Abstract

Background
Electromagnetic frequencies up to a few terahertz (THz) can yield real-time and noninvasive measurements on biological matter. Unfortunately, strong absorption in aqueous solutions and low spatial resolution return difficult free-space investigations. A new approach based on integrated THz circuits was used. The authors designed and fabricated a BioMEMS (Biological MicroElectro-Mechanical System) compatible with microfluidic circulation and electromagnetic propagation. It is dedicated to the ex vivo detection of nitric oxide synthase (NOS) activity, which is involved in neurodegenerative phenomena.
Material and Method
The biological model was a leech's central nervous system. After its injury, the production of NO was observed and measured in the far-THz spectral domain. The nerve cord was put inside a BioMEMS realized in polydimethylsiloxane (PDMS) sealed on a glass wafer. Glass is a good material for supporting high-frequency integrated waveguides such as coplanar waveguides (CPWs). Measurements were performed with vectorial network analyser (VNA).
Results
The transmission parameter in the frequency range of 0.14-0.22 THz was measured through CPWs located just below the microchannel containing the injured leech nerve cord. The lesion caused a decreased transmission coefficient due to the NOS activity. L-NAME was injected inside the microchannel and it was verified that it inhibits this activity.
Conclusions
It was demonstrated that THz spectroscopy can detect a biochemical event, such as NOS activity around an injured leech's nerve cord, in real time. Future studies will be dedicated to quantitative measurements of the reaction products using the sophisticated management of several drugs allowed with microfluidic microsystems.

Keywords: Nitric Oxide - metabolism, NG-Nitroarginine Methyl Ester - pharmacology, Microfluidics - methods, Magnetics, Micro-Electrical-Mechanical Systems - methods, Hirudo medicinalis - physiology, Nitric Oxide Synthase - metabolism, Enzyme Inhibitors - pharmacology, Central Nervous System - physiology, Terahertz Spectroscopy - methods