Nanoliter serum sample analysis by mid-infrared spectroscopy for minimally invasive blood-glucose monitoring

The aim of this study was to demonstrate that mid-infrared spectroscopy is able to quantify glucose in a serum matrix with sample volumes well below 1 muL. For this, we applied mid-infrared attenuated total reflectance (ATR) or transmission-based spectroscopic methods to glucose quantification in microsamples of dry-film sera, either undiluted or diluted 10 times in distilled water. The sample series spanned physiological glucose concentrations between 50 and 600 mg/dL and volumes of 80, 8, and 1 nL. Calibration was carried out using multivariate partial least-squares (PLS) modeling with spectral data between 1180 and 940 cm(-1). Best performance was achieved in the ATR experiments. For raw ATR spectra, the optimum standard error of prediction (SEP) of 13.3 mg/dL was obtained for the 8 nL sample series with subsequent 10-fold dilution. With respect to the coefficient of variation of the glucose assay, CV(pred), we obtained a value of 3% for the 80 nL volume samples with spectral preprocessing using matrix protein absorption bands as an internal standard, 4% for the 8 nL samples, and 6% for the 1 nL samples with raw data. Spectral standardization resulted in significant improvement, especially for the 80 nL volume sample series. By contrast, the accuracy of the glucose assay for the 1 nL sample volume series could not be improved either by internal standardization or by considering the dry film areas for normalization, which we attribute to varying topographies of the dry films.     

Injectable biomaterials for minimally invasive orthopedic treatments

Biodegradable and injectable hydroxy terminated-poly propylene fumarate (HT-PPF) bone cement was developed. The injectable formulation consisting HT-PPF and comonomer, n-vinyl pyrrolidone, calcium phosphate filler, free radical catalyst, accelerator and radiopaque agent sets rapidly to hard mass with low exothermic temperature. The candidate bone cement attains mechanical strength more than the required compressive strength of 5 MPa and compressive modulus 50 MPa. The candidate bone cement resin elicits cell adhesion and cytoplasmic spreading of osteoblast cells. The cured bone cement does not induce intracutaneous irritation and skin sensitization. The candidate bone cement is tissue compatible without eliciting any adverse tissue reactions. The candidate bone cement is osteoconductive and inductive and allow osteointegration and bone remodeling. HT-PPF bone cement is candidate bone cement for minimally invasive radiological procedures for the treatment of bone diseases and spinal compression fractures.     

Characterization of glucose microsensors for intracellular measurements.

Ultrasmall glucose sensors have been constructed by using platinum-deposited carbon ring microelectrodes with glucose oxidase. Response times as low as 270 ms have been obtained with these sensors. Moreover, there is a linear relationship between sensor tip diameter and response times. The use of these sensors has been demonstrated in the detection of glucose in single-cell cytoplasm of the large dopamine cell of the pond snail Planorbis corneus. Current responses obtained at these sensors implanted into a cell increase following injection of 2 pL of glucose solution (3 M) into the cell. Results obtained from these experiments show that these sensors are suitable for glucose monitoring in ultrasmall environments. In addition, characterizations of these sensors have been investigated under different O2 concentrations. At atmospheric oxygen concentrations, glucose levels in the submillimolar range can be measured without oxygen interference; however, oxygen interference can be substantial at low oxygen concentrations.     

Ultrahigh-sensitive tin-oxide microsensors for H/sub 2/S detection

Ultrahigh-sensitivity SnO/sub 2/-CuO sensors were fabricated on Si(100) substrates for detection of low concentrations of hydrogen sulfide. The sensing material was spin coated over platinum electrodes with a thickness of 300 nm applying a sol-gel process. The SnO/sub 2/-based sensors doped with copper oxide were prepared by adding various amounts of Cu(NO/sub 3/)/sub 2/.3H/sub 2/O to a sol suspension. Conductivity measurements of the sensors annealed at different temperatures have been carried out in dry air and in the presence of 100 ppb to 10-ppm H/sub 2/S. The nanocrystalline SnO/sub 2/-CuO thin films showed excellent sensing characteristics upon exposure to low concentrations of H/sub 2/S below 1 ppm. The 5% CuO-doped sensor having an average grain size of 20 nm exhibits a high sensitivity of 2.15/spl times/10/sup 6/ (R/sub a//R/sub g/) for 10-ppm H/sub 2/S at a temperature of 85/spl deg/C. By raising the operating temperature to 170/spl deg/C, a high sensitivity of /spl sim/10/sup 5/ is measured and response and recovery times drop to less than 2 min and 15 s, respectively. Selectivity of the sensing material was studied toward various concentrations of CO, CH/sub 4/, H/sub 2/, and ethanol. SEM, XRD, and TEM analyses were used to investigate surface morphology and crystallinity of SnO/sub 2/ films.     

Design of microsensors for pressure measurement

Establishing a standard methodology for the design of microsensors is a fairly formidable task, in light of the wide range of design and fabrication methods that exist. These methods differ in particular in the material and method of production of the sensing element. An integrated method of microsensor design is presented in this article on the basis of an analysis of the literature data and special experiments conducted for that purpose. Translated from Izmeritel'naya Tekhnika, No. 12, pp. 20–22, December, 1997.     

Analytical solutions of sensitivity for pressure microsensors

Pressure microsensors are normally designed in linear operation range. In this study, analytical solutions are presented in order to offer a set of simple equations to designers and researchers to calculate and predict the sensitivity of pressure microsensors. The pressure sensitivity is proportional to the square of the ratio of diaphragm thickness to diaphragm length, but it is inversely proportional to burst pressure. We found that the analytical solutions are in good agreement with simulation by finite element method     

Monitoring glutamate and ascorbate in the extracellular space of brain tissue with electrochemical microsensors

This paper describes electrochemical microsensors for the in vivo measurement of glutamate and ascorbate in the extracellular space of brain tissue. To prepare glutamate microsensors, carbon fiber microelectrodes (10 microns in diameter and 300-400 microns long) were modified with a cross-linked redox polymer film containing enzymes. The microsensors were coated with a thin Nafion film before use. The glutamate microsensors were both selective and sensitive toward glutamate, with detection limits in the low micromolar range. Physiologically relevant concentrations of several electroactive compounds found in brain tissue produced no response at the glutamate microsensors and also did not affect their glutamate response, the only exception being glutamine, for which a small response was observed in the absence, but not in the presence, of glutamate. The ascorbate microsensors were used in conjunction with cyclic voltammetry. They were sensitive and selective toward ascorbate, but did exhibit a small sensitivity toward the dopamine metabolite, dihydroxyphenylacetic acid. The in vivo measurements performed establish the ability of the glutamate microsensors to monitor the component of the basal extracellular glutamate level that is derived from the neuronal activity of brain tissue.     

Characterization of a near-infrared laparoscopic hyperspectral imaging system for minimally invasive surgery

We developed and characterized a new imaging platform for minimally invasive surgical venues, specifically a system to help guide laparoscopic surgeons to visualize biliary anatomy. This platform is a novel combination of a near-infrared hyperspectral imaging system coupled with a conventional surgical laparoscope. Intraoperative tissues are illuminated by optical fibers arranged in a ring around a center-mounted relay lens collecting back-reflected light from tissues to the hyperspectral imaging system. The system consists of a focal plane array (FPA) and a liquid crystal tunable filter, which is continuously tunable in the near-infrared spectral range of 650-1100 nm with the capability of passing light with a mean bandwidth of 6.95 nm, and the FPA is a high-sensitivity back-illuminated, deep depleted charge-coupled device. Placing a standard resolution target 5.1 cm from the distal end of the laparoscope, a typical intraoperative working distance, produced a 7.6-cm-diameter field of view with an optimal spatial resolution of 0.24 mm. In addition, the system's spatial and spectral resolution and its wavelength tuning accuracy are characterized. The spectroscopic images are formatted into a three-dimensional hyperspectral image cube and processed using principle component analysis. The processed images provide contrast based on measured spectra associated with chemically different anatomical structures helping identify the main molecular chromophores inherent to each tissue. The principal component images were found to image swine gallbladder and biliary structures from surrounding tissues, in real time, during cholecystectomy surgery. Furthermore, it is shown that surgeons can interrogate selected image subregions for their molecular composition identifying biliary anatomy during surgery and before any invasive action is undertaken.     

Pt-modified carbon nanotube networked layers for enhanced gas microsensors

Carbon nanotubes (CNTs) networked films have been grown by chemical vapor deposition (CVD) technology onto miniaturized low-cost alumina substrates, coated by nanosized Co-catalyst for growing CNTs, to perform chemical detection of toxic gasses (NO₂ and NH₃), greenhouse gasses (CO₂ and CH₄) and domestic safety gasses (CO and C₂H₅OH) at an operating sensor temperature of 120 °C. The morphology and structure of the CNTs networks have been characterized by scanning electron microscopy (SEM). A dense network of bundles of multiple tubes consisting of multi-walled carbon nanostructures appears with a maximum length of 1-5 μm and single-tube diameter varying in the range of 5-40 nm. Surface modifications of the CNTs networks with sputtered Platinum (Pt) nanoclusters, at tuned loading of 8, 15 and 30 nm, provide higher sensitivity for significantly enhanced gas detection compared to un-decorated CNTs. This could be caused by a spillover of the targeted gas molecules onto Pt-catalyst surface with a chemical gating into CNTs layers. The measured electrical conductance of the functionalized CNTs upon exposures of a given oxidizing and reducing gas is modulated by a charge transfer model with p-type semiconducting characteristics. The effect of activated carbons as chemical filters to reduce the influence of the domestic interfering alcohols on CO gas detection has been studied. Functionalized CNT gas sensors exhibited better performances compared to unmodified CNTs, making them highly promising candidates for functional applications of gas control and alarms.     

Thermo-optic design for microwave and millimeter-wave electromagnetic power microsensors

Rendina et al. recently proposed the original configuration of an electromagnetic power sensor for microwaves and millimeter waves that is based on an optically interrogated all-silicon chip [Electron. Lett. 35, 1748 (1999)]. Here we theoretically analyze and discuss in detail the performances of such a new class of nonperturbing and wideband probe in terms of sensitivity, resolution, intrinsic detectivity, linearity, and response time. Good agreement between theory and experiments is demonstrated. In particular, minimum resolutions of approximately 1 mW/cm2 are obtained at frequencies beyond 10 GHz. The dependence of response on the geometrical and electromagnetic parameters of the sensing element is analyzed, and on this basis the possibility of achieving optimized configurations is discussed.     

A minimally invasive method to evaluate 131I kinetics in blood

The dose limiting factor for 131I therapy in patients with thyroid cancer is myelotoxicity, thus an accurate determination of radioiodine activity in the red marrow is of paramount importance. The reference method for red marrow dosimetry in radiometabolic therapy is based on the measurement of radioiodine kinetics, particularly the activity/time curve in blood. Such a measurement requires withdrawal of blood samples at various times after 131I administration. This procedure involves some potential risk from the radiation protection point of view, such as possible contamination of personnel with blood and disposal of the radioactive blood samples (and syringes). We present here a minimally invasive method to evaluate radioiodine kinetics in the blood, which only requires one blood sample and a set of measurements on the patient's thigh made with a collimated NaI(Tl) probe. The method has been validated in four patients treated with 131I for thyroid cancer.     

Vapor recognition with small arrays of polymer-coated microsensors. A comprehensive analysis.

A comprehensive analysis of vapor recognition as a function of the number of sensors in a vapor-sensor array is presented. Responses to 16 organic vapors collected from six polymer-coated surface acoustic wave (SAW) sensors were used in Monte Carlo simulations coupled with pattern recognition analyses to derive statistical estimates of vapor recognition rates as a function of the number of sensors in the array (< or = 6), the polymer sensor coatings employed, and the number and concentration of vapors being analyzed. Results indicate that as few as two sensors can recognize individual vapors from a set of 16 possibilities with < 6% average recognition error, as long as the vapor concentrations are > 5 x LOD for the array. At lower concentrations, a minimum of three sensors is required, but arrays of 3-6 sensors provide comparable results. Analyses also revealed that individual-vapor recognition hinges more on the similarity of the vapor response patterns than on the total number of possible vapors considered. Vapor mixtures were also analyzed for specific 2-, 3-, 4-, 5-, and 6-vapor subsets where all possible combinations of vapors within each subset were considered simultaneously. Excellent recognition rates were obtainable for mixtures of up to four vapors using the same number of sensors as vapors in the subset. Lower recognition rates were generally observed for mixtures that included structurally homologous vapors. Acceptable recognition rates could not be obtained for the 5- and 6-vapor subsets examined, due, apparently, to the large number of vapor combinations considered (i.e., 31 and 63, respectively). Importantly, increasing the number of sensors in the array did not improve performance significantly for any of the mixture analyses, suggesting that for SAW sensors and other sensors whose responses rely on equilibrium vapor-polymer partitioning, large arrays are not necessary for accurate vapor recognition and quantification.     

Harsh environments minimally invasive optical sensor using free-space targeted single-crystal silicon carbide

To the best of our knowledge, for the first time, a single-crystal silicon carbide (SiC)-based minimally invasive smart optical sensor suited for harsh environments has been designed and demonstrated. The novel sensor design is based on an agile wavelength source, instantaneous single-wavelength strong two-beam interferometry, full optical power cycle data acquisition, free-space targeted laser beams, multiple single-crystal-thick SiC optical front-end chips, and multiwavelength signal processing for unambiguous temperature measurements to form a fast and distributed smart optical sensor system. Experiments conducted using a 1550-nm eye-safe band-tunable laser and a 300-/spl mu/m coating-free thick SiC chip demonstrate temperature sensing from room temperature to 1000/spl deg/C with an estimated average 1.3/spl deg/C resolution. Applications for the proposed sensor include use in fossil fuel-based power systems, aerospace/aircraft systems, satellite systems, deep-space exploration systems, and drilling and oil mining industries.     

An electrochemical method for making enzyme microsensors. Application to the detection of dopamine and glutamate

A novel method of microbiosensor fabrication is described. It is based on the electrochemical polymerization of an enzyme-amphiphilic pyrroleammonium solution on the surface of a microelectrode in the absence of supporting electrolyte. By trapping glutamate oxidase (GMO) or polyphenol oxidase (PPO) in such polypyrrole films, we made microbiosensors for the amperometric determination of glutamate or dopamine, respectively. The response of the GMO microelectrode to glutamate was based on the amperometric detection of the enzymically generated hydrogen peroxide at 0.6 V vs SCE. The detection limit and sensitivity of this microbiosensor were 1 μM and 32 mA M(-1) cm(-2), respectively. The response of the PPO microelectrode to dopamine was based on the amperometric detection of the enzymically generated quinoid product at -0.2 V. The calibration range for dopamine measurement was 5 × 10(-8)-8 × 10(-5) M and the detection limit and sensitivity were 5 × 10(-8) M and 59 mA M(-1) cm(-2), respectively.     

Mictomagnetism in a new BaO.Fe2O3.B2O3 glass.

An homogeneous BaO ·Fe₂O₃ ·B₂O₃ glass containing 30% Fe₂O₃ is prepared by a splat-cooling technique. X-ray and electron diffraction reveal the product to be amorphous at room temperature. The crystallization, as shown by DTA studies, begins at 750 K, and up to 950 K, a temperature at which BaFe₁₂O₁₉ is shown to be present, the crystallizing products are mainly evolutive.The magnetic measurements show a probably mictomagnetic behaviour at low temperature with a maximum of magnetic susceptibility at 12 (±1) K. At higher temperature the susceptibility obeys a Curie-Weiss law with large negative Weiss constant and low Curie constant per Fe³⁺ ions. After crystallization the product is ferrimagnetic and could be used as a permanent magnet.Mössbauer study reveals that the glass mainly consists of Fe³⁺ ions in distorted sites and a hyperfine structure at low temperature; the magnetic ordering temperature is estimated to be about 44 (±1) K.     

矫形外科微创手术与导航技术研究进展

矫形外科手术导航技术是矫形外科手术微创化的基础技术之一,医生通过手术导航系统可以进行术前的手术规划和手术方案模拟,还可以进行术中的手术监视和干涉,从而保证了医生方便、快捷、高效地完成各种复杂手术。本文综述了矫形外科手术特点和导航技术的最新发展,分析了导航系统的功能和系统组成,从医学图像、定位技术、系统配准的角度介绍了矫形外科导航系统的特点,为我国矫形外科导航手术的发展提供了借鉴和参考。     

A.c. conductivity for amorphous TeO2-P2O5 glass system

The a.c. conductivity for the TeO₂-P₂O₅ glassy system was measured in the temperature range 300–573 K and in the frequency range 100 Hz to 10 kHz. The a.c. conductivity () increased with frequency according to the relation ()^s. The frequency exponent s was found to decrease with increasing temperature. The composition dependence of the conductivity was also investigated. The density of states was also calculated using the Elliott model. The a.c. conductivity increased over the studied temperature range. The obtained experimental data have been analysed with reference to various theoretical models. The analysis shows that the correlated barrier hopping (CBH) model is the most appropriate mechanism for conduction in the TeO₂-P₂O₅ glass system.     

Speckle-contrast monitoring of tissue thermal modification

Measurements of the contrast value of time-averaged speckle-modulated images of cartilage tissue are used to study tissue thermal modification in the case of laser-light treatment. This modification is related to thermally induced internal stress relaxation in the matrix of the treated tissue. The specific feature of the evolution of time-averaged speckle contrast with a change in the current temperature of modified collagen tissue is the typical looplike form of the contrast-temperature dependencies associated with irreversible changes in tissue structure and correlated with changes in the tissue diffuse transmittance and the tissue internal stress mentioned by other researchers.