Mong S. Marma

A film bulk acoustic resonator in liquid environments

A highly sensitive film bulk acoustic resonator (FBAR) mass sensor in liquid environments is described in this paper. A transmission line model is used to theoretically predict the dependence of the FBARs resonant frequency on added mass. FBAR performance in a liquid environment is experimentally characterized for the first time and the effects of the liquid nature and conductivity on the FBAR series and parallel resonant frequencies are investigated. A TiO2-coated FBAR is developed for sensitive mass sensing of metal ions in a liquid environment.

Synthesis, Chiral High Performance Liquid Chromatographic Resolution and Enantiospecific Activity of a Potent New Geranylgeranyl Transferase Inhibitor, 2-Hydroxy-3-imidazo[1,2-a]pyridin-3-yl-2-phosphonopropionic Acid

3-(3-Pyridyl)-2-hydroxy-2-phosphonopropanoic acid (3-PEHPC, 1) is a phosphonocarboxylate (PC) analogue of 2-(3-pyridyl)-1-hydroxyethylidenebis(phosphonic acid) (risedronic acid, 2), an osteoporosis drug that decreases bone resorption by inhibiting farnesyl pyrophosphate synthase (FPPS) in osteoclasts, preventing protein prenylation. 1 has lower bone affinity than 2 and weakly inhibits Rab geranylgeranyl transferase (RGGT), selectively preventing prenylation of Rab GTPases. We report here the synthesis and biological studies of 2-hydroxy-3-imidazo[1,2-a]pyridin-3-yl-2-phosphonopropionic acid (3-IPEHPC, 3), the PC analogue of minodronic acid 4. Like 1, 3 selectively inhibited Rab11 vs. Rap 1A prenylation in J774 cells, and decreased cell viability, but was 33-60x more active in these assays. After resolving 3 by chiral HPLC (>98% ee), we found that (+)-3-E1 was much more potent than (-)-3-E2 in an isolated RGGT inhibition assay, approximately 17x more potent (LED 3 microM) than (-)-3-E2 in inhibiting Rab prenylation in J774 cells and >26x more active in the cell viability assay. The enantiomers of 1 exhibited a 4-fold or smaller potency difference in the RGGT and prenylation inhibition assays.

Label-free detection of protein-ligand interactions in real time using micromachined bulk acoustic resonators

In this paper, we present a micromachined film bulk acoustic resonator (FBAR) to detect protein-ligand interactions in real-time. The surface of the FBAR device has a thin layer of gold deposited on it to immobilize thiol-modified biotin. The resonant frequency of the biotin modified FBAR was measured to decrease by 170 ppm when exposed to streptavidin solution with a concentration of 5×10−7 M, corresponding to an added mass of 120 pg on the FBAR surface due to the biotin-streptavidin interaction. Consequently, the biotin modified FBAR can be used to observe in real time the biotin-streptavidin interaction without the use of labeling or molecular tags. The FBAR can be used in a variety of protein-ligand systems, and be designed for testing in array formats to give high throughput screening for drug discovery.

Sequence Specific Label-Free DNA Sensing Using Film-Bulk-Acoustic-Resonators

A label-free biosensor (for detection of DNA sequences) based on film-bulk-acoustic-resonator (FBAR) is presented in this letter. The FBARs resonant frequency shifts to a lower value when a complementary single-strand DNA sequence is hybridized with a DNA probe sequence on an Au-coated FBAR surface. The sensor is capable of distinguishing a complementary DNA that is mismatched to a probe DNA by a single nucleotide. The label-free, highly sensitive and selective, and real-time detection of DNA sequence could easily be made into an array for combinatory DNA sequencing, and could possibly help geneticists to detect specific DNA sequences accurately and fast, without any expensive optical scanning or imaging.

Implantable resonant mass sensor for liquid biochemical sensing

This paper describes an implantable, resonant mass sensor (built on a micromachined probe with a piezoelectric thin film) for liquid mass sensing. The sensor is basically a film-bulk-acoustic resonator (FBAR) with a piezoelectric ZnO film and two Al layers sitting on a silicon nitride (SiN) diaphragm, which forms the tip portion of an implantable silicon probe for recording neuronal activities in a living biological tissue.

Mercuric Ion Sensing by a Film Bulk Acoustic Resonator

This paper describes a film bulk acoustic resonator (FBAR) mass sensor for detecting Hg²⁺ ion in water with excellent sensitivity and selectivity. When a thin Au film was deposited on the surface of an FBAR, the resonant frequency shifted to a lower value when the film was exposed to Hg²⁺ in aqueous solution. The FBAR sensor detected as low as 10^-9 M Hg²⁺ (0.2 ppb Hg²⁺) in water. Other ions such as K⁺, Ca²⁺, Mg²⁺, Zn²⁺, and Ni²⁺ had little or no effect on the resonant frequency of the FBAR. Coating of the FBAR Au surface with a self-assembled monolayer (SAM) of 4-mercaptobenzoic acid decreased the Hg²⁺ response.

Mercury ion sensing by film-bulk-acoustic-resonator mass sensor

This paper describes an FBAR (film bulk acoustic resonator) mass sensor for detecting Hg in liquid. With a thin Au film deposited on the surface of an FBAR, the FBARs resonant frequency shifts as Hg amalgamates on the Au surface. The FBAR sensor is measured to be capable of detecting a concentration of 10^-19 M Hg² (i.e., 0.2 ppb Hg²¹). Other cations such as K¹, Ca², Mg², Zn²¹, Ni² have shown to have little or no effect on the resonant frequency of the FBAR. Responses of the FBAR sensors coated with various thicknesses of Au film to a same concentration of Hg² have been compared. Finally, an FBAR with a thiol-compound-modified Au film is shown to have a smaller frequency shift than that with a pure Au film