costs hinder widespread adoption, particularly in resource-limited settings. Advancements in AI, thermal control, long-read sequencing, and portable microfluidics are helping to overcome these issues.

Expert opinion: Microfluidic library preparation can streamline NGS workflows by improving automation, reproducibility, and accessibility, broadening sequencing use in research, clinical diagnostics, and point-of-care settings.