Optomechanical Medical Devices (Instruments) use lightwaves (UV, Visible, IR) for one or more of the following functions; to observe, to measure, to record, to test (align) and or to cut/repair. The evolution of Optomechanical Medical Devices probably started when the first torch or candle or petrochemical lamp used a polished reflector (possibly with a concave configuration) to examine a part of a patient's body (possibly a wound).Once the glass lens was invented, light sources of any type could be forcussed to increase illuminating power on a selected area. Medical Devices have come a great distance since these early items. Skipping across time to three rather significant inventions and advancements, we are well into the era of Laser and Fiber Optics and Advanced Photodetectors, all being integrated into Medical Devices. The most notable fields have been Ophthalmology, Dermatology, and Surgery. All three fields have been able to incorporate both the use of the Laser and the use of Fiber Optics (and at times the use of Photodetectors), into a single device (instrument). Historical: Philipp Bozzini (a Doctor, maybe) in the early 1800's used a hollow tube (tube material not identified) to project the light of a candle through the tube to view a patient's 'what ever'. Only Philipp, the patient and G-d knows what was being viewed. This ws the first recorded information on what could be considered the very first 'Endoscope examination'

We propose a torsional eye movement measurement method based on the spatial moment analysis of iris pattern image. First the measurement procedure is proposed. Then our proposed method was evaluated by applying it to an eye movement image sequence simulated by our developed three-dimensional eye movement simulator. The results measured by the spatial moment analysis and the method based on stochastic algorithms show that the standard deviation of torsion angle errors for the spatial moment analysis is less than that for the method based on stochastic algorithms. Next, we applied it to an image sequence obtained with the infrared CCD camera. For the comparison, the torsion angles were measured by using the methods based on stochastic algorithms and the cross correlation analysis. The technique based on cross correlation of a sampled iris pattern encircling the pupil is well used in the torsion angle measurement. The results measured by three methods show similarity but the result for the moment analysis resembles that for the cross correlation analysis more closely than that for the method based on stochastic algorithms. The differences between them were around 1degree. From the computational complexity, our proposed spatial moment analysis method becomes a simple torsion angle measurement.

Rapid mixing is essential in many of the micro-fluidic systems targeted for use in the testing of biochip analysis, drug delivery, and analysis or synthesis of blood, among others. A design of a passive micro-mixer is presented in this paper. The mixing is based on the vortex phenomenon of fluid stirring and diffusion. The size of the mixer chip is 10mm×10mm, with a width of the channel of 200μm and a depth of 50μm. This mixer allows fast mixing of small amounts of liquids. A mathematical model that uses gray level contrast to evaluate the mixing efficiency is also proposed. The measurement principle is based on the statistical concept via a quadratic weighting distribution. Experimental results show that the mixing efficiency is over 80% for mixing two liquids with the same polarization and roughly 90% for the mixing of two inks. Thus a new type of biochip can be easily implemented with this system for the application in biomedical diagnostic technology.

The theoretical and the experimental researches of spectra of absent-minded radiation in medium containing viruses were carried out. The information on spectra luminescence 31 viruses was written down.The new method the express - analysis of viruses in organism of the man was developed. It shall be mentioned that the proposed method of express diagnostics allows detection of infection agent in the organism several hours after infection. It makes it suitable for high efficient testing in blood services for detection and rejection of potential donors infected with such viruses as hepatitis, herpes, Epstein-Barre, cytomegalovirus, and immunodeficiency. Methods of serum diagnostics used for that purpose can detect antibodies to virus only 1-3 months after the person has been infected. The device for the express analysis of 31 viruses of the man was created.

A common problem in several surgical applications is the lack of navigational information. Most often, the only source of information about the location of crucial structures, in relation to the surgical instrument, is the visible and tactile sensory input of the surgeon. In some cases, this leads to time-consuming procedures and a high risk for the patient. Therefore, we developed a spectroscopic sensor system for automatic differentiation between several tissue types. For example in milling processes, a sensor that is able to detect bone in contrast to nerve or vein tissue can be used to control the milling process. We showed exemplarily for the cochlea implant, a typical ENT-surgery, that with the help of our sensor system, the milling of bone can be accelerated without increasing the risk for the patient. It is also possible to use this type of sensor system in the area of medical robotics in soft-tissue applications. With real-time information, a continuous registration can take place, in contrast to a registration that is done using static preoperatively acquired images. We showed that our sensor system can be used to dynamically update the location of the patient in relation to CT or MR-images. In conclusion, we have been able to show that well-known spectroscopy sensors can be used to open new possibilities in medical treatment with and without the use of robotics.

This paper presents a low cost semiconductor red laser light delivery system for esophagus cancer treatment. The system is small enough to slide inside the patient’s body and it produces up to 4 Watts of optical power from several semiconductor lasers. Specifically, the paper presents optimized high power 635 nm semiconductor laser array design with testing results. The laser array is more powerful than conventional ridge waveguide and more reliable than the broad area lasers at this wavelength. The design optimization is based on i) thermal analysis using finite element analysis as well as analytical calculations for minimizing laser array temperature, and ii) specially designed scattering elements with nanoparticles, to achieve uniform illumination.

The development of new optical sensor technologies has a major impact on the progress of diagnostic methods. Of the permanently increasing number of non-invasive breath tests, the ¹³C-Urea Breath Test (UBT) for the detection of Helicobacter pylori is the most prominent. However, many recent developments, like the detection of cancer by breath test, go beyond gastroenterological applications. We present a new detection scheme for breath analysis that employs an especially compact and simple set-up. Photoacoustic Spectroscopy (PAS) represents an offset-free technique that allows for short absorption paths and small sample cells. Using a single-frequency diode laser and taking advantage of acoustical resonances of the sample cell, we performed extremely sensitive and selective measurements. The smart data processing method contributes to the extraordinary sensitivity and selectivity as well. Also, the reasonable acquisition cost and low operational cost make this detection scheme attractive for many biomedical applications. The experimental set-up and data processing method, together with exemplary isotope-selective measurements on carbon dioxide, are presented.

In this paper we describe the development of a novel non-invasive multispectral imaging technique, multiphoton photoacoustic spectroscopy (MPPAS). In this technique, a tunable high-power laser is used to perform multiphoton excitation events, which are then detected as an acoustic (i.e. ultrasonic) signal, using a commercial ultrasonic piezoelectric (PZT) transducer. The signal from the PZT is then corrected for laser power fluctuations, resulting in normalized MPPAS signal intensity. Because MPPAS relies on non-radiative relaxation of the absorbing species, unlike single or multiphoton fluorescence spectroscopies, it is capable of monitoring non-fluorescent species. In addition, since the majority of the energy imparted to most molecules upon the absorption of light is released through non-radiative pathways, sensitive measurements of even fluorescent molecules, can be performed. A test solution of aqueous rhodamine 6G was used to obtain the MPPAS spectrum. It matches well with that of the steady state absorbance of the same solution. In addition, concentration dependent studies of rhodamine 6G have shown that the technique is even sensitive to nanomolar concentrations and below.

The determination of optical properties of turbid, absorbing media is of increasing interest in both reseach and industry. In order to estimate the optical properties from steady-state diffuse reflectance measurements sophisticaed analytical models have been introduced. These models, which are based on diffusion approximation, properly explain the diffuse reflectance of low absorbing media in the so-called asymptotic region, which means some mean free paths away from strong sources. It should be noted however, the nearer the sourcea nd the stronger the medium absorbs, the accuracy of these models decrease rapidly. For high spatial resolution, i.e. the use of a small oprical probe, the restriction on the asymptotic region becomes crucial. This restriction can be overcome by means of Monte Carlo simulations, which are not confined to low absorption and the asymptotic region. Given an experimental set-up, i.e. given the radius and the direction of the incident pencil beam and the shape of the collection area, the reflectance can be simulated. Thus a numerical model can be established relating the input parameters - anisotrophy factor, absorption and scattering coefficient - to the diffuse reflectance according to the Monte Carlo simulations. The advantages of this numerical model are a large area of validity in respect of anisotrophy factor, amount of absorption and source distance, and the possibility to adapt the model easily to an even more complex experimental set-up.

Biomechanics place huge challenges on existing measurement technologies for determining the mechanical properties of these materials, as well as just measuring the full-field displacement and strain of these materials. 3D Image Correlation Photogrammetry is proving to be a powerful tool for these measurements, providing full-field 3D measurement of the specimens under normal loadings, even at high-speed. This optical technique is independent of the material that it is measuring, providing a non-contact measurement of any material or geometry type. The results are then directly comparable to finite element models for model verification, iteration and boundary condition determination. This paper discusses the theory of the technology, and its application in deformation and strain measurement of real biomechanic applications, from tissues and organs to ligaments and bones.

This paper describes a software system currently being developed at Clemson University in which a client provides recently obtained data to a remote server running a compute-intensive algorithm. To improve performance and speed up delivery of the results, the server distributes the data among multiple sub-server processors and assembles partial output from each processor into a coherent whole before sending the final results to the client. To demonstrate the capabilities of the system, a specific application is presented in this paper: a fluorescence image reconstruction system for breast cancer detection. An experimental instrument optically scans the patient’s breast and generates some files of experimental data which are then sent to the server via the web. The data is processed by the numerical finite-element based algorithm running in parallel on a server and several sub-servers at Clemson. The algorithm is based on a set of coupled diffusion equations which are used to describe the propagation of excitation and fluorescent emission light in multiply scattering media (such as a breast). The algorithm reconstructs the fluorescence image of the breast in parallel. The resulting fluorescence lifetime and quantum yield mapping data can be sent back to the doctor for image display and analysis. This paper describes the numerical algorithm briefly and the software system which uses Java servlets to collect the data from the client and remote method invocation (Java RMI) to distribute the data to multiple processors. The output of the numerical algorithm, combined with the corresponding finite element mesh information, are input into a mathematical software package called Matlab which is used to produce the final images. Experiments are performed using indocyanine green (ICG) dye and tissue-like phantoms in both single- and multi-target configurations. Phantom experimental results of both lifetime and quantum yield are shown in this paper. Future work includes a refinement of the algorithm to incorporate adaptive mesh techniques. The expectation is that such techniques will improve the accuracy of the reconstructed images.

Benzene is determined by a biosensor based on human kidney tissue as biological component. Dioxygenase catalyse substrate oxidation. The useful analytical range results to be complementary to that of one or more traditional models based on Pseudomonas. The biosensors has got an other aim as its functioning is able to clear up the degradation pathways of benzene. The behavior of a biosensor based on cancerous human kidney tissue compared to healthy one let to hypothize a poor activity of dioxygenase in cancerous kidney, possibly to be tested with prevention strategy.

Pulsed Electrochemical Detection (PED) is a revolutionary approach to the simple, sensitive, and direct detection of numerous polar aliphatic compounds, especially carbohydrates. This technique exploits the electrocatalytic activity of noble metal electrode surfaces to oxidize various polar functional groups. In PED, multi-step potential-time waveforms at Au and Pt electrodes realize amperometric/coulometric detection while maintaining uniform and reproducible electrode activity. The response mechanisms in PED are dominated by the surface properties of the electrode, and, as a consequence, members of each chemical class of compounds produce virtually identical voltammetric responses. Thus, the full potential is realized when combined with high performance liquid chromatography (HPLC). This paper reviews the fundamental aspects of PED and details a novel approach to the chemical "fingerprinting" of natural products. Applications include the characterization of tobacco, peptones, and bacteria.

Multichannel images of 11-Mercaptoundecanoic acid and 11-Mercapto-1-undecanol self-assembled monolayers (SAMs) together with a biospecific interferon-gamma (IFN-gamma)/anti-IFN-gamma antibody immunoreaction were observed by two-dimensional surface plasmon resonance (2D-SPR) imaging system. Patterning process for SAM was simplified by exploiting direct photooxidation of thiol bonding (photolysis) instead of conventional photolithography. Sharper images were resolved by using a white light source in combination with a narrow bandpass filter, minimizing the diffraction patterns on the images. The line profile calibration of the image contrast caused by different resonance conditions at each points on the sensor surface enabled us to discriminate the monolayer thickness in a sub-nanometer scale. For protein patterning, a precipitation scheme induced by biocatalytic reaction was implied for the signal amplification. Specific binding of IFN-gamma antigen with surface-immobilized antibody was found detectable down to the concentration of 1 ng/mL.

An in vitro sensor to detect cardiac markers at less than 2ng/mL and in less than 5 minutes has been achieved. This fiber optic based Surface Plasmon Resonance (SPR) sensor is being applied to detect myoglobin and cardiac Troponin I. Early detection of the onset of myocardial infarction (MI) will greatly enhance the patient care. Myoglobin (MG) and cardiac Troponin I (cTnI) are two biological markers released after a MI. The detection at biologically relevant levels can be diagnostic of MI. Antibodies specific to the antigen of interest are attached to a carboxymethylated dextran (CM-dextran) gold SPR surface. With the method developed, the detection limit for MG is lower than 5ng/mL when detected at 25°C. For cTnI, a detection limit of less than 2ng/mL was achieved in the preliminary tests. For MG, the reaction conditions for antibody attachment of pH 5-6 and a temperature of 37°C gave the highest sensitivity to MG. At pH 6 and 37°C reaction conditions for the antibody attachment were optimal for cTnI. The CM-dextran chain length also influences the antibody loading on the surface: longer CM-dextran chain gives a higher sensitivity to cTnI. The sensor fouls when in contact with serum. Replacing CM-dextran with different biocompatible polymers greatly improve the sensor performance in serum.

Traditional cancer treatment, surgical removal and gamma- or x-ray irradiation, is often augmented by the use of chemotherapy drugs. Theses drugs prevent cancer cell growth through a variety of biochemical mechanisms, but are not target specific and kill other cells. Consequently, the amount administered has a narrow range of safe and effective use. Furthermore, because of the dangerous side-effects of these drugs, clinical trials can not be performed, and a statistical basis for dosage is not available. Instead, the concentration of the drugs and their metabolites are monitored during treatment of cancer patients, Unfortunately current practices require 10-20 mL of blood per analysis, and multiple samples to profile pharmacokinetics may further jeopardize the patient's health. Saliva analysis has long been considered an attractive alternative, but the large sample volumes are difficult to obtain. In an effort to overcome this limitation we have been investigating metal-doped sol-gels to both separate drugs and their metabolites from saliva and generate surface-enhanced Raman spectra. We have incorporated the sol-gel in a disposable pipette format, and generally no more than two drops (100 μL) of sample are required. The detailed molecular vibrational information allows chemical identification, while the increase in Raman scattering by four to six orders of magnitude allows detection of nanomolar concentrations. Preliminary measurements will be presented.

Surface enhanced Raman scattering (SERS) is an extremely sensitive and selective spectroscopic technique commonly employed for trace environmental analyses. We are currently developing and optimizing novel SERS based immuno-nanosensors for the monitoring of protein expression within individual living cells. These sensors, based upon antibody bound, silver coated silica nanospheres, can be inserted into individual cells and non-invasively positioned to the subcellular location of interest using optical tweezers. Because a HeNe laser is used for excitation, both photodamage to cells and cellular autofluorescence are minimized. Fabrication of the nanosensors is performed by first depositing a thin layer of silver on silica nanospheres by either homogeneous chemical deposition or vapor deposition. This is followed by binding an antibody against the analyte of interest to the sensor’s surface. In this paper we have investigated and optimized the reduction conditions of a chemical deposition substrate fabrication method and have compared these substrates to three types of vapor deposited substrates: (1) single layer silver film over nanosphere (SFON), (2) dual layer silver film over nanosphere (DUAL-FON) substrates (produced by coating an additional layer of silver film over the SFON), and (3) multilayer silver film over nanosphere (MULTI-FON) substrates (prepared by repeated coatings of several silver films over a SFON). In the case of chemical deposition, parameters optimized included silver nitrate concentration, reaction temperature, and silver coating time of substrates. In general, we have found SFON substrates yield better signal-to-noise ratios (S/N) with less background than the optimized, chemically prepared substrates. Even greater SERS enhancements have been found using multilayered SERS substrates (i.e., DUAL-FON substrates and MULTI-FON substrates). Both the stability and S/N of these substrates are enhanced by using multiple silver layers compared to SFON substrates of similar thickness. From this work, SERS signal enhancements of over an order of magnitude can be predicted by combining the enhancements obtained from the multilayered geometry and that from optimized silver deposition parameters. This paper includes investigations into the mechanism of multi-layer enhancement by studying the SERS S/N changes after different amount of exposure time of underlayer silver films to air. From these studies, we suggest that silver oxide layers play an important role in this multilayered enhancement. To the best of our knowledge, this paper is the first report of this type of silver oxide layer production affecting and even enhancing the resulting SERS signals from continuous film SERS substrates. In this paper, the fabrication, characterization and comparison of these SERS substrates in terms of enhancement factor, and lifetime will be discussed.

The self-assembling and controlled synthesis properties of vertically-aligned carbon nanofibers (VACNF) have been exploited to provide parallel subcellular and molecular-scale probes for biological manipulation and monitoring. VACNFs possess many attributes that make them very attractive for implementation as functional, nanoscale features of microfabricated devices. For example, they can be synthesized at precise locations upon a substrate, can be grown many microns long, and feature sharp, nano-dimensioned tips. They also exhibit characteristic electrochemical responses similar to conventionally studied materials such as the edge plane of pyrolytic graphite and surface-activated glassy carbon. This, and their needlelike, vertical orientation upon a substrate, makes them particularly attractive as multielement cellular scale probes or as a parallel embodiment of traditional single-point microinjection or microelectrophysiological systems. We will overview our efforts at fabricating and characterizing several embodiments of VACNF cell probing systems. We will also overview surface modification techniques that exploit the rich surface chemistries of VACNF arrays to allow immobilization of active enzymes and transcriptionally active DNA, which can provide sensitivity to specific biological analytes and application of the nanofiber architecture for controlled biochemical manipulation within the cell. Finally, we will overview our techniques of integrating these probing structures with intact cells and how these structures may be used on a massively parallel basis for measurement and control of the intracellular domain.

A novel methodology has been developed for the investigation of bacterial spores. Specifically, this method has been used to probe the spore coat composition of two different Bacillus stearothermophilus variants. This technique may be useful in many applications; most notably, development of novel detection schemes toward potentially harmful bacteria. This method would also be useful as an ancillary environmental monitoring system where sterility is of importance (i.e., food preparation areas as well as invasive and minimally invasive medical applications). This unique detection scheme is based on the near-infrared (NIR) Surface-Enhanced-Raman- Scattering (SERS) from single, optically trapped, bacterial spores. The SERS spectra of bacterial spores in aqueous media have been measured using SERS substrates based on ~60-nm diameter gold colloids bound to 3-Aminopropyltriethoxysilane derivatized glass. The light from a 787-nm laser diode was used to trap/manipulate as well as simultaneously excite the SERS of an individual bacterial spore. The collected SERS spectra were examined for uniqueness and the applicability of this technique for the strain discrimination of Bacillus stearothermophilus spores. Comparison of normal Raman and SERS spectra reveal not only an enhancement of the normal Raman spectral features but also the appearance of spectral features absent in the normal Raman spectrum.

The important problem of modern laser medicine is the decrease of an exposure of biological tissues outside of an operational field and can be solved by optical radiation limiting. Organic dyes with reversibly darkening can be placed onto surfaces of irradiated tissues or can be introduced in solder for laser welding of vessels. The limiting properties of a set of nontoxic organic compounds were investigated. Nonlinear optical properties of dyes having reverse saturable absorption (pyran styryl derivatives, cyanine and porphyrine compounds) were studied under XeCl and YAG:Nd (II harmonics) lasers excitation. The effect of attenuation of a visible laser radiation is obtained for ethanol solutions of cyanines: radiation attenuation coefficient ( AC) = 25-35 at N/S = 100-250 MW/cm². In water solutions of such compounds in UV spectrum range AC ≈ 10. The spectral characteristics of compounds appeared expedient enough to operational use in laser limiters (broad passband in visible range of a spectrum). Under the data of Z-scanning (the scheme F/10) value AC ≈ 70 was reached. The limiting of power laser radiation in visible (λ = 532 nm) and UV- (λ = 308 nm) spectral region and nanosecond pulse duration (7 -13 ns) across porphyrine solutions and their complexes with some metals (13 compounds) was investigated too. The comparative study of optical limiting dependence on intensity of laser radiation, solvent type and concentration of solutions was carried out for selecte wavelength. There was shown a possible use of pyran styryl derivatives DCM as limiters of visual laser radiation. To understand a mechanism of laser radiation limitation the light induced processes were experimentally and theoretically studied in organic molecules. The quantum-chemical investigation of one cyanine compound was carried out. There were noted the perspectives of laser radiation limiting by application of inverted schemes of traditional laser shutters. Usage of phenomena of light -induced opalescence in one-component liquids and spinodal decay in stratifying liquid solutions is proposed.

Surface plasmon resonance (SPR) imaging is a versatile technique for detection, quantification, and visualization of bio-molecular binding events which have spatial structure. In this paper, we describe the design principles which we are applying toward construction of a new high-performance SPR imager. We briefly review the basic principles of SPR biosensing and SPR imaging, and discuss the goals for the new design. We focus on two main goals, refractive index (RI) resolution and mechanical simplicity. We address RI resolution as a signal-to-noise issue, using simulations to determine how to maximize the signal (i.e. changes in intensity due to binding events) and minimize the noise. Specific attention is paid to the dominant effects of shot noise. Design concepts for collimating and imaging optics which reduce or eliminate the need for mechanical adjustment are presented. Ray-tracing analysis of the collimating optics is used for detailed analysis of collimator performance.