This PDF file contains the front matter associated with SPIE Proceedings Volume 11626, including the Title Page, Copyright information, and Table of Contents.

COVID-19 pandemic has affected our lives in all aspects. Unfortunately, there is no reliable treatment or vaccine for SARS-CoV-2 right now. Photobiomodulation (PBM) is a photon therapy based on PBM which uses a light sourcing in the visible and near-infrared spectrum. It has general effects like metabolic, analgesic, anti-inflammatory and immunomodulatory effects. The most important method for COVID-19 management are oxygenation and faster rehabilitation of the damaged tissue, antiviral effects and finally controlling the cytokine storm by reducing inflammatory agents. Photobiomodulation may be used as an adjuvant therapy or even an alternative therapy for all these mechanisms without side effects and drug interactions. We can increase these effects by combining this method with another method known as antimicrobial photodynamic therapy, possibly. Antimicrobial photodynamic therapy (aPDT) has been investigated as a novel way of inhibiting bacterial, viral and fungal infections. Studies indicate that PBM and aPDT could be useful in many viral and bacterial pulmonary complications like Influenza, SARS-CoV, and MERS. In conclusion COVID-19 disease is very unknown, and scientists in any area must manage the challenge, in any way possible. According to mechanisms mentioned earlier, we are referring to the capabilities of photobiomodulation and photodynamic therapy. The best use is a combination of both methods. Present treatments are focused on virus removal, tissue oxygenation, and reduction of cytokine storm. In combination with these two methods, we can achieve these goals with minimal interference with pharmaceutical methods and battle this disease with biophysical agents.

The urgent need for antibody detection tools has proven particularly acute in the COVID-19 era. Array-based tools are desirable as methods for assessing broader patterns of antigen-specific responses, as well as for providing information on SARS-CoV-2 immunity in the context of pre-existing immunity to other viruses. To that end, this talk will describe the development of a label-free microarray for rapidly quantifying antibodies to SARS-CoV-2 and other upper respiratory pathogens. The approach is built on Arrayed Imaging Reflectometry (AIR), a label-free detection technique based on the creation and binding-induced degradation of an antireflective coating on the surface of a silicon chip. Performance of the array using a cohort of human samples (convalescent COVID-19 patients and negative controls) along with applications in screening monoclonal antibodies will be discussed.

As coronavirus disease 2019 (COVID-19) has spread across the world, the surge in patients requiring ICU admission has been overwhelming.The rapid diagnosis and isolation, clinical management, and infection prevention are the main challenges associated with this pandemic. When the disease becomes critical, adequate management of acute respiratory failure and supporting the hemodynamics is key in order to minimize the negative impact on survival. However, many questions on prognosis and efficient clinical management remain unanswered. HEMOCOVID-19 uses near-infrared diffuse optical technologies to non-invasively evaluate endothelial and microvascular dysfunction to aid both the development of targeted therapies and also to personalize rescue therapies. HEMOCOVID-19 has eleven partners in four countries and is open for new members. I will present the project and the preliminary results. I will then briefly explain the vision for the longer-term.

The SARS-CoV-2 pandemic has revealed the need for rapid and inexpensive diagnostic testing to enable population-based screening for active infection. Neither standard diagnostic testing, the detection and measurement of viral RNA (via polymerase chain reaction), or serological testing (via enzyme-linked immunosorbent assay) has the capability to definitively determine active infection. The former due to a lack of ability to distinguish between replicable and inert viral RNA, and the latter due to varying immune responses (ranging from latent to a complete lack of immune response altogether). Despite many companies producing rapid point-of-care (POC) tests, none will address the global scale of testing needed and few help to combat the ever growing issue of testing resource scarcity. Here we discuss our efforts towards the development of a highly manufacturable, microfluidic device that instantly indicates active viral infection status from ~ 20 μL of nasal mucus or phlegm and requires no external power. The device features a biotin functionalized silicon nanomembrane within an acrylic body containing channels and ports for sample introduction and analysis. Virus capture and target confirmation are done using affinity-based capture and size-based occlusion respectively. Modularity of the device is proven with bead and vaccinia virus capture as we work towards testing with both pure SARS-CoV-2 virus and human samples. With success on all fronts, we could achieve an inexpensive POC diagnostic which can determine an individual’s infection status, aiding containment efforts in the current and future pandemics. In addition to direct viral detection, our method can be used as a rapid POC sample preparation tool that limits the application of PCR reagents to those samples which already display viral size and antigen-based positivity through our device.

As a means of preventing airborne transmission of SARS-CoV-2, we advocate the immediate installation of the safe and proven upper room 254nm UVGI in indoor public spaces with low air changes per hour and/or recirculated air. We further believe that if the on-going research into the new 222nm UVGI continues to demonstrate its safety, then this technology should be adopted as it will work continuously to inactivate viruses and bacteria in the air we breathe and on surfaces we touch.

Photodynamic inactivation (PDI) has been widely applied to localized infections, both internal and external. However, there is a notable knowledge gap when it comes to applying PDI to an entire organ system or even systemically throughout an organism. To study these treatment methods, an in vivo murine model of MHV-1 is planned. As a respiratory coronavirus, the model provides a suitable system for study, in addition to potential determination of systemic results. Specifically applied, MHV-1 has many key characteristics, such as symptoms and viral protein structures, that are in common or similar to other coronaviruses. Thus, this theorized model simultaneously addresses a key knowledge gap and provides useful insights into potential treatments for COVID-19 and similar disease-causing viruses. The risk of emergent viral threats and the necessity for rapidly developed, adaptable, affordable treatment methods are both now vividly evident.

A flexible membrane based Surface-Enhanced Raman Spectroscopy (SERS) sensor was developed as a viable point-of-care platform to monitor changes of these surrogate indicators of healing status in chronic wounds, such as tumor necrosis factor alpha (TNFα) and matrix metalloproteinase (MMPs). In terms of performance, SERS approach is superior to enzyme-based assays, which are resource intensive. We demonstrated the efficiency of this flexible SERS platform for the sensitive detection of TNFα and MMP9 in the nM to pM range. These substrates may be incorporated into wound dressings to permit routine monitoring of wound status.

Supercritical angle fluorescence (SAF) is a surface sensitive detection mechanism that has been used to perform rapid, sensitive detection of biomolecules. However, the SAF biosensors that have been demonstrated so far have been either bulky and expensive or small and affordable while sacrificing on sensitivity . We present a novel interference based SAF biosensor technology that has the potential to be fast, small, inexpensive and mass manufacturable while being as sensitive as the current gold standard. This technology can therefore create biosensors in a wide range of form factors, from large, complex high multiplex devices to small handheld point of care solutions.

Gastrointestinal disorders such as colorectal cancer or inflammatory bowel disease are linked to gut dysbiosis, an unbalanced gut microbiota. This early manifestation of the disease alters colon epithelial metabolism influencing the gut autofluorescence emission, which is susceptible to carry diagnostic value. We analyzed the fluorescence properties of healthy and dysbiotic ex vivo murine colons with an intraluminal fiber-based fluorescence lifetime imaging (FLIm) instrument. The results indicate that fluorescence lifetime reacts to inflammation in a spectrally dependant manner, and the full-length colon images allow to localize specific areas of activity. Imaging results were correlated to biochemical metabolic readouts (i.e. intracellular NADH, lactate) to establish the diagnostic potential of intraluminal FLIm.

We demonstrate an automated, cost-effective system that delivers early antimicrobial-susceptibility-testing results, minimizing incubation time and eliminating human errors, while remaining compatible with standard clinical workflow. A neural network processes the time-lapse intensity information from a fiber-optic array to detect growth in each well of a 96-wellplate. Our blind testing on clinical Staphylococcus aureus infections reveals that 95.03% of all the wells containing growth were correctly identified, with an average incubation time of 5.72-h. This deep learning-based optical system met the FDA-defined essential and categorical agreement criteria for all 14 antibiotics tested, after an average of <7-h of incubation time.

A middle ear infection is a prevalent inflammatory disease during childhood, often caused by bacterial pathogens. A portable and replaceable microplasma jet array was developed to investigate the feasibility of inactivating Pseudomonas aeruginosa, a common bacterial strain associated with middle ear infections. Reactive species generated by the non-thermal microplasma jet array inactivated planktonic bacteria and biofilm. A middle ear phantom was developed using the rat eardrum to study the antimicrobial effects on bacteria located behind the eardrum. Lastly, 3D volumetric OCT imaging and histology were performed on the rat eardrum to examine the potential structural changes due to the plasma.

Despite advances in image-guided percutaneous drainage, deep tissue abscesses remain a serious cause of morbidity, mortality, and hospital stay. We initiated a Phase 1 clinical trial exploring safety and feasibility of methylene blue (MB) photodynamic therapy during drainage. Five subjects have been treated, with no study-related adverse events and high technical success. Monte Carlo simulations were used to examine effects of optical properties on delivered light dose. We found that light dose is highly dependent upon MB uptake and Intralipid concentration. These results motivated construction of an optical spectroscopy system for determination of abscess wall optical properties in vivo.

Pseudomonas (P.) aeruginosa is a typical Gram-negative bacterium to cause burn wound infection, which is hard to control since P. aeruginosa efficiently forms biofilms and easily acquires drug resistance, resulting in septicemia. Antimicrobial photodynamic therapy (aPDT) is a new approach for controlling such burn wound infection, and we showed a certain effectiveness of methylene blue (MB)-mediated aPDT with LED array illumination for a rat model with an extended, full-thickness burn infected with P. aeruginosa. However, rapid bacterial regrowth was observed even after consecutive daily aPDT, indicating efficient bacterial invasion into the tissue. Thus, it is crucial to evaluate the aPDT efficacy in a depthresolved manner. In this study, we analyzed depth distributions of bacteria for the rat treated with saline (control), rat treated with a photosensitizer mixture alone (PS alone) and rat treated with a PS mixture plus light (aPDT) based on Gramstained tissue sections for the same rat model as that described above. For the control rat, large number of bacteria were observed on the tissue surface and in the wide depth range of the skin. For the PS alone rat, many bacteria were observed on the tissue surface and in the epidermal region, but the number of bacteria was limited in the deeper region of the skin, indicating a PS mixture dark toxicity. The aPDT showed drastic decreases in the number of bacteria both on the tissue surface and in the subsurface region; however, there were still certain numbers of bacteria in the deeper region of the skin.

Bacteria-specific phototoxic reactions were triggered by blue light (BL) and edible carvacrol leading to safe and broad spectrum of bactericide, in sharp contrast to anti-microbial photodynamic therapy that has a relatively poor selection. While anti-microbial photodynamic therapy triggers the generation of cytotoxic reactive oxygen species (ROS) in both bacteria and mammalian cells, BL paired with carvacrol induced phototoxic reactions resulting in robust ROS generation only in bacteria, as demonstrated by UPLC-VION-IMS-QTOF-MS/MS analyses in vivo and in vitro. This highly selective phototoxic reaction represents a unique strategy to combat the growing threat of MDR bacteria

Antimicrobial resistance is a concern to public health, with methicillin resistant Staphylococcus aureus (MRSA) being particularly important. Blue light at 405 nm has demonstrated efficacy for the treatment of localized infections. With respect to MRSA, aBL is not effective enough to be developed into a stand-alone therapy. Findings demonstrated the antioxidant properties of the S. aureus pigment, staphyloxanthin (STX). We hypothesized that the efficacy of 405 nm light on MRSA may improve with STX photolysis using 460 nm light. We report an approach that exploits the STX photolysis effect of 460 nm light to sensitize MRSA to 405 nm light.

Fibromyalgia (FM) is a painful syndrome with a generalized and chronic characteristic in the musculoskeletal system, but not articular. It is present on average from 2 to 5% of the world population. It is predominant in the female gender, with 10 individuals, from 7 to 9 being women, with a higher prevalence between 35 to 45 years of age ^1,2. The origin of the syndrome is still unknown and the diagnosis must be made clinically, as there are no laboratory and imaging tests for FM. In addition to the exacerbated painful aspect (hyperalgesia), other symptoms are associated, such as, intense fatigue, non-restorative sleep, mood disorders (anxiety and depression), cognitive changes (attention and memory), irritable bowel syndrome, paraesthesia, feeling of edema, among others, consequently, generates disabilities and leads to psychosomatic and psychosocial changes^3,4.

The use of diffuse reflection spectroscopy made it possible to determine the optical properties of the mucous membrane of the oral cavity of a pig. The binary diffusion coefficient of iodine in Lugol's composition (aqueous solution of iodine (0.01 w/w), potassium iodide (0.02 w/w) and glycerol (0.94 w/w)) was determined for the first time ex vivo in the lining of the alveolar gingiva pigs: (8.86±0.75)·10^–7 cm²/s. For the first time, the binary diffusion coefficient of glycerol was determined in the composition of Lugol (an aqueous solution of iodine (0.01 w/w), potassium iodide (0.02 w/w), and glycerol (0.94 w/w)) ex vivo in the lining of the alveolar gingiva pigs: (6.44±0.62)·10^-7 cm²/s. It was revealed that after complete staining of the gingiva with a dye, radiation does not pass into the biological tissue from 200-600 nm, which includes the areas of iodine absorption peaks, and starting from 650-800 nm, the effect of optical clearing is observed with an efficiency of up to 120%.

Early detection of prostate cancer is critical for the success of cancer therapy. It is believed that the biochemical changes that cause the optical spectra changes would appear earlier than the histological aberration. The aim of this ex vivo study was to evaluate the ability of Stokes Shift Spectra (S3) to identify human prostate cancerous tissues from the normal. Fifteen (15) pairs of with pathologically confirmed human prostate cancerous and normal tissues underwent Stokes Shift Spectra measurements with selective wavelength interval of 40 nm. The spectra were then analyzed using machine learning (ML) algorithms to classify the two types of tissues. The ML algorithms including principal component analysis (PCA) and nonnegative matrix factorization (NMF) were used for dimension reduction and feature detection. The characteristic component spectra were used to identify the key fluorophores related to carcinogenesis. The results show that these key fluorophores within tissue, e.g., tryptophan, collagen, and NADH, have different relative concentrations between cancerous and normal tissues. A multi-class classification was performed using support vector machines (SVMs). A leave-one- out cross validation was used to evaluate the performance of the classification with the gold standard histopathological results as the ground truth. The results with high sensitivity and specificity indicate that the S3 method is effective for detecting changes of fluorophore composition in human prostate tissues due to the development of cancer.

This study evaluated the feasibility of various 3D printed mid-turbinate swab designs in terms of both manufacturability and liquid retention. Earlier studies showed that mid-turbinate swab testing was a preferred SARS-CoV2 test method[1]. We chose to use HP Multi Jet Fusion (MJF) for manufacturing due to the need for rapid, cost-effective production. For each of the swab designs, we looked at their ability to hold fluid. The assumption was that the larger the test sample, the more likely the test would be accurate. We then looked at the manufacturing yield of each swab. After investigating each design configuration's liquid retention, quality, and production yield, we ranked these swabs based on three metrics: 3D print quality, post-print process quality, and sample collection efficiency. We found that our "wavy design" topped all three metrics.