Abstract

Monitoring biological reactions using the mechanical response of macromolecules is an alternative approach to immunoassays for providing real-time information about the underlying molecular mechanisms. Although force spectroscopy techniques, e.g. AFM and optical tweezers, perform precise molecular measurements at the single molecule level, sophisticated operation prevent their intensive use for systematic biosensing. Exploiting the biomechanical assay concept, we used micro-electro mechanical systems (MEMS) to develop a rapid platform for monitoring bio/chemical interactions of bio macromolecules, e.g. DNA, using their mechanical properties. The MEMS device provided real-time monitoring of reaction dynamics without any surface or molecular modifications. A microfluidic device with a side opening was fabricated for the optimal performance of the MEMS device to operate at the air-liquid interface for performing bioassays in liquid while actuating/sensing in air. The minimal immersion of the MEMS device in the channel provided long-term measurement stability (>10 h). Importantly, the method allowed monitoring effects of multiple solutions on the same macromolecule bundle (demonstrated with DNA bundles) without compromising the reproducibility. We monitored two different types of effects on the mechanical responses of DNA bundles (stiffness and viscous losses) exposed to pH changes (2.1 to 4.8) and different Ag+ concentrations (1 μM to 0.1 M).

Highlights

  • To cite this version: Mehmet Tarhan, Nicolas Lafitte, Yannick Tauran, Laurent Jalabert, Momoko Kumemura, et al

  • Force spectroscopy techniques, e.g. AFM and optical tweezers, perform precise molecular measurements at the single molecule level, sophisticated operation prevent their intensive use for systematic biosensing

  • Unlike some of the other well-established methods that are often limited to smaller sized molecules, e.g. nuclear magnetic resonance (NMR)[2] and surface plasmon resonance (SPR)[3], force spectroscopy techniques, e.g. optical tweezers[4,5], magnetic tweezers[6,7,8] and AFM9,10, provide sensitive measurements on mechanical properties spanning six orders of magnitude in length (10−10–10−4 m) including macromolecules[1,11,12]

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Summary

Introduction

To cite this version: Mehmet Tarhan, Nicolas Lafitte, Yannick Tauran, Laurent Jalabert, Momoko Kumemura, et al. Unlike some of the other well-established methods that are often limited to smaller sized molecules, e.g. nuclear magnetic resonance (NMR)[2] and surface plasmon resonance (SPR)[3], force spectroscopy techniques, e.g. optical tweezers[4,5], magnetic tweezers[6,7,8] and AFM9,10, provide sensitive measurements on mechanical properties spanning six orders of magnitude in length (10−10–10−4 m) including macromolecules[1,11,12]. These techniques provide information at the single molecule level to reveal novel properties of various different molecules. A rapid, practical, time- and cost-efficient, automated and preferably portable method is beneficial as a complementary or alternative method to the conventional techniques to be employed even by non-specialists

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