In vivo wireless ethanol vapor detection in the Wistar rat.

Traditional alcohol studies measure blood alcohol concentration to elucidate the biomedical factors that contribute to alcohol abuse and alcoholism. These measurements require large and expensive equipment, are labor intensive, and are disruptive to the subject. To alleviate these problems, we have developed an implantable, wireless biosensor that is capable of measuring alcohol levels for up to six weeks. Ethanol levels were measured in vivo in the interstitial fluid of a Wistar rat after administering 1 g/kg and 2 g/kg ethanol by intraperitoneal (IP) injection. The data were transmitted wirelessly using a biosensor selective for alcohol detection. A low-power piezoresistive microcantilever sensor array was used with a polymer coating suitable for measuring ethanol concentrations at 100% humidity over several hours. A hydrophobic, vapor permeable nanopore membrane was used to screen liquid and ions while allowing vapor to pass to the sensor from the subcutaneous interstitial fluid.

A spectroscopic investigation of the shape dependency of gold nanoparticles grown on roughened surfaces.

We present an investigation of the optical excitation of surface plasmons on Au films deposited on roughened surfaces by using a glancing angle deposition technique. By adjusting the deposition parameters of calcium fluoride and Au thin films, the spectral position of the surface plasmon resonances can be shifted through the green and into the near infrared region. In particular, we find that a rougher surface with obliquely deposited Au produces distinct spheroid-shaped nanoparticles (NPs). This results in stronger resonances with narrower linewidths, whereas smoother films result in broad red-shifted absorption. Imaging with an atomic force microscope and a scanning electron microscope provides information of NP geometry which are used as inputs for theoretical simulations of the observed spectra. The consequence of geometry distributions and inter-particle interactions are discussed. The ability to control the shape, therefore the optical response, of Au NPs over an arbitrarily large active area is of paramount importance in nano-science, especially in biological sensing applications and surface enhanced Raman scattering.

Nonradiative surface plasmon assisted microscale Marangoni forces.

When a liquid droplet experiences a temperature inhomogeneity along its bounding surface, a surface energy gradient is engendered, which when, in a continuous sense, exceeding a threshold, results in a convective flow dissipating the energy. If the associated temperature gradients are sustained by the interface between the liquid and a supporting substrate, the induced flow can result in the lateral motion of the droplet overcoming the viscosity and inertia. Recently, pico-liter adsorbed and applied droplets were shown experimentally to be transported, and divided by the decay of optically excited surface plasmons into phonons in a thin gold foil. The decaying events locally modify the temperature of the liquid-solid interface, establishing microscale thermal gradients of sufficient magnitude for the droplet to undergo thermocapillary flow. We present experimental evidence of such gradients resulting in local surface modification associated with the excitation of surface plasmons. We show theoretically that the observed effect is due to Marangoni forces, and computationally visualize the flow characteristics for the experimental parameters. As an application based on our results, we propose a method for an all-optical modulation of light by light mediated by the droplet oscillations. Furthermore, the results have important consequences for microfluidics, droplet actuation, and simultaneous surface plasmon resonance sensing and spectroscopy.

Microscale Marangoni actuation: all-optical and all-electrical methods.

We present experimental results from an all-optical microfluidic platform that may be complimented by a thin film all-electrical network. Using these configurations we have studied the microfluidic convective flow systems of silicone oil, glycerol, and 1,3,5-trinitrotoluene on open surfaces through the production of surface tension gradients derived from thermal gradients. We show that sufficient localized thermal variation can be created utilizing surface plasmons and/or engaging individually addressable resistive thermal elements. Both studies manipulate fluids via Marangoni forces, each having their unique exploitable advantages. Surface plasmon excitation in metal foils are the driving engine of many physical-, chemical-, and bio-sensing applications. Incorporating, for the first time, the plasmon concept in microfluidics, our results thus demonstrate great potential for simultaneous fluid actuation and sensing.

Marangoni forces created by surface plasmon decay.

We present optical microfluidic manipulation of silicone oil and glycerol via surface tension driven forces sustained by surface plasmon deexcitation energy. The phonon energy associated with the decaying optically excited surface plasmons in a thin gold foil creates thermal gradients capable of actuating fluid flows. Spectral dependence of the plasmon decay length and control of optical beam characteristics are shown to provide a means for further manipulation.

Modulation of multiple photon energies by use of surface plasmons.

A form of optical modulation at low pulse rates is reported in the case of surface plasmons excited by 1.55-microm photons in a thin gold foil. Several visible-photon energies are shown to be pulsed by the action of the infrared pulses, the effect being maximized when each visible beam also excites surface plasmons. The infrared surface plasmons are implicated as the primary cause of thermally induced changes in the foil. The thermal effects dissipate in sufficiently small times so that operation up to the kilohertz range in pulse repetition frequency is obtained. Unlike direct photothermal phenomena, no phase change is necessary for the effect to be observed.

Probing large area surface plasmon interference in thin metal films using photon scanning tunneling microscopy.

The interference of surface plasmons can provide important information regarding the surface features of the hosting thin metal film. We present an investigation of the interference of optically excited surface plasmons in the Kretschmann configuration in the visible spectrum. Large area surface plasmon interference regions are generated at several wavelengths and imaged with the photon scanning tunneling microscope. Furthermore, we discuss the non-retarded dispersion relations for the surface plasmons in the probe-metal system modeled as confocal hyperboloids of revolution in the spheroidal coordinate systems.

Manipulation of microcantilever oscillations.

Experimental observation of self-sustaining oscillations via a delayed feedback system is presented for a rectangular silicon microcantilever. The system is modeled as one and two-dimensional damped oscillator and the resulting delay differential equations are studied in frequency and time domain. The shortcomings of each model are outlined, and an improved formulation of the dynamics of the cantilever is presented.

Observation of Knudsen effect with microcantilevers.

The Knudsen effect is estimated theoretically and observed experimentally using a U-shaped silicon microcantilever. Though Knudsen forces are extremely small in most cases involving microcantilevers, there exist situations where these forces can be significant and may be important in atomic force microscopy and in microelectromechanical systems (MEMS). The criteria for the presence of Knudsen forces are outlined and an analytical expression in the form of a linear function of the pressure is given for the force in the free molecular regime. The experimental results display peaks in the transitional regime while varying linearly in the molecular regime.

Thermal transpiration at the microscale: a Crookes cantilever.

Local temperature inhomogeneities in systems containing micron and submicron objects can result in unexpected consequences. If the mean free path of the host gas constituents is comparable to a characteristic length of the system, then a net exchange of momentum occurs between the constituents and the involved surfaces. For a given temperature gradient and a given pressure range, this results in the presence of Knudsen and Knudsen-like forces (KF). The pressure dependence of these forces has been studied using a microelectromechanical system composed of a microcantilever near a substrate surface. Nano-Newton scale KF are observed by the bending of the microcantilever as monitored by the charge variation on the microcantilever-substrate assembly in a capacitive mode.

Telesensor integrated circuits.

Progress in personal computing has recently permitted small research programs to design and simulate application-specific integrated circuits (ASICs). Inexpensive fabrication of silicon chips can then be obtained using chip foundries, and quite complex circuits can be greatly reduced in size with an accompanying increase in certain performance characteristics. Within the past 5 years it has also become possible to design ASICs which can transmit and receive radio signals and which thus may be employed in applications in which wired connections for input and output of signals are not practicable. We are currently developing research-grade prototype ASICs for the monitoring of human vital signs. In this case one or more sensors placed on an ASIC provides a signal to be transmitted a distance of 2-3 meters to a receiver/display unit. The use of ASIC telesensors provides the possibility of wireless monitoring, including long-term monitoring, with inexpensive and unencumbering devices. Their self-contained nature permits a number of potential uses in future biomedical applications as new sensors are devised which are amenable to deployment on silicon.

Photon scanning-tunneling microscopy of unstained Mammalian cells and chromosomes.

The photon scanning-tunneling microscope (PSTM) yields optical topographical images of samples that are thin or that are transparent at the wavelength used. A range of sample sizes can be imaged extending to well below the diffraction limit for sufficiently flat samples. But samples of the order of several to many micrometers in size can be analyzed with less-refined resolution if total internal reflection can be made to occur in the sample. We used the PSTM to examine the optical topography of mouse and human cells and of chromosomes that are unstained. Our objectives were to demonstrate the images as an alternative to conventional microscopy and to provide a sample-preparation methodology that will later permit localized, simultaneous fluorescence or absorption spectroscopy with the signals collected by the probe tip. Furthermore, the PSTM's ability to produce optical profiles in air and in water was tested to establish the basis for future investigation of possible abnormalities in the chromosomes. That is, we considered both physical and biological objectives. To this end we utilized the 442-nm line of a He-Cd laser as well as the 633-nm line from a He-Ne laser, the resulting image quality being tested partly to ascertain the increased effects of scattering at the smaller wavelength. It is shown that adequate resolution and signal-to-noise ratio can be obtained with the shorter wavelength even in the presence of intensity fluctuations from the laser, thus showing that fluorescence and absorption studies can be expected to be practicable.

Environment effects on surface-plasmon spectra in gold-island films potential for sensing applications.

The effects of the local dielectric environment on the surface-plasmon resonances of annealed gold-island films as a potential for sensing applications are studied experimentally and modeled theoretically. Gold-island films were annealed at 600 degrees C to produce spheroidal shape particles that exhibit well-resolved resonances in polarized, angle-resolved, absorption spectra. These resonances are shifted in different amounts by the depolarization effect of the surrounding medium (liquids with various refraction indices). Cross-section calculations based on nonretarded, single-particle, dielectric interaction for these various configurations are presented and are found to be in good agreement with the experimental observations. The results show an interesting potential for biosensing or environmental monitoring applications.

Atomic force microscopy of DNA on mica and chemically modified mica.

Atomic force microscopy (AFM) was used to image circular DNA adsorbed on freshly cleaved mica and mica chemically modified with Mg(II), Co(II), La(III), and Zr(IV). Images obtained on unmodified mica show coiling of DNA due to forces involved during the drying process. The coiling or super twisting appeared to be right handed and the extent of super twisting could be controlled by the drying conditions. Images of DNA observed on chemically modified surfaces show isolated open circular DNA that is free from super twisting, presumably due to strong binding of DNA on chemically modified surfaces.

Electrostatic spraying of DNA molecules for investigation by scanning tunneling microscopy.

We have investigated electrostatic spraying of DNA onto gold surfaces as an alternative sample-preparation technique for STM studies. Preliminary results show that a higher distribution of isolated strands as well as well ordered aggregates can be obtained with this technique when compared with electrodeposition or drop evaporation. In many places, the well ordered aggregates were found to cleave in a direction perpendicular to their length after repeated scanning in the same direction.

Scanning tunneling microscopy of DNA: a novel technique using radiolabeled DNA to evaluate chemically mediated attachment of DNA to surfaces.

pBS+ plasmid deoxyribonucleic acid (DNA) was imaged by scanning tunneling microscopy (STM) after mounting microdroplets by aerosol deposition onto heated epitaxial gold surfaces. However, the instability of the adsorbate to forces exerted by the tunneling tip points out the need for more aggressive bonding of molecules to surfaces. We describe a sensitive assay for the qualitative and quantitative evaluation of chemical agents to influence binding of DNA to surfaces using 32P-labeled pBS+ plasmid DNA. We propose that such an assay can make an important contribution to immobilization techniques prior to STM imaging.

Imaging isolated strands of DNA molecules by atomic force microscopy.

We have employed an atomic force microscope (AFM) to image in air isolated strands of pBS+ plasmid DNA adsorbed onto freshly cleaved mica. At a DNA concentration below 0.3 micrograms/ml isolated strands of the plasmid DNA are usually seen, while for concentrations higher than 3 micrograms/ml a uniform coverage of interconnected DNA strands was observed. We found that the contrast and the width of DNA were dependent upon humidity. When the relative humidity exceeds 60%, negative contrast images with strand widths 20 times the width of DNA are found, while positive contrast images with 7 to 10 times the width of DNA are found when the humidity is below 30%. By placing the AFM in an environment where the humidity could be controlled, we were able to switch between positive and negative contrasts.

Scanning tunneling microscopy and spectroscopy of plasmid DNA.

We present scanning tunneling microscope (STM) images of uncoated deoxyribonucleic acid (DNA) electrochemically mounted on highly-oriented pyrolytic graphite (HOPG) and imaged in air. Images of linear abnormalities inherent to HOPG surfaces that can be confused with DNA are also presented. Scanning tunneling spectroscopic (STS) images generated by superimposing a small, high frequency ac bias onto the dc tunnel bias and recording the ac current signal were taken simultaneously with the topographic images. These spectroscopic images reveal contrast due to local conductivity variations and can be used to differentiate DNA molecules from graphite artifacts.

A spontaneous outbreak of polychlorinated biphenyl (PCB) toxicity in rhesus monkeys (Macaca mulatta): clinical observations.

A spontaneous, progressive disease occurred in a large domestic breeding colony of rhesus monkeys (Macaca mulatta). The disease was characterized by slow but continuous weight loss, alopecia, acne, facial edema, diarrhea and trauma from other monkeys. Breeding efficiency was impaired with a high incidence of abortions and stillbirths. Live offspring were small and unthrifty contributing to a high infant mortality rate. The cause of this disease was polychlorinated biphenyls (PCSs) which were present in the concrete sealant on the cage floors. Removing the sealant and resurfacing the floors alleviated the problem.

Suspected ascorbic acid deficiency in a colony of squirrel monkeys (Saimiri sciureus).

Subperiosteal cranial hematomas were observed in five female squirrel monkeys. The absence of trauma in the clinical history, the characteristic clinical changes, and the pathological lesions suggested that the animals were scorbutic. Analysis of feed which was soaked in water, or left on the ground for varying time periods at different temperatures, indicated that there was loss of ascorbic acid. During the manufacture of monkey feed, ascorbic acid is dusted on as a final process. The practice of soaking feed resulted in the "washing off" or the destruction of ascorbic acid. This disease outbreak emphasized the important of management practices in a primate colony.