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Biomedical subjects

Joseph T Walsh

Publications and source records attributed to Joseph T Walsh.

16 recordsLinked to original sources

In vivo glucose measurement by surface-enhanced Raman spectroscopy.

This paper presents the first in vivo application of surface-enhanced Raman scattering (SERS). SERS was used to obtain quantitative in vivo glucose measurements from an animal model. Silver film over nanosphere surfaces were functionalized with a two-component self-assembled monolayer, and subcutaneously implanted in a Sprague-Dawley rat such that the glucose concentration of the interstitial fluid could be measured by spectroscopically addressing the sensor through an optical window. The sensor had relatively low error (RMSEC = 7.46 mg/dL (0.41 mM) and RMSEP = 53.42 mg/dL (2.97 mM).

Animals↗

Laser stimulation of the auditory nerve.

BACKGROUND AND OBJECTIVES: For centuries, electric current has been used to stimulate neurons. Shortcomings of electrical stimulation include the contact between the stimulating electrode and the tissue, and the non-selective stimulation of the tissue. In contrast to electric stimulation, optical radiation can provide spatially selective neural stimulation without tissue contact. STUDY DESIGN/MATERIALS AND METHODS: Acute in vivo experiments using gerbils were conducted to record optically evoked compound action potentials (CAPs) from the cochlea. RESULTS: Optical radiation evokes CAPs in normal hearing animals and in deafened animals, in which cochleae lack outer and inner hair cells. Stimulation threshold was measured as 0.018+/-0.003 J/cm(2) (mean+/-SE). Laser radiation could be increased by 30-40 dB until drastic changes were seen in cochlear function. Cochlear response amplitudes to optical radiation were stable over extended stimulation times. CONCLUSIONS: We have demonstrated that the auditory nerve can be stimulated by optical radiation. One potential clinical use of this technology would be for cochlear implants.

Animals↗

Real-time glucose sensing by surface-enhanced Raman spectroscopy in bovine plasma facilitated by a mixed decanethiol/mercaptohexanol partition layer.

A new, mixed decanethiol (DT)/mercaptohexanol (MH) partition layer with dramatically improved properties has been developed for glucose sensing by surface-enhanced Raman spectroscopy. This work represents significant progress toward our long-term goal of a minimally invasive, continuous, reusable glucose sensor. The DT/MH-functionalized surface has greater temporal stability, demonstrates rapid, reversible partitioning and departitioning, and is simpler to control compared to the tri(ethylene glycol) monolayer used previously. The data herein show that this DT/MH-functionalized surface is stable for at least 10 days in bovine plasma. Reversibility is demonstrated by exposing the sensor alternately to 0 and 100 mM aqueous glucose solutions (pH approximately 7). The difference spectra show that complete partitioning and departitioning occur. Furthermore, physiological levels of glucose in two complex media were quantified using multivariate analysis. In the first system, the sensor is exposed to a solution consisting of water with 1 mM lactate and 2.5 mM urea. The root-mean-squared error of prediction (RMSEP) is 92.17 mg/dL (5.12 mM) with 87% of the validation points falling within the A and B range of the Clarke error grid. In the second, more complex system, glucose is measured in the presence of bovine plasma. The RMSEP is 83.16 mg/dL (4.62 mM) with 85% of the validation points falling within the A and B range of the Clarke error grid. Finally, to evaluate the real-time response of the sensor, the 1/e time constant for glucose partitioning and departitioning in the bovine plasma environment was calculated. The time constant is 28 s for partitioning and 25 s for departitioning, indicating the rapid interaction between the SAM and glucose that is essential for continuous sensing.

Animals↗

Glucose sensing using near-infrared surface-enhanced Raman spectroscopy: gold surfaces, 10-day stability, and improved accuracy.

This research presents the achievement of significant milestones toward the development of a minimally invasive, continuously monitoring, glucose-sensing platform based on the optical quantitation of glucose in interstitial fluid. We expand our initial successes in the measurement of glucose by surface-enhanced Raman scattering (SERS), demonstrating substantial improvements not only in the quality and optical properties of the substrate system itself but also in the robustness of the measurement methodology and the amenability of the technique to compact, diode laser-based instrumentation. Herein, we compare the long-term stability of gold to silver film over nanosphere (AuFON, AgFON) substrates functionalized with a partitioning self-assembled monolayer (SAM) using both electrochemical and SERS measurements. AuFONs were found to be stable for a period of at least 11 days. The switch to AuFONs not only provides a more stable surface for SAM formation but also yields better chemometric results, with improved calibration and validation over a range of 0.5-44 mM (10-800 mg/dL). Measured values for glucose concentrations in phosphate-buffered saline (pH approximately 7.4) based on 160 independent SERS measurements on AuFONs have a root-mean-square error of prediction of 2.7 mM (49.5 mg/dL), with 91% of the values falling within an extended A-B range on an expanded Clarke error grid. Furthermore, AuFONs exhibit surface plasmon resonances at longer wavelengths than similar AgFONs, which make them more efficient for SERS at near-infrared wavelengths, enabling the use of low-power diode lasers in future devices.

Glucose↗

Exact solution of Maxwell's equations for optical interactions with a macroscopic random medium: addendum.

This Addendum provides a revised set of figures containing converged numerical data for total scattering cross section (TSCS), replacing the figures in our recent publication [Opt. Lett. 29, 1393 (2004)]. Due to the use of an overly large time step, our original TSCS data exhibited a systematic, nonphysical diminution above 150 THz for all cases studied. We have determined that numerical convergence in the temporal sense for the pseudospectral time-domain (PSTD) algorithm employed previously requires limiting the time step to no more than 1/60th of the sinusoidal period at the maximum frequency of interest, which in the previous case was 300 THz. This is an important point that we hereby report to future users of PSTD simulations in electrodynamics and optics. Note that all our original conclusions remain valid.

Algorithms↗

Stokes polarimetry imaging of rat-tail tissue in a turbid medium using incident circularly polarized light.

BACKGROUND AND OBJECTIVES: We describe a Stokes polarimetry imaging technique that quantifies the polarization properties of remitted light backscattered from a sample. STUDY DESIGN/MATERIALS AND METHODS: Right- and left-circularly polarized near-infrared light was used to illuminate rat-tail tissue embedded in turbid gelatin. RESULTS: The degree of linear polarization (DoLP) and degree of circular polarization (DoCP) image-maps indicate that increasing the depth of the rat tail within the turbid medium and varying the rat-tail geometry and orientation relative to the light source affected the contrast between structures and adjacent tissue layers. CONCLUSION: Stokes polarimetry imaging shows that the intervertebral discs and soft tissue regions of rat tails strongly depolarize incident circularly polarized light. Tendon regions remit light with a more linear form due to birefringence. Both DoLP and DoCP image-maps provide contrast between tissue structures. When differentiating between unpolarized light and light with low DoCP or DoLP, the polarization of backscattered light from the turbid medium must to be taken into consideration.

Algorithms↗

Light-induced modulation of Porphyromonas gingivalis growth.

The bacterium Porphyromonas gingivalis is a clinically significant agent in periodontitis, a disease for which there is no definitive cure. Several groups have attempted to kill this bacterium using low levels of light in the absence of a photosensitizer, with conflicting results. We hypothesize that it is not possible to kill P. gingivalis by targeting endogenous porphyrins for a photochemical reaction. We demonstrated that irradiation of P. gingivalis with 455 or 625 nm light emitting diodes did not induce a photochemical killing of the cultures. Controlled temperature experiments indicate that irradiation at either wavelength did not significantly impact the growth of P. gingivalis cultures, as compared to non-irradiated controls. Rather, the irradiation caused a temperature increase in the growth medium, which altered the growth of the cultures. These results indicate that heat-induced killing of P. gingivalis could be the mechanism behind successful irradiation experiments with this bacterium.

Light↗

Exact solution of Maxwell's equations for optical interactions with a macroscopic random medium.

We report what we believe to be the first rigorous numerical solution of the two-dimensional Maxwell equations for optical propagation within, and scattering by, a random medium of macroscopic dimensions. Our solution is based on the pseudospectral time-domain technique, which provides essentially exact results for electromagnetic field spatial modes sampled at the Nyquist rate or better. The results point toward the emerging feasibility of direct, exact Maxwell equations modeling of light propagation through many millimeters of biological tissues. More generally, our results have a wider implication: Namely, the study of electromagnetic wave propagation within random media is moving toward exact rather than approximate solutions of Maxwell's equations.

Computer Simulation↗

Variation of corneal refractive index with hydration.

We report the effect of changes in the corneal hydration on the refractive index of the cornea. Using optical coherence tomography (OCT), the geometrical thickness and the group refractive index of the bovine cornea were derived simultaneously as the corneal hydration was varied. The corneal hydration was then calculated from the corneal thickness. The group refractive index of the cornea increased non-linearly as the cornea dehydrated. In addition, a simple mathematical model was developed, based on the assumption that changes in corneal hydration occur only in the interfibrilar space with constant water content within the collagen fibrils. Good agreement between the experimental results and the mathematical model supports the assumption. The results also demonstrate that the measurement of refractive index is a quantitative indicator of corneal hydration.

Animals↗

A glucose biosensor based on surface-enhanced Raman scattering: improved partition layer, temporal stability, reversibility, and resistance to serum protein interference.

This work updates the recent progress made toward fabricating a real-time, quantitative, and biocompatible glucose sensor based on surface-enhanced Raman scattering (SERS). The sensor design relies on an alkanethiolate tri(ethylene glycol) monolayer that acts as a partition layer, preconcentrating glucose near a SERS-active surface. Chemometric analysis of the captured SERS spectra demonstrates that glucose is quantitatively detected in the physiological concentration range (0-450 mg/dL, 0-25 mM). In fact, 94% of the predicted glucose concentrations fall within regions A and B of the Clarke error grid, making acceptable predictions in a clinically relevant range. The data presented herein also demonstrate that the glucose sensor provides stable SERS spectra for at least 3 days, making the SERS substrate a candidate for implantable sensing. Glucose sensor reversibility and reusability is evaluated as the sensor is alternately exposed to glucose and saline solutions; after each cycle, difference spectra reveal that the partitioning process is largely reversible. Finally, the SERS glucose sensor successfully partitions glucose even when challenged with bovine serum albumin, a serum protein mimic.

Animals↗

Phase-slope and group-dispersion calculations in the frequency domain by simple optical low-coherence reflectometry.

We report a new method by which phase slope and group dispersion can be calculated with a simple optical low-coherence reflectometer to quantify physiological conditions. A discrete-time signal processing algorithm based on the first and second derivatives of the phase with respect to wave number was developed from discrete-time Fourier properties. The algorithm avoids the 2pi ambiguity associated with most phase unwrapping. Experimental data collected by use of well-characterized optical materials validated the algorithm, which was minimally sensitive to phase noise. The group dispersion of bovine cornea was measured at various hydrations and was significantly dependent on hydration. The results suggest that group dispersion is an indicator of corneal alterations.

Algorithms↗

Histologic analysis of the effect on dental pulp of a 9.6-microm CO(2) laser.

BACKGROUND AND OBJECTIVE: Both patients and dentists would like a replacement of the dental drill. During the last decade, lasers have been investigated as a possible replacement. For lasers to be accepted, studies must show that their effect on the dental pulpal tissues is equal to or less noxious than those effects caused by the dental handpiece (drill). STUDY DESIGN/MATERIALS AND METHODS: In this study, two laser systems were used; the first was a breadboard CO(2) laser and the second a prototype clinical CO(2) laser system both emitted 60-micros-long pulses of 9.6-microm radiation. On the delivery system of both lasers, a scanner moved the focussed beam in a circular pattern and a water spray system served to cool the ablation site. Both lasers were used to create holes of similar dimensions in canine teeth. The treated teeth were then restored and harvested at either 4 days or 4 weeks. The teeth were decalcified, sectioned, and stained for examination via light microscopy. RESULTS: The histologic examination revealed normal pulpal tissues in the canine teeth treated with both CO(2) lasers. Some histologic sections showed an increase in the predentin layer, 28 days after laser treatment. While many histologic sections showed normal pulpal architecture following handpiece treatment, some sections showed total disruption of the normal pulpal histology. CONCLUSIONS: Histologic evaluation revealed that the lasers produced no noticeable damage to the dental pulpal tissue and appear to be a safe method for removing dental hard tissues. From this study, it appears that 9.6 microm CO(2) laser does not cause damage to the dental pulpal tissues in dogs.

Animals↗

Comparative study of polarized light propagation in biologic tissues.

We report the depolarization of light scattered by a variety of birefringent and nonbirefringent tissues. We used Stokes polarimetry to investigate how scatterer structures in each tissue contribute to the depolarization of linearly versus circularly polarized light propagating through that tissue. Experiments were performed on porcine blood, fat, tendon, artery, and myocardium. The results indicate that the two incident polarization states are depolarized differently depending on the structure of the sample. As seen in sphere suspensions, for tissues containing dilute Mie scatterers, circularly polarized light is maintained preferentially over linearly polarized light. For more dense tissues, however, the reverse is true. The results illustrate situations where polarized light will provide an improvement over unpolarized light imaging, information that is crucial to optimizing existing polarimetric imaging techniques.

Animals↗

Stokes polarimetry imaging of rat tail tissue in a turbid medium: degree of linear polarization image maps using incident linearly polarized light.

Illumination with incident linearly polarized light on tissue and polarization state measurements of the remitted light provide a means by which various tissue structures can be differentiated. A rat tail is embedded within a turbid gelatin such that there is a variable depth of medium above it. By varying the incident polarization angle (IPA) of the illuminating linearly polarized light, the geometry, and the orientation angle of the tissue, a series of 2-D degree of linear polarization image maps are created using our Stokes polarimetry imaging technique. The image maps show locations of the polarization-sensitive structures in the rat tail, including soft tissue, intervertebral disks, and tendons. The observed morphologies in the image maps indicate locations where the depolarization of light differs according to the tissue type and underlying layers. The data indicate the importance of varying the IPA, and that tissue dichroism and birefringence affect the degree of linear polarization image maps. Diagnostic information regarding subsurface tissue structures is obtained.

Animals↗