Complex Nucleic Acid Hybridization Reactions inside Capillary-Driven Microfluidic Chips

Small. 2020 Dec;16(49):e2005476. doi: 10.1002/smll.202005476. Epub 2020 Nov 17.

Abstract

Nucleic acid hybridization reactions play an important role in many (bio)chemical fields, for example, for the development of portable point-of-care diagnostics, and often such applications require nucleic acid-based reaction systems that ideally run without enzymes under isothermal conditions. The use of novel capillary-driven microfluidic chips to perform two isothermal nucleic acid hybridization reactions, the simple opening of molecular beacon structures and the complex reaction cascade of a clamped-hybridization chain reaction (C-HCR), is reported here. For this purpose, reagents are arranged in a self-coalescence module (SCM) of a passive silicon microfluidic chip using inkjet spotting. The SCM occupies a footprint of ≈7 mm2 of a ≈0.4 × 2 cm2 microfluidic chip. By means of fluorophore-labeled DNA probes, the hybridization reactions can be analyzed in just ≈2 min and using only ≈3 µL of the sample. Furthermore, the SCM chip offers a variety of reagent delivery options, allowing, for example, the influence of the initiator concentration on the kinetics of C-HCR to be investigated systematically with minimal sample and time requirements. These results suggest that self-powered microfluidic chips equipped with a SCM provide a powerful platform for performing and investigating complex reaction systems.

Keywords: capillary-driven chip; clamped-hybridization chain reaction; molecular beacon reaction; self-coalescence module; signal amplification.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Fluorescent Dyes
  • Microfluidic Analytical Techniques*
  • Microfluidics
  • Nucleic Acid Amplification Techniques
  • Nucleic Acid Hybridization
  • Nucleic Acids*

Substances

  • Fluorescent Dyes
  • Nucleic Acids