This PDF file contains the front matter associated with SPIE Proceedings Volume 12840, including the Title Page, Copyright information, Table of Contents, and Conference Committee information.

The time instability of regular biological tissue makes repeatable optical tomography imaging experiments through tissue difficult, hence the need for long life tissue phantoms with adjustable scattering parameters. Our test phantoms employ a wide density range of intralipid-infused agar layers 1-6 mm thick building phantoms with small to large scattering parameters of values μs =< 20cm^-1, g = 0.95. The intralipid-infused agar is encapsulated within clear polymer stabilizing these for >10 years creating samples with ranges of thicknesses, scattering characteristics and shapes. To tune phantoms we have created an improved rapid measurement method for scattering coefficients μs and anisotropy factor g. Using a DSLR camera with full frame 36x24mm sensor we 3D printed an optical jig which mounts phantoms like a lens to the camera. Aligning laser beams to the phantom a single picture captures ~6 million pixel values over +/-12°, creating 20,000 measurements each at 2300 angular bins of 0.005°. Matlab programs calculate the scattering center and concentric circles of pixels at each angular position. Nonlinear curve fitting the two term Henyey-Greenstein model extracts the pairs of HG parameters: weighing factors, μs and g parameters. Fits are highly statistical significance with exceedingly small deviation from the HG model. Each of 3 test phantom were measured a wide wavelengths range: 405, 532, 632, 670 and NIR 808 nm. The heat mirrors in regular DSLR/Mirror cameras still allow NIR measurements (to ~1000 nm) due to the very low noise of these photography systems.

This paper presents a novel approach for pathogenic bacteria detection (PathoBactD) through the utilization of a surface plasmon resonance (SPR)-based biosensor. The sensor consists of a BK7 prism coated with silver (Ag), barium titanate (BaTiO₃), and molybdenum diselenide (MoSe₂) in the Kretschmann arrangement. The proposed SPR-based biological sensor incorporates the concept of attenuated total reflection (ATR) for accurate measurements. Various performance characteristics of the sensor, including sensitivity, figure of merit (FoM), signal-to-noise ratio (SNR), detection accuracy, and quality factor, have been thoroughly analyzed. The integration of BaTiO₃ significantly enhances the sensor's capability for PathoBactD. To evaluate the impact of the BaTiO₃ layer on the performance parameters of the MoSe₂-based SPR biological sensor, a theoretical model employing the angular interrogation technique has been developed.

Definite diagnosis of brain neoplasms has been a challenge of neurosurgery practice especially when open surgery is not feasible to obtain adequate tissue samples for pathological investigation (e.g., for deep-seated tumors or tumors of eloquent areas undergoing biopsies or recurrent cases in patients that are candidates for palliative care). This complexity is exacerbated due to tumor heterogeneity, particularly when relying on limited samples obtained through stereotactic biopsies, which increases the risk of misdiagnosis. Addressing this critical issue, we propose a novel, label-free diagnostic approach by combining the strengths of polarimetry and speckle pattern analysis. This research introduces an innovative method that integrates Mueller matrix polarimetry with dynamic laser speckle analysis, offering a promising avenue for precise differentiation of biomedical samples and tissues. We validate the effectiveness of our technique by calculating the Mueller matrix images of the two various subtypes of brain neoplasms, followed by speckle pattern analysis through both numerical and graphical statistical post-processing. The results indicate considerable discrimination between the tissues, highlighting the potential of this methodology as an easily implementable non-invasive quantitative tool for analyzing extensive cancerous specimens.

The COVID-19 pandemic is a once-in-a-lifetime public health threat. The pandemic has had a significant impact on both individuals and communities’ health, safety, and well-being. Because COVID-19 is an extremely infectious and has nonspecific symptoms that are easily confused with the typical flu, it is critical to have precise diagnostic techniques readily available. There is an urgent need for quick detection of the SARS-CoV-2 virus due to the COVID-19 pandemic. Here, we present highly sensitive gold nanoparticle-enhanced localized surface plasmon resonance (LSPR) technique for detection of SARS-CoV-2 virus. Surface plasmon resonance is a powerful method for getting label-free, real-time information about the interaction of two binding partners. Gold nanoparticles (AuNPs) were used as signal enhancers in the diagnosis of SARS-CoV- 2 virus using the LSPR technique. Gold nanoparticles are stable against oxidation, great biocompatible, non-cytotoxic and have unique optical characteristics. These specific properties make AuNPs the most potential nanomaterial for different applications such as ultrasensitive detection and biological sensing.

Optimal bone surface preparation is essential for successful implant fixation and alignment in joint replacement procedures. Conventional knee arthroplasty prepares the bone surface for an implant with a series of flat cuts, not because of medical necessity but due to the constraints of the cutting tool. These cuts are often inaccurate, and the constraint of flat cutting leads to significant bone removal and ligament sacrifice avoidable with a different cutting modality. Laser ablation presents an alternative to mechanical cutting tools. Laser bone ablation for crafting fine channels has been described, however its potential for 3D bone shaping has been hitherto unexplored. This study examines the feasibility of laser ablation, supported by real-time bone surface sensing, as an efficient tool for 3D bone shaping. The accuracy and efficiency of targeted laser bone ablation was assessed on four ex-vivo human distal femur specimens, aiming to shape the bone surface to match a target tessellated pyramid geometry. A pulsed Er:YAG laser, guided by a digital plan, meticulously sculpted the bone, achieving a mean removal rate of 0.151 ± 0.015 cm³/min without any signs of carbonization. The process showcased remarkable surface accuracy of 0.28 ± 0.24 mm, demonstrating its promise as a superior method for bone surface preparation, potentially advancing implant design and surgical techniques.

Chemotherapy is one of the most widely used cancer treatment modalities. However, its therapeutic outcome is not always sufficient due to the inefficient delivery of the administered anticancer drug to the tumors. To overcome this problem, a drug delivery system (DDS) that enables highly efficient delivery of a drug to a tumor must be developed. We previously developed a DDS based on nanosecond pulsed laser-induced photomechanical waves (PMWs), which can transiently enhance vascular permeability and hence drug accumulation in the tissue. On the other hand, some previous studies showed that PMWs themselves had the effects to kill tumor cells in vitro. In the present study, we first applied PMWs alone to subcutaneous tumors in mice and evaluated the cytocidal effect. We then applied PMWs to the tumors in combination with administration of an anticancer drug, cisplatin (CDDP), and evaluated enhancement of the antitumor efficacy. After seven days, the relative tumor volumes treated with PMWs alone were considerably smaller than those of untreated tumors, suggesting a photomechanical tumoricidal effect. Meanwhile, the tumor volumes treated with PMWs in combination with CDDP administration were significantly smaller than those of untreated tumors, indicating enhanced antitumor efficacy due to the synergistic effects of the photomechanical tumor inactivation and increased extravasation of CDDP by PMWs.

Breast cancer is the world's most prevalent cancer, with roughly 1 in 16 Americans being diagnosed within their lifetime. One form of treatment for breast cancer is hyperthermal therapy, which involves heating cancer tumors to between 43-50 °C to cause apoptosis and above 50 °C for necrosis. Lasers are an effective method to raise the temperature of tumors for apoptosis and necrosis. However, to date, no study has compared the efficiency of visible, near infrared and mid infrared lasers for hyperthermal treatments. Here, we present a finite element model simulation using COMSOL Multiphysics to compare hyperthermal therapy using 500 nm, 900 nm, 3 μm and 10 μm laser sources using a fiber optic delivery system. Our results indicate that mid-infrared lasers result in shorter treatment times, while near infrared wavelengths likely result in less healthy tissue damage.

Tuberculosis (TB) is a major global health issue. To address this, there is a need for rapid and highly sensitive diagnostic methods. Surface plasmon resonance (SPR) is a promising optical sensing platform for various medical applications due to its high sensitivity and label-free detection. In this study, we introduce and evaluate surface plasmon resonance phase difference (SPR-PD) as a novel approach for TB detection. Our method uses the optical properties of SPR-PD to monitor the interaction between MPT64 biomarkers and immobilized MPT64 antibodies on a sensor surface. MPT64 antibodies were immobilized on a gold-coated biosensor chip and the MPT64 TB antigen was added to the biosensing surface. To enhance the detection signal for biomolecular binding events, gold nanoparticles (AuNPs) were conjugated to the MPT64 secondary antibodies. Ultraviolet-visible (UV-vis) spectroscopy was used to characterize the conjugation. The optimized biosensor chip was then analyzed using the custom-built SPR-PD system. Our preliminary results demonstrate successful immobilization of MPT64 antibodies on the biosensing surface, facilitating the capture of MPT64 TB antigen. Furthermore, SPR-PD provides real-time insights into the binding events and enables the sensitive and specific detection of MPT64 TB antigen. Our findings highlight the successful detection of TB biomarkers.

In genetic research, detecting mutations in the genome is very important. In cancer research, identifying mutations that are responsible for the development of the disease is vital for managing the progression and spread of the disease. Identifying subtle mutations in sequences is difficult, and more sensitive methods are required. To this end, different techniques have been developed to detect these mutations. The increasing number of techniques suggests that a perfect technique is yet to be identified. Localized surface plasmon resonance (LSPR) biosensor is an efficient alternative technique for detecting mutations due to its highly confined and enhanced electric fields near an interface with rapid evanescent decay. LSPR does not need to be equipped with additional optical coupling devices, such as prisms or angular detectors. Further, its strong scattering coefficients and absorption capabilities eliminate the need for polarization restrictions. The low field decay length of 10-30 nm and the low sensitivity to bulk RI changes and stability to temperature fluctuations allow it to accurately track analytes close to their surfaces, and consequently detect small biological interactions. In this study, LSPR was able to detect and differentiate interactions between 100% complementary DNA sequences and uncomplimentary DNA sequences. Oligonucleotide probes immobilized on a gold-coated sensor slide were used as a source of DNA sequence, and the acquired results indicated that LSPR was successfully able to recognize changes between samples of 100% DNA hybridization and those with uncomplimentary sequences. Based on these results, LSPR can be used as a potential technique in the detection of viral mutation at a faster rate.

Tuberculosis (TB) remains one of the most important infectious diseases globally, killing approximately 1.5 million people annually. The burden of infection is disproportionately high in low-income and resource-limited settings. This disparity is exacerbated by the emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis (Mtb), the bacterium that causes TB. Early detection and treatment of TB remain key strategies to reduce the spread and disease progression to drug-resistant forms of TB. However, this is hampered by slow, insensitive diagnostic methods, particularly for the detection of drug-resistant forms and in patients with human immunodeficiency virus infection (HIV). There are currently several rapid TB diagnostics, but most are limited due to costs and accessibility. Several genes, such as catalase-peroxidase (katG) and enoyl reductase (inhA) genes, contain mutations that are responsible for drug resistance. One of the initial objectives of this study was to use an optical-based system to detect katG and inhA genes. Deoxyribonucleic acid (DNA) probes, specific for katG and inhA, were used as biorecognition elements to capture katG and inhA target DNA. The katG and inhA gene-specific DNA probes were immobilized on a coated glass substrate before the target DNA was introduced for detection. As a negative control, a mismatched probe, unspecific to both genes was used for confirmation of the absence of the two genes in the experimental setup. The optical setup was used for the analysis of the binding interactions occurring on the coated glass substrate. The specificity and sensitivity of the coated glass substrate successfully detected the binding interactions through the changes in the transmitted intensity. The transmitted intensity further indicated the kinetics associated with DNA hybridization occurring between the target DNA and the capture probe. This is the initial step to potentially detecting drug-resistant mutations using optical-based biosensors at a point-of-care setting.

Surface plasmon resonance (SPR) is an optical phenomenon used for detecting various biological substances and disease diagnostics due to its high sensitivity. SPR-based biosensors are highly sensitive optical devices and rapid detection devices, and they also have the added advantage of being label-free biosensors. Sensitivity and limit of detection are critical parameters in studying the performance of any biosensor. In plasmonic biosensors, the sensitivity and limit of detection are dependent on several parameters and a sensitivity analysis is critical to determine these parameters which can optimize our biosensor performance. Sensitivity analyses of SPR-based biosensors are important for enhancing the limit of detection (LoD), comparing performance, optimizing biosensor design, ensuring quality control, and advancing biosensing technology. In this study, we theoretically perform a sensitivity analysis on an SPR-based biosensor and consider different ways to enhance the LoD of the biosensor. The interaction we study is that of different proteins binding to gold (Au) surfaces via an electrostatic mechanism. In this study, we vary a wide range of parameters ranging from metal film thickness, and wavelengths of light incident on the biosensor and show how these parameters can be used to optimize our plasmonic biosensor in terms of sensitivity and LoD. The development of optimal biosensors is ever more critical, particularly considering recurring pandemics and disease outbreaks. Good sensitivity analysis can lead to high quality and highly effective biosensors which can be useful in the fight against disease outbreaks and pandemics.

In the measurement of tissues using Fourier-domain optical coherence tomography (FD-OCT), speckle patterns from dynamic and static components often exhibit distinct characteristics: the former can be reduced through incoherent averaging, while the latter cannot. However, in the conventional Monte Carlo (MC) based simulations of FD-OCT, the speckle patterns of dynamic medium and static regions cannot be distinguished due to the random spatial distribution of scattering events across the entire simulated phantom. To tackle this issue, we propose a hybrid phantom model for MC-based realistic simulation of speckles in FD-OCT. In the simulation using the proposed model, static tissue within the 3D structure is modeled as a swarm of fixed particles loosely packed in the background medium. Once a photon is emitted into the static tissue model, it keeps moving until encountering a fixed particle and undergoing scattering. On the other hand, the spatial distribution of scattering points in the dynamic medium is still assumed random, which makes the photon’s step size sampled based on the wavelength-dependent scattering coefficient. Compared to conventional MC simulations, speckles simulated with the proposed model at different time points exhibit a higher spatial correlation in the static structures, which allows them to remain after incoherent averaging. In contrast, speckles in the dynamic component manifest de-correlation across multiple simulations. Future works involve leveraging this method to simulate dynamic OCT and linking structural information with speckle patterns to solve inverse problems.

Photobiomodulation therapy is successfully applied in several medical fields, despite the fact that mechanisms underlying photobiomodulation are not yet fully clear. Cell cultures are one of the most exploited tools to study the processes that regulate photobiomodulation, even if they have some limitation. One of the main problem arising when studying the interaction of light with cell culture, is the interaction between the electromagnetic radiation and the cell culture medium. This interaction can limit the feasibility and reliability of the experimental results. In previous studies conducted on different cell types isolated from skin tissue, we have shown that low doses of blue LED light interact with cells, increasing the outward currents, viability, and proliferation, but without increasing the reactive oxygen species and damaging the mitochondria. These studies were performed following different experimental protocols, irradiating the cells both in the culture medium and without the medium. In order to further clarify our findings, we are now exploring the possible interactions between the medium for cell cultures (Dulbecco Modified Eagle’s Medium (DMEM)) and the electromagnetic radiation, irradiating medium samples with different doses of blue LED light (410-430 nm). The directly irradiated samples were then analyzed with Near-Infrared and Raman spectroscopy. Our results point out that the irradiated DMEM shows a a different spectral beahviour at high fluences (>40 J/cm2); moreover, these modifications are correlated to the riboflavin component currently used in the medium.

Laser lithotripsy, employing long-pulsed lasers, creates channels for energy delivery to stones via cavitation bubbles. This study explored the effect of laser power density at water entry on energy transfer efficiency. Utilizing a 2.94 μm pulsed laser, it was found that decreasing the laser spot size at the water entry point significantly enhances the energy directed to the stone, while keeping the energy output and beam divergence constant. Furthermore, the technique of inserting a sapphire glass at a 45° angle to the laser path provided a novel means to observe the internal structures of the cavitation bubbles, potentially refining the control and efficacy of the lithotripsy process.

Plasmonic biosensing is an area of research where scientists are developing novel devices and concepts. The validation of these devices requires thorough testing of key characteristics, including accuracy, specificity, robustness, and linearity, all of which are interconnected with a system's limit of detection. By optimizing parameters to meet these criteria, the development of highly sensitive and specific biosensing devices can be facilitated, allowing for effective performance comparisons with other biosensing devices. The limit of detection is a measure of the ability to detect small traces of molecules in each solution, and it can be used to measure the performance of a biosensing system. In this study, we evaluated the limit of detection of a home-built localized surface plasmon resonance (LSPR) system. To this end, gold-coated and titanium-coated slides were exposed to neutravidin and biotinylated probes at varying concentrations ranging from 100 μM to 6.125 μM, without the presence of an analyte. By analyzing the transmitted intensity against concentration, we constructed a reliable sensing curve. Through linear regression analysis, we determined the slope of the linear calibration function with high precision. By evaluating the limit of detection, this study will contribute to the understanding of the performance capabilities of the localized surface plasmon resonance technique. The findings presented here serve as a valuable benchmark for developing and comparing highly sensitive and specific biosensing devices.

Tuberculosis (TB) is one of the most prevalent infectious diseases globally. Although it is curable, several factors, such as the inappropriate use of treatment drugs lead to drug-resistant strains of TB. The burden of infection is disproportionately high in low-income and resource-limited settings. Furthermore, this disparity is exacerbated in patients with already compromised immune systems. Therefore, early detection and treatment of TB play an important role in reducing the spread and progression to drug-resistant disease forms. There are currently a few rapid multi-drug resistant TB diagnostic tests available, however, most are limited due to costs and accessibility. Several genes, such as catalase-peroxidase (katG) and enoyl reductase (inhA) genes, contain mutations that are responsible for resistance to the TB drug, isoniazid. We therefore, aim to use a custom-built surface plasmon resonance (SPR) system to detect katG and inhA genes. Deoxyribonucleic acid (DNA) probes, specific for katG and inhA, were used as biorecognition elements to capture katG and inhA target DNA. The katG and inhA gene-specific DNA probes were immobilized on a gold-coated glass sensor chip before the target DNA was introduced for detection. As a negative control, a mismatched probe, unspecific to both genes was used for confirmation of the absence of the two genes in the experimental setup. The specificity and sensitivity of the capture probes to the target DNA were investigated using the gold-coated glass sensor chip on the SPR setup. The changes in the resonance angle dip indicated the hybridization of the target DNA and the capture probe. The results from this study will contribute to the optimization of an optical-based biosensor detecting drug-resistant mutations.

Human immunodeficiency virus type 1 (HIV-1) is the causative agent of acquired immunodeficiency syndrome (AIDS), a severe infectious disease that has resulted in millions of deaths worldwide. Timely and accurate diagnosis of HIV-1 is crucial in reducing mortality rates associated with AIDS. In this study, we propose a real-time detection method for HIV-1 using an absorbance technique. Specifically, we compare the absorbance properties of three different biosensor surfaces: one coated with 10 nm titanium (Ti) the other coated with 50 nm gold (Au), and the other consisting of an uncoated glass slide. The gold-coated slide is preferred over the silver-coated slide because gold metal is considerably stable under testing conditions. In a quest to detect HIV-1, the glass, gold-coated and titanium-coated slides were successfully functionalized with relevant silanes (GMBS/3MPTS). To study the absorbance kinetics of the optical biosensor, we employ low-power light. As HIV-1 binds to the antibody on the surface, the binding interaction influences the absorbance of light as the sample passes through the functionalized surface. By monitoring the absorbance, we can deduce the capabilities of either Au, Ti, or Glass to detect the HIV-1 virus. By conducting this research, we aim to evaluate the efficacy of the Ti and Au-coated biosensor surface and consequently compare it to the uncoated glass slide on performance in detecting HIV-1 virus. The results provide insights into the performance of the biosensor with a specific metal for HIV-1 detection. This study contributes to the development of improved diagnostic tools for early HIV-1 diagnosis, ultimately aiding in the reduction of mortality rates associated with AIDS.

Tuberculosis (TB) remains a significant global health concern, necessitating the development of sensitive and efficient diagnostic methods. This study compares the performance of the custom-built Surface Plasmon Resonance (SPR) phase difference with conventional SPR in detecting the tuberculosis antigen MPT64. Our objective is to evaluate whether the SPR phase shift offers improved sensitivity compared to the conventional SPR technique. MPT64 antigen samples with varying concentrations were prepared and passed over the sensor chip. The resulting binding events were monitored using SPR phase difference and conventional SPR measurement techniques. Our findings demonstrate that SPR phase difference exhibits enhanced sensitivity compared to conventional SPR in the detection of MPT64 antigen. The SPR phase shift technique effectively amplifies the signal response and offers a greater dynamic range, enabling the detection of lower antigen concentrations. The experimental results were analyzed statistically, comparing the limits of detection between SPR phase difference and conventional SPR. The data indicate that the SPR phase difference outperforms the conventional SPR method in terms of sensitivity, highlighting its potential as a superior tool for TB antigen detection. The results obtained in this study may contribute to the advancement of TB diagnosis. The improved sensitivity offered by the SPR phase difference technique has promising implications for early and accurate TB diagnosis, aiding in the timely initiation of treatment and reducing disease transmission.

This work deals with the extent of damage to the skin surface when electromagnetic radiation with a wavelength λ = 10.6 μm is applied. This investigation aims to determine a threshold value above which skin damage occurs. For this purpose, a semi-automated evaluation routine was developed, tested and assessed. Skin damage was generated by applying a carbon dioxide laser in a line scan profile to pig skin which was selected to model human skin. Both, the laser power and the exposure time of the radiation were systematically varied. The samples were evaluated by VIS images on which a semi-automated evaluation routine was performed. The damage classification was based on the visible change of the thermally damaged zone. To reduce influences of the test personnel, a region of interest was defined in the center of each damage. The length was kept constant to ensure comparability. Based on the calculated data, the relation of the induced surface energy and the damaged area could be displayed and analyzed. The progression follows a sigmoidal function, so that above a threshold value a sharp increase in damage can be observed in the exposed area.

Chitosan-based nanoparticles (NPs) are well-known for their safely, nontoxicity, biocompatibility, and biodegradability. Since highly infectious viral diseases such as Covid-19 spread quickly, it is important to be able to diagnose these diseases early to prevent the infection from spreading. In this study, we developed a novel highly sensitive chitosan/gold nanoparticles based LSPR sensor for SARS-CoV-2 virus detection. Localized surface plasmon resonance (LSPR) is an optical phenomenon caused by collective electron charge oscillations in metallic nanoparticles excited by light source. The nanocomposites of gold nanoparticles (AuNPs) with chitosan were synthesized by the reduction technique. Chitosan/Au nanocomposites were synthesized by reducing gold salt using chitosan. Chitosan acted as a reducing/stabilizing agent to produce composites. SARS-CoV- 2 antibodies were conjugated with Chitosan/Au nanocomposites for detection of the target antigen using LSPR.