In recent years, highly sensitive and selective as well as cost-effective sensing and detection of bio-molecules (e.g. virus,
bacterial, DNA and protein) by MEMS/NEMS (Micro-/Nano Electro-Mechanical-System) structures have attracted extensive attention for its importance in clinical diagnostics, treatment, and various genome projects. Meanwhile, substantial research efforts have been spent on the improvement of sensitivity of BioMEMS structures. Among a variety of methods that have been investigated, surface modification by nanoparticles (NPs) turns out to be an attractive way, which provides a platform for the enhancement of the sensitivity for biosensor devices. However, conventional applications for surface modification were mostly implemented on microelectrodes. This paper is going to present the self-assembly surface binding of nano-gold particle and functional MWCNT on the cantilever sensor, which can easily facilitate biomolecular detection by resonance frequency shift. Its sensitivity can be improved due to the large binding area of probes to the targeting biomolecules. The LPCVD SiN low-stress rectangular cantilever is produced by laser micromachining and alkaline KOH
etching, which is a maskless, simple, convenient, fast-prototyping way to produce such cantilever sensor for biomolecular detection. The commercially available Atomic Force Microscopy (AFM) cantilevers are also used to verify the concept.
Silicon-based microelectrode chips are useful tools for temporal recording of neurotransmitter releasing from
neural cells. Both invasive and non-invasive methods are targeted by different group researchers to perform
electrical stimulating on neural cells. A microfabricated microelectrodes integrated biochip will be presented in this
paper, which describes the dopaminergic cells growing on the chip directly. The dopamine exocytosis can be
detected non-invasively from drug incubated dopaminergic cells growing on the chip.
The abovementioned silicon-based electrochemical sensor chip has been designed with an electrode array located
on the bottom of reaction chamber and each electrode is individually electrical controlled. MN9D, a mouse
mesencephalic dopaminergic cell line, has been grown on the surface of the biochip chamber directly. Dopamine
exocytosis from the chip-grown MN9D cells was detected using amperometry technology. The amperometric
detection limit of dopamine of the biochip microelectrodes was found from 0.06μM to 0.21μM (S/N=3) statistically
for the electrode diameters from 10 μm to 90 μm, the level of dopamine exocytosis from MN9D cells was
undetectable whithout drug incubation. In contrast, after MN9D cells were incubated with L-dopa, a dopamine
precursor, K+ induced dopamine extocytosis was temporally detected.
The microelectrodes integrated biochip provides a non-invasive, temporal detection of dopamine exocytosis from
dopaminergic cells, and holds the potential for applications in studying the mechanisms of dopamine exocytosis,
and drug screening. It also provides a tool for pharmaceutical research and drug screening on dopaminergic cells,
extendably to be used for other cell culture and drug effects study.
Numerous studies have been done in studying the etching rates of the isotropic HF/HNO<sub>3</sub>/CH<sub>3</sub>COOH (or HNA) etchant for silicon in terms of the compositions of the solution. It is well known that the HNA etchant is an autocatalytic solution. Controlling its reaction rate is more complicated than just fixing the ratios of the reagent components - HF, HNO<sub>3</sub>, H<sub>3</sub>COOH. Sometimes, researchers may experience a runaway reaction, surprisingly even with the same composition used before. Researchers should also look into some chemical engineering aspects - such as etch-area or etchant-volume that can affect the dissipation of the heat generated and the self generated catalyst - HNO<sub>2</sub>. All these are very important in terms of the chemical safety inside a MEMS research laboratory. In this study, HNA solutions with similar compositions were used to demonstrate how the runaway reaction could start as a function of etch area, etchant volume, or etch-area:etchant-volume ratio. A larger area would make the reaction go faster, and might increase the chance of running into an uncontrollable manner easily. Usually, using less amount of HNA solution might be a good practice for waste minimization. However, by over doing it, the heat and the HNO<sub>2</sub> generated from the reaction could be accumulated too fast and they might be able to make the reaction out of control. HNA is an autocatalytic etchant and the HNO<sub>2</sub> generated is usually required to keep the reaction going. Thus it is desirable to keep the mass transfer low at the beginning of the etching, in order to keep the HNO<sub>2</sub>. Small amount of heat can also help to accelerate the reaction. However, the mass transfer and the heat transfer need to be controlled properly as reaction proceeds. In the case without mechanical setup for controlling the mass transfer and the heat transfer, the volume of the solution will become the major to carry out these tasks through natural convection and diffusion. In our study, we have demonstrated in simple ways on how to control and safe guard the etching reaction from runaway.
Boron nitride thin film has a very unique characteristic of extremely high chemical inertness. Thus, it is a better hard mask than silicon nitride for aggressive etching solutions, such as the isotropic HF/HNO<sub>3</sub>/CH<sub>3</sub>COOH (or HNA) etchant for silicon. However, because of its high chemical inertness, it is also difficult to remove it. Plasma etching with Freon gases can etch the boron nitride film, but it is unselective to silicon, silicon dioxide or silicon nitride. Cleaning up the boron nitride film with plasma etching will usually leave a damaged or foggy surface. A special wet chemical solution has been developed for etching or cleaning boron nitride film selectively. It can etch boron nitride, but not the coatings or substrates of silicon, silicon nitride and silicon dioxide. It is a very strong oxidizing agent consisting of concentrated sulfuric acid (H<sub>2</sub>SO<sub>4</sub>) and hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>), but different from the common Piranha Etch. It may be even more interesting to understand the logic or secret behind of how to formulate a new selective etching solution. Various chemical and chemical engineering aspects were considered carefully in our development process. These included creating the right electrochemical potential for the etchant, ensuring large differences in chemical kinetics to make the reactions selective, providing proper mass transfer for removing the by products, etc.