The device presented is based on a supported membrane incorporating modified ion channels. Various analytes induced down regulation of the ion flux by interaction with specific binding sites or artificial ligands attached near the channel entrance. To set up such a device new types of stabilizing membrane supports had to be developed. The new support presented was deposited by electyropolymerization of 1,2-diaminobenzene onto metal electrodes thus exhibiting a highly charged surface. Negatively charged lipids formed SA- membranes tightly bound to that gel surface. Mixtures of biological lipids and archaeabacteria type bolaamphiphilic lipids minimized lipids minimized floating of the membrane layer. Various ligands were bound to the modified Bisgramicidin-A to interact with their specific antibodies. It turned out that it is vital to accurately coupled the ligand at a single functional hydroxy-group. Sensors were optimized using a metal/ligand and 2,4- dinitrophenol/polyclonal antibody setup. Summing up, highly stable supported membranes were formed, ion channel were functionally integrated into these membranes and molecule interactions of analytes with embedded ion channels were monitored.

Surface enhanced absorption of metal nano-clusters enabled us to transduce bioaffinity interactions highly amplifying the optical effect of changes in sensor surface coverage. The sensors were built depositing multiple nanoscale layers: at first silver or gold were sputtered onto oxygen plasma activated polycarbonate substrates to obtain a semitransparent metal cluster layer. Alternatively the primary metal layer was built of gold colloids covalently coupled to the activated polycarbonate. Next a chemically inert distance layer was applied e.g. by polymer-spinning. Finally a second cluster layer of e.g. gold colloids was coupled via bioaffinity interactions to the surface of the inert distance layer. The optical properties of the senor were found to be dependent on the size, shape and number of the metal-clusters as well as the distance between both metal cluster layers. For biomedical sensing the number and the spatial arrangement of biorecognitive bound metal clusters was transduced into an optical signal with high sensitivity. Since the defined spatial approach of colloids to the sensor surface alone creates the signal we could visually follow molecular binding events in real time. The first setups constructed were based on lectin-hexose or antibody-antigen interaction. The analytes were quantified via a distinct change of the spectral reflectivity of the sensor chip visible to the eye or measured by a miniaturized photometric device.

Planar waveguide interferometers provide an attractive sensing platform for biosensor applications. Advantages include small size, real-time sensing, multiple analyte detection on a chip, performance independent of wavelength and optical power, and nulling of thermal and mechanical noise. Limitations include slow diffusion time of the analyte to the functionalized surface, interference from non-specific binding and bulk index of refraction changes and a lack of reversibility. Combining certain techniques used in affinity chromatography and enzyme-linked immunosorbent assays and with an amplifying chemoselective film on the waveguide produces a sensor that is versatile, reusable and overcomes most of the above limitations. Work will be presented using an optical pH and ammonia sensor for detection.

We describe a biochip based on an integrated circuit photodiode array for use in medical diagnostics. The biochip is a self-contained device which has photosensors, amplifiers, discriminators and logic circuitry on board. The development and evaluation of various microchip system components of the genosensor are discussed. The performance of the DNA biochip device is illustrated with fluorescence detection of DNA probes specific to gene fragments of the human immuno-deficiency virus 1 system. The usefulness and potential to the DNA biochip technology for rapid and cost- effective medical diagnostics is discussed.

In this preliminary investigation, a two wavelength optical polarimetric system was used to show the potential of the approach to be used as an in vivo noninvasive glucose monitor. The dual wavelength method is shown as a means of overcoming two of them ore important problems with this approach for glucose monitoring, namely, motion artifact and the presence of other optically chiral components. The use of polarized light is based on the fact that the polarization vector of the light rotates when it interacts with an optically active material such as glucose. The amount of rotation of the light polarization is directly proportional to the optically active molecular concentration and to the sample path length. The end application of this system would be to estimate blood glucose concentrations indirectly by measuring the amount of rotation of the light beam's polarization state due to glucose variations within the aqueous humor of the anterior chamber of the eye. The system was evaluated in vitro in the presence of motion artifact and in combination with albumin, another interfering optical rotatory chemical component. It was shown that the dual wavelength approach has potential for overcoming these problems.

The noninvasive monitoring of sugars, and in particular, glucose using near-IR (NIR) spectroscopy would be useful for a number of applications including regulating the nutrients in cell culture medium, monitoring on-line processes in the food industry, and in vivo monitoring for control of glucose in DIabetic patients. The focus of this research was the investigation of the temperature effects across a 10.6 to 40.4 degrees C range on Fourier filtered and unfiltered single-beam as well as absorbance glucose and water NIR spectra. It is known that the positions of water absorption bands centered at 1.923 and 2.623 micrometers depend heavily on temperature effects while the glucose bands are temperature insensitive across this range. The water absorption bands were shown to shift to lower wavelengths while the distance between these bands increased with increasing temperatures. Partial least squares (PLS) calibration models were constructed at five separate temperatures, 15.7, 20.5, 25.5, 35.6, and 40.4 degrees C. When absorbance spectra were used with reference scans taken at the same temperature and PLS models were used, no significant difference in the standard error of prediction (SEP) was noted with temperature. Using PLS calibration with single-beam spectra at one temperature showed large SEPs at the other temperatures. The use of Fourier filtered single-beam spectra reduced the SEP but still showed an increase as large temperature differences were produced and the filtered single beam approach did not reduce the SEP to the level achieved with the absorbance spectra.

Nitric oxide (NO), in concentrations between 0 and 20 ppm, is currently being used as an inhaled agent to treat patients with post surgical complications and respiratory disorders. Because excessive levels of NO can be detrimental to the patient, NO must be monitored accurately and continuously. Currently available instruments have problems that limit their usefulness for this application. This paper discusses the development of an inexpensive, direct and continuous sensor for the measurement of inhaled nitric oxide. The sensor incorporates a 0.05 inch, gas permeable, flow-through liquid cell into a probe, which can be incorporated into a ventilator circuit. Sensor operation is based on the complexation reaction of NO with cytochrome-c, a biologically derived heme. The complex is monitored spectrophotometrically by measuring the absorbance in the visible region of the spectrum at 563 nm. The sensor is specific to NO in the presence of oxygen. This paper will address experiments to optimize sensitivity of the sensor. Increasing the flow rate and pressure of NO into the sensing chamber increased the optical absorbance at a high concentration of NO. Increasing the concentration of cytochrome-c increased the sensitivity of the sensor. The sensor is currently sensitive to a minimum concentration of 5 ppm and linear in the range of 5 to 175 ppm.

A cost-efficient screening device is needed to detect patients who have Barrett's esophagus, a precursor to esophageal adenocarcinoma -- the most rapidly increasing cancer in the US. We have developed a prototype instrument based on colorimetric assessment of esophageal lumen. The system consists of a small diameter fiber-optic probe, interfacing electronics, a probe-head position sensor and a computer for display and analysis. The probe has a central plastic optical fiber through which white light is incident on the collapsed esophageal lumen via c conical mirror in the probe-head. A parabolic mirror in the probe-head focuses the reflected light is applied to a linear 520 X 3 RGB photo-diode array to generate proportional electrical signals. A position sensor tracks probe-head location as it is retracted, allowing generation of a 2D colormap of esophageal lumen. A color change from white to red indicates Barrett's esophagus. The system performed accurately in tests using models of esophageal lumen which simulate patterns observed in Barrett's esophagus.

We have investigated the imaging of structural details at various depths within rat brain tissue to better understand the loss of resolution and contrast due in large part to light scattering. A target was imaged through various thicknesses of tissue; the normalized slope of transition between light and dark regions of the images was used as an effective resolution index. The ERI improves dramatically as the wavelength is increased: 0.03 at 600nm, 0.3 at 850nm for a 270 micrometers -thick hippocampus slice. A comparable change was noted for a 270 micrometers -thick cortex slice. For a fixed wavelength, ERI decreases for thicker hippocampus slices, form 0.67 at 220 micrometers to 0.31 at 250 micrometers and to 0.24 at 300 micrometers . Image contrast improves with longer wavelength: from 0.9 at 600nm to 9.5 at 850 nm; from 0.9 at 600nm to 4.6 at 850nm. Despite regional differences in the transparent of brain regions, images were degraded less by scattering at longer wavelengths, arguing strongly for the use of near-IR wavelengths for microscopic imaging either with transmitted light or fluorescent emission for exploring deeper biological structures.

To establish a non-invasive measurement method for human embryo viability, we studied the fiber-optic dynamic viscoelasticity measurement system. We measured the dynamic viscoelasticity of the gelatin gel model by optical monitoring of the displacement, stress and their phase difference. We measured the reflected light power change of the model surface by a single optical fiber to obtain the displacement of the surface. The dimensions of the gelatin cube model were 1 X 1 X 1cm. A He-Ne laser with 632.8nm in wavelength was used as an illumination light source. A thin single optical fiber with 200 micrometers in core diameter was used both for the illumination and detection. A solenoid-actuator was used to vibrate the model. In the surface displacement ranging from 230 micrometers to 400 micrometers , we carried out the linear relation between the reflected light power change and displacement. We measured the dynamic viscoelasticity in gelatin concentration from 2.5 percent to 7.5 percent. Since the dynamic viscoelasticity of the gelatin increased linearly with increasing of the gelatin concentration, the displacement obtained by the reflected light power measurement can be applicable to obtain the dynamic viscoelasticity. We demonstrated that the efficacy of the novel simple non-invasive dynamic viscoelasticity measurement using the thin optical fiber. This system may be applicable to live embryo measurement with minor reconstruction.

Broadband IR radiation detectors have been developed using miniature, inexpensive, mass produced microcantilevers capable of detecting temperature differences as small as 10^-6 K. Microcantilevers made out of semiconductor materials with dimensions of 50 to 200 micrometers long, 10 to 30 micrometers wide and 0.4 to 4 micrometers thick, undergo bending when exposed to IR radiation and can be used either as uncooled photon or thermal detectors. Mounted on a probe 1 mm in diameter a number of microcantilevers can be accommodated in the working channel of existing endoscopes for in vivo proximity focus measurements inside the human body.

In this work, we examine the physics underlying wave propagation in the head to evaluate various ultrasonic transducers for use in a brian injury detection device. The results of measurements of the attenuation coefficient and phase velocity for ultrasonic propagation in samples of brain tissue and skull bone from sheep are presented. The material properties are then used to investigate the propagation of ultrasonic pressure fields in the head. The ultrasound fields for three different transducers are calculated for propagation in a simulated brain/skull model. The model is constructed using speed-of-sound and mass density values of the two tissue types. The impact of the attenuation on the ultrasound fields is then examined. Finally, the relevant points drawn from these discussions are summarized. We hope to minimize the confounding effects of the skull by using sub-MHz ultrasound while maintaining the necessary temporal and spatial resolution to successfully detect injury in the brain.

Remote monitoring of physiologic data from individual high- risk workers distributed over time and space is a considerable challenge. This is often due to an inadequate capability to accurately integrate large amounts of data into usable information in real time. In this report, we have used the vertical and horizontal organization of the 'fireground' as a framework to design a distributed network of sensors. In this system, sensor output is linked through a hierarchical object oriented programing process to accurately interpret physiological data, incorporate these data into a synchronous model and relay processed data, trends and predictions to members of the fire incident command structure. There are several unique aspects to this approach. The first includes a process to account for variability in vital parameter values for each individual's normal physiologic response by including an adaptive network in each data process. This information is used by the model in an iterative process to baseline a 'normal' physiologic response to a given stress for each individual and to detect deviations that indicate dysfunction or a significant insult. The second unique capability of the system orders the information for each user including the subject, local company officers, medical personnel and the incident commanders. Information can be retrieved and used for training exercises and after action analysis. Finally this system can easily be adapted to existing communication and processing links along with incorporating the best parts of current models through the use of object oriented programming techniques. These modern software techniques are well suited to handling multiple data processes independently over time in a distributed network.

A unique solid-state optical sensor configuration has been invented that can serve as a development platform for a host of chemical and biochemical sensors in either gaseous or liquid environments. We present results from measurements from the first adaptation of the device to oxygen sensing via fluorescence quenching and note the distinct advantages over existing electrochemical and more recent fiber-optic methods. The platform technology itself features greatly enhanced energy efficiency, high sensitivity, low-power consumption, ease of miniaturization, low cost, high-volume manufacturability using standard methods, very fast response/recovery profiles, and high reliability. The oxygen sensor embodiment has been demonstrated to operate well over the temperature range from -20 to 50 degrees C, not to be interfered with by other common gases including water vapor at high levels, and capable of response times less than 100 milliseconds.

The virtual human will be a research/simulation environment having an integrated system of biophysical models, data, and advanced computational algorithms. It will have a Web-based interface for easy, rapid access from several points of entry. The virtual human will serve as a platform for national and international users from governments, academia and industry to investigate the widest range of human biological and physical response to stimuli, be they biological, chemical, or physical. This effort will go far beyond the modeling of anatomy to incorporate refined computational models of whole-body processes, using mechanical and electrical tissue properties, and biology from physiology to biochemical information. The platform will respond mechanistically to varied and potentially iterative stimuli that can be visualized multi- dimensionally. This effort is in the formative stage of a several-year process that will lead to a program that is of similar proportion to the human genome, but will be much more computationally intensive. The main purpose of this paper is to communicate our early ideas about the philosophic basis of the program, to identify some of the applications for which the virtual human would be used, to elicit comments, and to provide a basis to identify prospective collaborators.

A novel method for location and characterization of discontinuities in biological system is presented. The method uses electromagnetic waves in the microwave and RF region and a modified algorithm previously used for the estimation of the angle of arrival of radar signals. Results are presented for the case of a skull section backed by porcine brain and the same section backed by a layer of blood backed by porcine brain.

Technology has provided many new tools to assist in the diagnosis of pathologic conditions of the heart. Echocardiography, Ultrafast CT, and MRI are just a few. While these tools are a valuable resource, they are typically too expensive, large and complex in operation for use in rural, homecare, and physician's office settings. Recent advances in computer performance, miniaturization, and acoustic signal processing, have yielded new technologies that when applied to heart sounds can provide low cost screening for pathologic conditions. The short duration and transient nature of these signals requires processing techniques that provide high resolution in both time and frequency. Short-time Fourier transforms, Wigner distributions, and wavelet transforms have been applied to signals form hearts with various pathologic conditions. While no single technique provides the ideal solution, the combination of tools provides a good representation of the acoustic features of the pathologies selected.

The electromagnetic bioimpedance method has successfully measured the very subtle conductivity changes associated with brain edema and prostate tumor. This method provides noninvasive measurements using non-ionizing magnetic fields applied with a small coil that avoids the use of contact electrodes. This paper introduces results from combining a holographic signal processing algorithm and a low power coil system that helps provide the 3D image of impedance contrast that should make the noninvasive electromagnetic bioimpedance method useful in health care.

Medical telesensors are self-contained integrated circuits for measuring and transmitting vital signs over a distance of approximately 1-2 meters. The circuits are unhoused and contain a sensor, signal processing and modulation electronics, a spread-spectrum transmitter, an antenna and a thin-film battery. We report on a body-temperature telesensor, which is sufficiently small to be placed on a tympanic membrane in a child's ear. We also report on a pulse-oximeter telesensor and a micropack receiver/long- range transmitter unit, which receives form a telesensor array and analyzes and re-transmits the vital signs over a longer range. Signal analytics are presented for the pulse oximeter, which is currently in the form of a finger ring. A multichip module is presented as the basic signal-analysis component. The module contains a microprocessor, a field=programmable gate array, memory elements and other components necessary for determining trauma and reporting signals.

NASA is developing miniaturized electrolyte and blood gas sensors to aid investigations into the influence of space flight on physiologic systems. These sensors are being applied in ex vivo blood flow loops as well as in in vivo wireless telemetric configurations. Our development approach is to first implement sensors in simple hand-made miniaturized catheter shaped configurations, and then migrate to micro planar configurations compatible with low- cost mass production. Catheter-based sensors are used for materials performance and biocompatibility testing, and for systems level integration, demonstration, and evaluation. For example, we have shown that pH sensitive polymer membranes cast on miniaturized catheters survive chronic implantation in rat subcutaneous tissue for periods up to 12 weeks with little loss in performance characteristics such as drift, sensitivity, selectivity, and response time. Microfabrication options for electrochemical sensors are based on a combination of thin and thick film technology with inexpensive non-silicon substrates. For the inorganic layers we are working with thin film technology with inexpensive non-silicon substrates. For the inorganic layers we are working with thin film evaporation and silk- screening, and for the organic layers we are comparing drop delivery and silk-screen approaches. The electrochemical cells are contacted from the back-side and each type of sensor is optimized on a separately fabricated substrate. Sensor combinations are then put into any desired array configuration with pick-and-place technology. This modular approach has many advantages over the integrated sensor approach which has been promoted as the ideal sensor solution for many years.

This paper presents a new framework, CVSys, for dynamic and fully distributed cardiovascular simulation with natural behavior flow and dynamic simulation control. This coordination framework uniquely incorporates attributes of open-endedness in terms of dynamic interactive entry of changing states during runtime, flexibility of event handling and system extensibility. The coordination framework relies on the autonomous object paradigm underlying a new distributed computing environment, MESSENGERS.

This paper describes the integrated medical analysis system (IMAS) The evolving system consists of an integrated suite of models and tools providing quantitative and dynamic analysis from multiple physiological function models, clinical care patient input, medical device data, and integrated medical systems. The system is being developed for requirements definition, patient assessment, control theory, training, instrumentation testing and validation. Traditionally, human models and simulations are performed on small scale, isolated problems, usually consisting of detached mathematical models or measurements studies. These systems are not capable of portraying the interactive effects of such systems and certainly are not capable of integrating multiple external entities such as device data, patient data, etc. The human body in and of itself is a complex, integrated system. External monitors, treatments, and medical conditions interact at yet another level. Hence, a highly integrated, interactive simulation system with detailed subsystem models is required for effective quantitative analysis. The current prototype emphasizes cardiovascular, respiratory and thermoregulatory functions with integration of patient device data. Unique system integration of these components is achieved through four facilitators. These facilitators include a distributed interactive computing architecture, application of fluid and structural engineering principles to the models, real-time scientific visualization, and application of strong system integration principles. The IMAS forms a complex analytical tool with emphasis on integration and interaction at multiple levels between components. This unique level of integration and interaction facilitates quantitative analysis for multiple purposes and varying levels of fidelity. An overview of the project and preliminary findings are introduced.

Photon-biased modulator was the novel photon device model based on the complementarily modulated transmission of biological photochrome bacteriorhodopsin (BR) film. BR has two dominant photoactive states during the photocycle, B and M, which have well-separated absorption bands with maxima at 568 nm and 412 nm. The local transmission of a BR film depends on the ratio between the forward and the backward rate constants of photoreactions. The modulatable saturated absorption of chemically enhanced BR film under multi-beam illumination was studied. The theoretical analysis indicated that there exists the threshold intensity for the BR film simultaneously illuminated by two beams at 568 nm and 412 nm. Around threshold intensity, the transmissions of two beams are complementarily modulated. As one of the useful photon device application of photon transistor, new method of incoherent distortionless bright background removal in image processing was presented.

Mag-indo-1 is a well known fluorescent probe. Magnesium complexation results in a shift of the emission fluorescence spectrum from 480 nm to 417 nm with an intensity proportional to the magnesium concentration in the range 0.6 to 30 mM. Although designed as a specific magnesium chelator, Mag-indo-1 is also able to bind calcium and zinc. All these cationic interactions induced the same spectral shift but the fluorescence intensity and the dissociation constant are dependent of the nature of the cation. Furthermore Mag-indo-1 can also bind proteins through a specific interaction with some histidin residues. That interaction induces a characteristic spectral shift of the emission fluorescence spectra from 480 to 457 nM. All these properties suggest that Mag-indo-1 could be used to study the protein-cation binding. Emission and synchronous fluorescence techniques have been used to monitor that interaction with proteins such as bovine serum albumin, human serum albumin, turkey white egg lysozyme. Using a method of resolution of complex fluorescence spectra, it has been possible to calculate the number of interaction sites and the correlative dissociation constants. Depending on the nature of the protein a quenching of the natural fluorescence of the protein was observed, associated with an energy transfer from some tryptophan(s) to Mag-indo-1. All these data were tentatively correlated with the available information on the 3D conformation of the proteins. These results suggest that Mag-indo-1 could be used as an intramolecular fluorescent ruler to monitor the changes in 3D conformation of specific sub-domains of proteins.

Cell is the basic structural and fundamental unit of all organisms; the smallest structure capable of performing all the activities vital to life. One goal of current research interest is to learn how the muscle varies the strength of its contraction in response to electric stimuli. A wide variety of techniques have been developed to monitor the mechanical response of isolated cardiac myocytes. Some success has been reported either with the use of intact rat myocytes supported by suction micropipettes or in guinea pig myocytes adhering to glass beams. However, the usual measuring techniques exhibit destructive contact performance on live cells. They could not solve the problem, since the cell may die during or after the time-consuming attachment process at the beginning of each experiment. In contrast, a novel optical system, which consists of a microglass tube with an inner diameter the same size of a real cardiac cell, is proposed to simulate real cell's twitch process. the physical parameters of synthetic cell are well known. By comparing the dynamics of the real cell with that of the simulated cell, the twitch characteristics of the real cell can be measured.

The changes of diffuse reflected light by tissues with blood pulse circulation as function of external pressure was studied. The experimental measurements were performed with steady state and pulsatile components of the photoplethysmographic signal taken from human finger under compression. Specially designed reflection-mode sensor registered the true waveform of pulse waves. The unexpected change of the pulsatile amplitude from increasing to decreasing with compression was found. To explain this effect a Kubelka-Munk approximation model of a deformable medium with embedded particles of different types and concentrations was developed. On the basis of this model it is shown that the observed optomechanical effect is brought about by a shift of the balance between blood pressure and the external pressure of stressed vessel walls and surrounding media. The results show capability of photoplethysmographic technique to detect very small local tissue stress changes and to measure local vessel wall elasticity.

We report the development of a microspectrophotometer system for use on micro samples of mitochondrial respiratory pigments. A novel optical fiber set-up uses visible spectrophotometry to monitor the reduction of mitochondrial electron carriers. Data is presented for the reduction of cytochrome-c and for the effect of temperature on the levels of complex II/III activity from the mitochondria of rat liver. This in-vivo simulation of the reduction of cytochrome-c can be observed using a fiber optic probe which requires less than twenty (mu) l of sample for analysis. The key features of the system are: front end adaptability, high sensitivity and fast multispectral acquisition which are essential for the biological reactions which are observed.

Existing models of membrane instability and breakdown under an applied voltage are critically examined. An alternative, speculative treatment of the electroelastic model is suggested, based on the assumption that spatial dispersion of the elastic moduli leads to their effective softening at short wave lengths. The model parameters describing this effect chosen to satisfy the condition that softening of the 'peristaltic' mode due to an applied voltage of 1 to 1.5 V leads to instability and breakdown. With these parameters we calculate the stretching diagram of the membrane and show that it agrees with existing measurements.

Fluktuon model micelle formation in which the critical micelle concentration (CMC) formation depended on depth of potential pit forming as a result conformational transformation of the hydrocarbon tails of surfactant molecules has been considered in this work. The qualitative valuations of depth of connected conditions A by the method of Molecular Orbits were received, where the effect of parity in dependence on number of atoms carbon in circuit is observed. For the odd number of atoms A is much more less than with even number of atoms in circuit for conformation of surfactant molecules. Hence, on formula the jumps in dependence's CMC on A should be observed at transition from hydrocarbonic of circuit with parity by number of atoms carbon to odd one. Really, the experiments on measurements CMC for homologies alkilsulphate sodium have shown, that the effect of parity on attitude to number of atoms C was observed with increase of length of the hydrocarbonic tails alkilsulphate sodium.

Mechanism of luminescence of aqueous surfactant solutions has been considered. It is shown that intensity of luminescence non-linearity depended from aggregate size, i.e. in point of micellization intensity of luminescence can serve by reliable method for detection and forecasting carious structural formations in liquid such as biological, micellar, colloidal and etc.

Rare-earth ions, with relatively long luminescence lifetimes, have significant advantages for diagnostic application. In diagnostics the long luminescence lifetimes allow for extremely sensitive time-gated detection, where the difference in temporal behavior of scatter and background fluorescence and the long-lived rare earth luminescence is utilized. Unfortunately the absorption cross-section of rare earth ion transitions is extremely low. However, via sensitized excitation by means of a suitable organic molecule efficient excitation is obtained. It is shown that excitation in the visible part of the spectrum can be used to excite rare-earth ions which luminescent in the near-IR, such as ytterbium, neodymium and erbium, via a fluorescein-derivative as sensitizer. The advantages of this approach are manifold. Low cost light source are available for the visible part of the spectrum and interference's from the matrix are minimal. Detection in the near-IR is almost interference-free.

A new, non-invasive method was developed for identification of blood vessels and monitoring different physiological parameters, based on a specific combination of distance light source-detector, optical wavelength, size and aperture of light source and detector.

The primary goal of these studies was to demonstrate that NIR Raman spectroscopy is feasible as a rapid and reagentless analytic method for clinical diagnostics. Raman spectra were collected on human serum and urine samples using a 785 nm excitation laser and a single-stage holographic spectrometer. A partial east squares method was used to predict the analyte concentrations of interest. The actual concentrations were determined by a standard clinical chemistry. The prediction accuracy of total protein, albumin, triglyceride and glucose in human sera ranged from 1.5 percent to 5 percent which is greatly acceptable for clinical diagnostics. The concentration measurements of acetaminophen, ethanol and codeine inhuman urine have demonstrated the potential of NIR Raman technology in screening of therapeutic drugs and substances of abuse.

The Johns Hopkins University Applied Physics Laboratory (JHU/APL) is designing, fabricating and testing a small, high resolution, time-of-flight mass spectrometer (TOFMS) suitable for biomedical applications requiring lightweight, low-powered and portable instrumentation. This instrument can be used to identify solids, liquids and gases of both chemical and biological origins to quantify the habitat environment and support biomedical research and medical care. The virtue of the JHU/APL TOFMS technology presented here, resides in the promise for a small, lightweight, low- power, device that can be used continuously with advanced signal processing diagnostics. To date, JHU/APL has demonstrated mass capability beyond 10,000 Atomic Mass Units in a very small, low power prototype for biological analysis. The JHU/APL approach, described in this paper, is to design the instrument for both wide mass range and fine mass resolution by the use of electronic control in a tandem mass spectrometer instrument. In this paper we will outline the principle behind the operation of the APL's miniaturized TOFMS system and present examples of the analysis of chemical and biological substances. In addition, we will also describe a novel method for the collection of airborne particles for TOFMS analysis suitable for automated collection and analysis applications.