Gerard Coté - Academia.edu (original) (raw)

Papers by Gerard Coté

Biomedical Optics Express, Jul 19, 2017

The quantification of visceral organ oxygenation after trauma-related systemic hypovolemia and sh... more The quantification of visceral organ oxygenation after trauma-related systemic hypovolemia and shock is critical to enable effective resuscitation. In this work, a photoplethysmography-based (PPG) sensor was specifically designed for probing the perfusion and oxygenation condition of intestinal tissue with the ultimate goal to monitor patients post trauma to guide resuscitation. Through Monte Carlo modeling, suitable optofluidic phantoms were determined, the wavelength and separation distance for the sensor was optimized, and sensor performance for the quantification of tissue perfusion and oxygenation was tested on the in-vitro phantom. In particular, the Monte Carlo simulated both a standard block three-layer model and a more realistic model including villi. Measurements were collected on the designed three layer optofluidic phantom and the results taken with the small form factor PPG device showed a marked improvement when using shorter visible wavelengths over the more conventional longer visible wavelengths. Overall, in this work a Monte Carlo model was developed, an optofluidic phantom was built, and a small form factor PPG sensor was developed and characterized using the phantom for perfusion and oxygenation over the visible wavelength range. The results show promise that this small form factor PPG sensor could be used as a future guide to shock-related resuscitation.

Microfluidics and Nanofluidics

Automated generation of a thin blood smear with a pumpless, capillary-driven, microfluidic would ... more Automated generation of a thin blood smear with a pumpless, capillary-driven, microfluidic would overcome the limitations of manually prepared smears and enable potential point-of-care (POC) applications. Herein, this was accomplished with microfluidic design that leveraged an amphiphilic silicone and channel pillars. The silicone (Sylgard 184) was combined with a surface-modifying additive (SMA), an amphiphilic poly(ethylene oxide) (PEO)-silane at varying concentrations (3, 5, and 7 wt%). The channels were formed with dimensions of 4.7 µm, 250 µm, and 16 mm (height × width × length, respectively). Pillar sections were added at the inlet, outlet and two interior sections to not only prevent channel collapse but to improve flow and cell distribution. After deposition of blood (0.3, 1, and 2 µL) to the channel inlet, the flow time and flow stop times were recorded and the channels imaged to assess smear uniformity and for automated cell counting. A thin blood smear was generated for microfluidic chips prepared with 5 wt% SMA and provided with 0.3 µL of blood.

The Analyst

A dual assay cartridge was developed and used in conjunction with a handheld reader for sensing %... more A dual assay cartridge was developed and used in conjunction with a handheld reader for sensing % glycated albumin to monitor gestational diabetes at home.

Journal of Biomedical Optics

Significance: Point-of-care (POC) platforms utilizing optical biosensing strategies can achieve o... more Significance: Point-of-care (POC) platforms utilizing optical biosensing strategies can achieve on-site detection of biomarkers to improve the quality of care for patients in low-resource settings. Aim: We aimed to develop a portable, multi-modal spectroscopic platform capable of performing Raman and fluorescence measurements from a single sample site. Approach: We designed the spectroscopic platform in OpticStudio using commercial optical components and built the system on a portable optical breadboard. Two excitation and collection arms were utilized to detect the two optical signals. The multi-modal functionality was validated using ratiometric Raman/fluorescence samples, and the potential utility was demonstrated using a model bioassay for cardiac troponin I. Results: The designed spectroscopic platform achieved a spectral resolution of 0.67 AE 0.2 nm across the Raman detection range (660 to 770 nm). The ratiometric Raman/fluorescence samples demonstrated no crosstalk between the two detector arms across a gradient of high molar concentrations. Testing of the model bioassay response showed that the integrated approach improved the linearity of the calibration curve from (R 2 ¼ 0.977) for the Raman only and (R 2 ¼ 0.972) for the fluorescence only to (R 2 ¼ 0.988) for the multi-modal approach. Conclusion: These findings demonstrate the potential impact of a multi-modal POC spectroscopic platform to improve the sensitivity and robustness necessary for biomarker detection.

Biosensors

Cardiovascular disease is the leading cause of death globally. To provide continuous monitoring o... more Cardiovascular disease is the leading cause of death globally. To provide continuous monitoring of blood pressure (BP), a parameter which has shown to improve health outcomes when monitored closely, many groups are trying to measure blood pressure via noninvasive photoplethysmography (PPG). However, the PPG waveform is subject to variation as a function of patient-specific and device factors and thus a platform to enable the evaluation of these factors on the PPG waveform and subsequent hemodynamic parameter prediction would enable device development. Here, we present a computational workflow that combines Monte Carlo modeling (MC), gaussian combination, and additive noise to create synthetic dataset of volar fingertip PPG waveforms representative of a diverse cohort. First, MC is used to determine PPG amplitude across age, skin tone, and device wavelength. Then, gaussian combination generates accurate PPG waveforms, and signal processing enables data filtration and feature extracti...

Analytical methods : advancing methods and applications, 2021

Effective staining of peripheral blood smears by increasing contrast of intracellular components ... more Effective staining of peripheral blood smears by increasing contrast of intracellular components and biomarkers is essential for the accurate characterization, diagnosis, and monitoring of various diseases such as malaria. To assess the potential for automation of stained whole human blood smears at the point-of-care (POC), brightfield and fluorescence staining protocols were adapted for smears generated in channels of pumpless microchannels and compared to a standard glass smear. A 3× concentration Giemsa brightfield staining solutions (10, 33, and 50% dilution), and Acridine Orange fluorescence staining solutions (12 μg mL-1) were evaluated with human blood smears containing malaria parasites within a microfluidic channel. Giemsa staining at 33% dilution showed an optimal combination of contrast and preservation of cellular morphology, while 50% dilutions showed significant cellular crenation and 10% dilutions did not show desired contrast in brightfield imaging. Fluorescence stai...

Nanoscale Advances, 2021

Here we report the synthesis of core–satellite nanoparticles to explore tunable SERS hot-spot gen... more Here we report the synthesis of core–satellite nanoparticles to explore tunable SERS hot-spot generation, signal reproducibility and long-term activity.

The Journal of Nutrition, 2001

With recent advancements in micro-fabrication and nano-fabrication techniques as well as advancem... more With recent advancements in micro-fabrication and nano-fabrication techniques as well as advancements in the photonics industry, there is now the potential to develop less invasive portable sensors for monitoring micronutrients and other substances used to assess overall health. There have been many technology innovations in the central laboratory for these substances for overall health status but the primary motivation for the research and development of a portable field instrument has come from a diabetic patient and market-driven desire to minimally invasively or noninvasively monitor glucose concentrations in vivo. Such a sensor system has the potential to significantly improve the quality of life for the estimated 16 million diabetics in this country by making routine glucose measurements less painful and more convenient. In addition, there is a critical need for the development of less invasive portable technologies to assess micronutrient status (iron, vitamin A, iodine and folate), environmental hazards (lead) and for other disease-related substances, such as billirubin for infant jaundice. Currently, over 100 small companies and universities are working to develop improved monitoring devices, primarily for glucose, and optical methods are a big part of these efforts. In this article many of these potentially less invasive and portable optical sensing technologies, which are currently under investigation, will be reviewed including optical absorption spectroscopy, polarimetry, Raman spectroscopy and fluorescence.

Biomedical Optical Spectroscopy and Diagnostics / Therapeutic Laser Applications, 1998

A system was developed using a Fourier Transform spectrometer configured for the near-infrared (2... more A system was developed using a Fourier Transform spectrometer configured for the near-infrared (2.0- 2.5 pm) range to investigate spectral differences between cancerous and normal oral tissue. Cancer was induced in the left or right cheek of hamsters. The animals were euthanized and cancerous as well as normal tissue was excised and analyzed in vitro. A total of 20 spectra were recorded 10 from cancerous tissue and 10 from normal tissue. Polynomial subtraction was used for preprocessing the raw spectral data. The preprocessed data were entered into a principal component analysis (PCA) algorithm which showed the ability to discriminate the tissue types across animals using this wavelength range.

... Valery V. Tuchin; Gregory E. Brill. New potentialities for noninvasive optical investigation ... more ... Valery V. Tuchin; Gregory E. Brill. New potentialities for noninvasive optical investigation of microcirculation in extended space missions. Author(s): Youri I. Gurfinkel; Valery M. Mikhailov. Computer simulation of the decay of nonlinear ...

Introduction to Biomedical Engineering, 2005

Publisher Summary This chapter provides students with a better understanding of the fundamental p... more Publisher Summary This chapter provides students with a better understanding of the fundamental principles associated with the growing field of biomedical optics as well as the design of optically based therapeutic, diagnostic, and monitoring devices. The chapter also describes the biochemical and biophysical interactions of optic and fiber optic systems with biological tissue and helps understand the photothermal interactions of laser systems with biological tissue. The propagation of light through biological media such as tissue begins with a simple ray optics approach for light traveling through a nonparticipating medium in which the effect of the absorption and scatter within the medium is ignored. The effects of absorption and scatter on light propagation have then been discussed along with the consideration of boundary conditions and various means of measuring the optical absorption and scattering properties.Several emerging imaging techniques are being developed by combining relatively transparent acoustic energy with strongly scattering light, which are called hybrid optical imaging. Ultrasound-modulated optical tomography, photoacoustic tomography, and sonoluminescence have been discussed.

Optics and Biophotonics in Low-Resource Settings V, 2019

Advances in consumer electronics and affordable high functioning optics have led to renewed inter... more Advances in consumer electronics and affordable high functioning optics have led to renewed interest in the development and application of portable microscopes for the remote diagnosis of diseases such as malaria. Indeed, better tools for malaria diagnosis are necessary to combat increasing rates of false-negative diagnosis and drug resistance. In this work, the capabilities and utility of a portable, multimodal microscopy system designed for malaria diagnosis are explored. The system, which combines off-the-shelf optical components with a Raspberry Pi for data collection and a microfluidic cartridge for sample preparation, is capable of capturing brightfield, fluorescent, and cross-polarized images of thin blood smears. Parameters for each imaging modality are defined and related to their potential diagnostic utility. Samples of Plasmodium falciparum cultures were stained either with fluorophores or with a dual Giemsa-fluorophore procedure and examined using the portable and gold-standard microscopes. Preliminary results indicate that the microscope is capable of nearly diffraction limited performance and can distinguish rings, trophozoites, and schizonts in fluorescence and brightfield modes along with hemozoin crystals in cross-polarized mode. Parasitemia measurements for simulated mixed-stage, severe infections show strong agreement with Giemsa-stained gold-standard measurements. If cost and durability limitations can be overcome, this microscopy system may be able to augment malaria-screening rapid diagnostic tests to enable the more precise distribution of antimalarial medications at the point-of-care.

Optical Diagnostics and Sensing XXI: Toward Point-of-Care Diagnostics, 2021

Gestational diabetes mellitus (GDM) affects between 2-14% of pregnant women in the United States ... more Gestational diabetes mellitus (GDM) affects between 2-14% of pregnant women in the United States every year. The glycated version of serum albumin, the most abundant protein in blood, owing to its half-life of ~21 days can effectively be used as an intermediate biomarker for monitoring GDM. Normal level of glycation of albumin is between 10-16% whereas in patients with diabetes it is much higher, between 16-40%. Thus, a point-of-care (POC) monitoring system to detect glycated albumin (GA) as a % of total serum albumin has been developed here. Specifically, a paper fluidic test to measure glycated and unglycated serum albumin has been developed that uses an aptamer-based assay with gold nanoparticles to produce colorimetric measurements. The assays were constructed using a sandwich aptamer format and colorimetric intensity was measured by scanning the capture layer of the paper fluidic device using a standard flatbed scanner followed by RGB analysis. The assays are able to determine the concentration of glycated and serum albumin in their physiologically relevant ranges of 50-300μM and 500-750μM. The paper fluidic system enabled the placement of gold nanoparticle probes in the device thereby automating the system and minimizing user intervention. Using aptamers as recognition elements and colorimetric transduction with gold nanoparticles, the system was shown, to possess the required sensitivity, selectivity, and dynamic range for physiologic monitoring.

Novel tools for malaria diagnosis, particularly rapid diagnostic tests (RDT’s), have provided alt... more Novel tools for malaria diagnosis, particularly rapid diagnostic tests (RDT’s), have provided alternatives to laboratory based microscopic disease confirmation. While RDT’s provide a disposable, low-cost option for parasite detection and some level of speciation, they fail to quantify parasitemia, which is useful in monitoring morbidity and identifying candidates for intensive treatment regimens. A low-cost microscope designed to gather quantitative parasitemia data from blood smears generated in microfluidic cartridges is presented. The system employs bi-modal imaging and uses components selected to optimize cost savings, system robustness, and optical performance. Bimodality is achieved by capturing two subsequent images for each field-of-view, with transmission-mode images providing cell counts and fluorescence-mode images providing biomarker localization data. A monochromatic LED for transmission illumination is employed with center wavelength aligned to the fluorophore label (a...

The use of mobile phones to conduct diagnostic microscopy at the point-of-care presents intriguin... more The use of mobile phones to conduct diagnostic microscopy at the point-of-care presents intriguing possibilities for the advancement of high-quality medical care in remote settings. However, it is challenging to create a single device that can adapt to the ever-varying camera technologies in phones or that can image with the customization that multiple modalities require for applications such as malaria diagnosis. A portable multi-modal microscope system is presented that utilizes a Raspberry Pi to collect and transmit data wirelessly to a myriad of electronic devices for image analysis. The microscopy system is capable of providing to the user correlated brightfield, polarized, and fluorescent images of samples fixed on traditional microscopy slides. The multimodal diagnostic capabilities of the microscope were assessed by measuring parasitemia of Plasmodium falciparum-infected thin blood smears. The device is capable of detecting fluorescently-labeled DNA using FITC excitation (49...

Coatings, 2021

This work focuses on the development of nanoparticle-based layer-by-layer (LbL) coatings for enha... more This work focuses on the development of nanoparticle-based layer-by-layer (LbL) coatings for enhancing the detection sensitivity and selectivity of volatile organic compounds (VOCs) using on-chip mid-infrared (MIR) waveguides (WGs). First, we demonstrate construction of conformal coatings of polymer/mesoporous silica nanoparticles (MSNs) on the surface of Si-based WGs using the LbL technique and evaluate the coating deposition conditions, such as pH and substrate withdrawal speed, on the thickness and homogeneity of the assemblies. We then use the modified WGs to achieve enhanced sensitivity and selectivity of polar organic compounds, such as ethanol, versus non-polar ones, such as methane, in the MIR region. In addition, using density functional theory calculations, we show that such an improvement in sensing performance is achieved due to preferential adsorption of ethanol molecules within MSNs in the vicinity of the WG evanescent field.

Optical Diagnostics and Sensing XVIII: Toward Point-of-Care Diagnostics, 2018

Research toward development of point-of-care (POC) technologies is emerging as a means for diagno... more Research toward development of point-of-care (POC) technologies is emerging as a means for diagnosis and monitoring of patients outside the hospital. These POC devices typically utilize assays capable of detecting low level biomarkers indicative of specific diseases. L-citrulline, an α-amino acid produced in the intestinal mucosa cells, is one such biomarker typically found circulating within the plasma at physiological concentrations of ~40 μM. Researchers have found that intestinal enterocyte malfunction causes its level to be significantly lowered, establishing it as a potential diagnostic biomarker for gut function. Our research group has proposed the development of a surface enhanced Raman spectroscopy (SERS) based assay, using vertical flow paper fluidics, for citrulline detection. The assay consists of a fluorescently active, Raman reporter labeled aptamer conjugated on gold nanoparticles. The aptamer changes its confirmation on binding to its target, which in turn changes the distance between the Raman active molecule and the nanoparticle surface. These particles were embedded within a portable chip consisting of cellulose-based paper. After the chips were loaded with different concentrations of free L-citrulline in phosphate buffer, time was given for the assay to interact with the sample. A handheld Raman spectrometer (638 nm; Ocean Optics) was used to measure the SERS intensity. Results showed decrease in intensity with increasing concentration of L-citrulline (0-50μM).

Journal of Biomedical Optics, 2019

The focus of this work is toward the development of a point-of-care (POC) handheld technology for... more The focus of this work is toward the development of a point-of-care (POC) handheld technology for the noninvasive early detection of salivary biomarkers. The initial of focus was the detection and quantification of S100 calcium-binding protein P (S100P) mRNA found in whole saliva for use as a potential biomarker for oral cancer. Specifically, a surface-enhanced Raman spectroscopy (SERS)-based approach and assay were designed, developed, and tested for sensitive and rapid detection of S100P mRNA. Gold nanoparticles (AuNPs) were conjugated with oligonucleotides and malachite green isothiocyanate was then used as a Raman reporter molecule. The hybridization of S100P target to DNA-conjugated AuNPs in sandwich assay format in both free solution and a vertical flow chip (VFC) was confirmed using a handheld SERS system. The detection limit of the SERS-based assay in free solution was determined to be 1.1 nM, whereas on the VFC the detection limit was observed to be 10 nM. SERS-based VFCs were also used to quantify the S100P mRNA from saliva samples of oral cancer patients and a healthy group. The result indicated that the amount of S100P mRNA detected for the oral cancer patients is three times higher than that of a healthy group.

Biomedical Optics Express, Jul 19, 2017

The quantification of visceral organ oxygenation after trauma-related systemic hypovolemia and sh... more The quantification of visceral organ oxygenation after trauma-related systemic hypovolemia and shock is critical to enable effective resuscitation. In this work, a photoplethysmography-based (PPG) sensor was specifically designed for probing the perfusion and oxygenation condition of intestinal tissue with the ultimate goal to monitor patients post trauma to guide resuscitation. Through Monte Carlo modeling, suitable optofluidic phantoms were determined, the wavelength and separation distance for the sensor was optimized, and sensor performance for the quantification of tissue perfusion and oxygenation was tested on the in-vitro phantom. In particular, the Monte Carlo simulated both a standard block three-layer model and a more realistic model including villi. Measurements were collected on the designed three layer optofluidic phantom and the results taken with the small form factor PPG device showed a marked improvement when using shorter visible wavelengths over the more conventional longer visible wavelengths. Overall, in this work a Monte Carlo model was developed, an optofluidic phantom was built, and a small form factor PPG sensor was developed and characterized using the phantom for perfusion and oxygenation over the visible wavelength range. The results show promise that this small form factor PPG sensor could be used as a future guide to shock-related resuscitation.

Microfluidics and Nanofluidics

Automated generation of a thin blood smear with a pumpless, capillary-driven, microfluidic would ... more Automated generation of a thin blood smear with a pumpless, capillary-driven, microfluidic would overcome the limitations of manually prepared smears and enable potential point-of-care (POC) applications. Herein, this was accomplished with microfluidic design that leveraged an amphiphilic silicone and channel pillars. The silicone (Sylgard 184) was combined with a surface-modifying additive (SMA), an amphiphilic poly(ethylene oxide) (PEO)-silane at varying concentrations (3, 5, and 7 wt%). The channels were formed with dimensions of 4.7 µm, 250 µm, and 16 mm (height × width × length, respectively). Pillar sections were added at the inlet, outlet and two interior sections to not only prevent channel collapse but to improve flow and cell distribution. After deposition of blood (0.3, 1, and 2 µL) to the channel inlet, the flow time and flow stop times were recorded and the channels imaged to assess smear uniformity and for automated cell counting. A thin blood smear was generated for microfluidic chips prepared with 5 wt% SMA and provided with 0.3 µL of blood.

The Analyst

A dual assay cartridge was developed and used in conjunction with a handheld reader for sensing %... more A dual assay cartridge was developed and used in conjunction with a handheld reader for sensing % glycated albumin to monitor gestational diabetes at home.

Journal of Biomedical Optics

Significance: Point-of-care (POC) platforms utilizing optical biosensing strategies can achieve o... more Significance: Point-of-care (POC) platforms utilizing optical biosensing strategies can achieve on-site detection of biomarkers to improve the quality of care for patients in low-resource settings. Aim: We aimed to develop a portable, multi-modal spectroscopic platform capable of performing Raman and fluorescence measurements from a single sample site. Approach: We designed the spectroscopic platform in OpticStudio using commercial optical components and built the system on a portable optical breadboard. Two excitation and collection arms were utilized to detect the two optical signals. The multi-modal functionality was validated using ratiometric Raman/fluorescence samples, and the potential utility was demonstrated using a model bioassay for cardiac troponin I. Results: The designed spectroscopic platform achieved a spectral resolution of 0.67 AE 0.2 nm across the Raman detection range (660 to 770 nm). The ratiometric Raman/fluorescence samples demonstrated no crosstalk between the two detector arms across a gradient of high molar concentrations. Testing of the model bioassay response showed that the integrated approach improved the linearity of the calibration curve from (R 2 ¼ 0.977) for the Raman only and (R 2 ¼ 0.972) for the fluorescence only to (R 2 ¼ 0.988) for the multi-modal approach. Conclusion: These findings demonstrate the potential impact of a multi-modal POC spectroscopic platform to improve the sensitivity and robustness necessary for biomarker detection.

Biosensors

Cardiovascular disease is the leading cause of death globally. To provide continuous monitoring o... more Cardiovascular disease is the leading cause of death globally. To provide continuous monitoring of blood pressure (BP), a parameter which has shown to improve health outcomes when monitored closely, many groups are trying to measure blood pressure via noninvasive photoplethysmography (PPG). However, the PPG waveform is subject to variation as a function of patient-specific and device factors and thus a platform to enable the evaluation of these factors on the PPG waveform and subsequent hemodynamic parameter prediction would enable device development. Here, we present a computational workflow that combines Monte Carlo modeling (MC), gaussian combination, and additive noise to create synthetic dataset of volar fingertip PPG waveforms representative of a diverse cohort. First, MC is used to determine PPG amplitude across age, skin tone, and device wavelength. Then, gaussian combination generates accurate PPG waveforms, and signal processing enables data filtration and feature extracti...

Analytical methods : advancing methods and applications, 2021

Effective staining of peripheral blood smears by increasing contrast of intracellular components ... more Effective staining of peripheral blood smears by increasing contrast of intracellular components and biomarkers is essential for the accurate characterization, diagnosis, and monitoring of various diseases such as malaria. To assess the potential for automation of stained whole human blood smears at the point-of-care (POC), brightfield and fluorescence staining protocols were adapted for smears generated in channels of pumpless microchannels and compared to a standard glass smear. A 3× concentration Giemsa brightfield staining solutions (10, 33, and 50% dilution), and Acridine Orange fluorescence staining solutions (12 μg mL-1) were evaluated with human blood smears containing malaria parasites within a microfluidic channel. Giemsa staining at 33% dilution showed an optimal combination of contrast and preservation of cellular morphology, while 50% dilutions showed significant cellular crenation and 10% dilutions did not show desired contrast in brightfield imaging. Fluorescence stai...

Nanoscale Advances, 2021

Here we report the synthesis of core–satellite nanoparticles to explore tunable SERS hot-spot gen... more Here we report the synthesis of core–satellite nanoparticles to explore tunable SERS hot-spot generation, signal reproducibility and long-term activity.

The Journal of Nutrition, 2001

With recent advancements in micro-fabrication and nano-fabrication techniques as well as advancem... more With recent advancements in micro-fabrication and nano-fabrication techniques as well as advancements in the photonics industry, there is now the potential to develop less invasive portable sensors for monitoring micronutrients and other substances used to assess overall health. There have been many technology innovations in the central laboratory for these substances for overall health status but the primary motivation for the research and development of a portable field instrument has come from a diabetic patient and market-driven desire to minimally invasively or noninvasively monitor glucose concentrations in vivo. Such a sensor system has the potential to significantly improve the quality of life for the estimated 16 million diabetics in this country by making routine glucose measurements less painful and more convenient. In addition, there is a critical need for the development of less invasive portable technologies to assess micronutrient status (iron, vitamin A, iodine and folate), environmental hazards (lead) and for other disease-related substances, such as billirubin for infant jaundice. Currently, over 100 small companies and universities are working to develop improved monitoring devices, primarily for glucose, and optical methods are a big part of these efforts. In this article many of these potentially less invasive and portable optical sensing technologies, which are currently under investigation, will be reviewed including optical absorption spectroscopy, polarimetry, Raman spectroscopy and fluorescence.

Biomedical Optical Spectroscopy and Diagnostics / Therapeutic Laser Applications, 1998

A system was developed using a Fourier Transform spectrometer configured for the near-infrared (2... more A system was developed using a Fourier Transform spectrometer configured for the near-infrared (2.0- 2.5 pm) range to investigate spectral differences between cancerous and normal oral tissue. Cancer was induced in the left or right cheek of hamsters. The animals were euthanized and cancerous as well as normal tissue was excised and analyzed in vitro. A total of 20 spectra were recorded 10 from cancerous tissue and 10 from normal tissue. Polynomial subtraction was used for preprocessing the raw spectral data. The preprocessed data were entered into a principal component analysis (PCA) algorithm which showed the ability to discriminate the tissue types across animals using this wavelength range.

... Valery V. Tuchin; Gregory E. Brill. New potentialities for noninvasive optical investigation ... more ... Valery V. Tuchin; Gregory E. Brill. New potentialities for noninvasive optical investigation of microcirculation in extended space missions. Author(s): Youri I. Gurfinkel; Valery M. Mikhailov. Computer simulation of the decay of nonlinear ...

Introduction to Biomedical Engineering, 2005

Publisher Summary This chapter provides students with a better understanding of the fundamental p... more Publisher Summary This chapter provides students with a better understanding of the fundamental principles associated with the growing field of biomedical optics as well as the design of optically based therapeutic, diagnostic, and monitoring devices. The chapter also describes the biochemical and biophysical interactions of optic and fiber optic systems with biological tissue and helps understand the photothermal interactions of laser systems with biological tissue. The propagation of light through biological media such as tissue begins with a simple ray optics approach for light traveling through a nonparticipating medium in which the effect of the absorption and scatter within the medium is ignored. The effects of absorption and scatter on light propagation have then been discussed along with the consideration of boundary conditions and various means of measuring the optical absorption and scattering properties.Several emerging imaging techniques are being developed by combining relatively transparent acoustic energy with strongly scattering light, which are called hybrid optical imaging. Ultrasound-modulated optical tomography, photoacoustic tomography, and sonoluminescence have been discussed.

Optics and Biophotonics in Low-Resource Settings V, 2019

Advances in consumer electronics and affordable high functioning optics have led to renewed inter... more Advances in consumer electronics and affordable high functioning optics have led to renewed interest in the development and application of portable microscopes for the remote diagnosis of diseases such as malaria. Indeed, better tools for malaria diagnosis are necessary to combat increasing rates of false-negative diagnosis and drug resistance. In this work, the capabilities and utility of a portable, multimodal microscopy system designed for malaria diagnosis are explored. The system, which combines off-the-shelf optical components with a Raspberry Pi for data collection and a microfluidic cartridge for sample preparation, is capable of capturing brightfield, fluorescent, and cross-polarized images of thin blood smears. Parameters for each imaging modality are defined and related to their potential diagnostic utility. Samples of Plasmodium falciparum cultures were stained either with fluorophores or with a dual Giemsa-fluorophore procedure and examined using the portable and gold-standard microscopes. Preliminary results indicate that the microscope is capable of nearly diffraction limited performance and can distinguish rings, trophozoites, and schizonts in fluorescence and brightfield modes along with hemozoin crystals in cross-polarized mode. Parasitemia measurements for simulated mixed-stage, severe infections show strong agreement with Giemsa-stained gold-standard measurements. If cost and durability limitations can be overcome, this microscopy system may be able to augment malaria-screening rapid diagnostic tests to enable the more precise distribution of antimalarial medications at the point-of-care.

Optical Diagnostics and Sensing XXI: Toward Point-of-Care Diagnostics, 2021

Gestational diabetes mellitus (GDM) affects between 2-14% of pregnant women in the United States ... more Gestational diabetes mellitus (GDM) affects between 2-14% of pregnant women in the United States every year. The glycated version of serum albumin, the most abundant protein in blood, owing to its half-life of ~21 days can effectively be used as an intermediate biomarker for monitoring GDM. Normal level of glycation of albumin is between 10-16% whereas in patients with diabetes it is much higher, between 16-40%. Thus, a point-of-care (POC) monitoring system to detect glycated albumin (GA) as a % of total serum albumin has been developed here. Specifically, a paper fluidic test to measure glycated and unglycated serum albumin has been developed that uses an aptamer-based assay with gold nanoparticles to produce colorimetric measurements. The assays were constructed using a sandwich aptamer format and colorimetric intensity was measured by scanning the capture layer of the paper fluidic device using a standard flatbed scanner followed by RGB analysis. The assays are able to determine the concentration of glycated and serum albumin in their physiologically relevant ranges of 50-300μM and 500-750μM. The paper fluidic system enabled the placement of gold nanoparticle probes in the device thereby automating the system and minimizing user intervention. Using aptamers as recognition elements and colorimetric transduction with gold nanoparticles, the system was shown, to possess the required sensitivity, selectivity, and dynamic range for physiologic monitoring.

Novel tools for malaria diagnosis, particularly rapid diagnostic tests (RDT’s), have provided alt... more Novel tools for malaria diagnosis, particularly rapid diagnostic tests (RDT’s), have provided alternatives to laboratory based microscopic disease confirmation. While RDT’s provide a disposable, low-cost option for parasite detection and some level of speciation, they fail to quantify parasitemia, which is useful in monitoring morbidity and identifying candidates for intensive treatment regimens. A low-cost microscope designed to gather quantitative parasitemia data from blood smears generated in microfluidic cartridges is presented. The system employs bi-modal imaging and uses components selected to optimize cost savings, system robustness, and optical performance. Bimodality is achieved by capturing two subsequent images for each field-of-view, with transmission-mode images providing cell counts and fluorescence-mode images providing biomarker localization data. A monochromatic LED for transmission illumination is employed with center wavelength aligned to the fluorophore label (a...

The use of mobile phones to conduct diagnostic microscopy at the point-of-care presents intriguin... more The use of mobile phones to conduct diagnostic microscopy at the point-of-care presents intriguing possibilities for the advancement of high-quality medical care in remote settings. However, it is challenging to create a single device that can adapt to the ever-varying camera technologies in phones or that can image with the customization that multiple modalities require for applications such as malaria diagnosis. A portable multi-modal microscope system is presented that utilizes a Raspberry Pi to collect and transmit data wirelessly to a myriad of electronic devices for image analysis. The microscopy system is capable of providing to the user correlated brightfield, polarized, and fluorescent images of samples fixed on traditional microscopy slides. The multimodal diagnostic capabilities of the microscope were assessed by measuring parasitemia of Plasmodium falciparum-infected thin blood smears. The device is capable of detecting fluorescently-labeled DNA using FITC excitation (49...

Coatings, 2021

This work focuses on the development of nanoparticle-based layer-by-layer (LbL) coatings for enha... more This work focuses on the development of nanoparticle-based layer-by-layer (LbL) coatings for enhancing the detection sensitivity and selectivity of volatile organic compounds (VOCs) using on-chip mid-infrared (MIR) waveguides (WGs). First, we demonstrate construction of conformal coatings of polymer/mesoporous silica nanoparticles (MSNs) on the surface of Si-based WGs using the LbL technique and evaluate the coating deposition conditions, such as pH and substrate withdrawal speed, on the thickness and homogeneity of the assemblies. We then use the modified WGs to achieve enhanced sensitivity and selectivity of polar organic compounds, such as ethanol, versus non-polar ones, such as methane, in the MIR region. In addition, using density functional theory calculations, we show that such an improvement in sensing performance is achieved due to preferential adsorption of ethanol molecules within MSNs in the vicinity of the WG evanescent field.

Optical Diagnostics and Sensing XVIII: Toward Point-of-Care Diagnostics, 2018

Research toward development of point-of-care (POC) technologies is emerging as a means for diagno... more Research toward development of point-of-care (POC) technologies is emerging as a means for diagnosis and monitoring of patients outside the hospital. These POC devices typically utilize assays capable of detecting low level biomarkers indicative of specific diseases. L-citrulline, an α-amino acid produced in the intestinal mucosa cells, is one such biomarker typically found circulating within the plasma at physiological concentrations of ~40 μM. Researchers have found that intestinal enterocyte malfunction causes its level to be significantly lowered, establishing it as a potential diagnostic biomarker for gut function. Our research group has proposed the development of a surface enhanced Raman spectroscopy (SERS) based assay, using vertical flow paper fluidics, for citrulline detection. The assay consists of a fluorescently active, Raman reporter labeled aptamer conjugated on gold nanoparticles. The aptamer changes its confirmation on binding to its target, which in turn changes the distance between the Raman active molecule and the nanoparticle surface. These particles were embedded within a portable chip consisting of cellulose-based paper. After the chips were loaded with different concentrations of free L-citrulline in phosphate buffer, time was given for the assay to interact with the sample. A handheld Raman spectrometer (638 nm; Ocean Optics) was used to measure the SERS intensity. Results showed decrease in intensity with increasing concentration of L-citrulline (0-50μM).

Journal of Biomedical Optics, 2019

The focus of this work is toward the development of a point-of-care (POC) handheld technology for... more The focus of this work is toward the development of a point-of-care (POC) handheld technology for the noninvasive early detection of salivary biomarkers. The initial of focus was the detection and quantification of S100 calcium-binding protein P (S100P) mRNA found in whole saliva for use as a potential biomarker for oral cancer. Specifically, a surface-enhanced Raman spectroscopy (SERS)-based approach and assay were designed, developed, and tested for sensitive and rapid detection of S100P mRNA. Gold nanoparticles (AuNPs) were conjugated with oligonucleotides and malachite green isothiocyanate was then used as a Raman reporter molecule. The hybridization of S100P target to DNA-conjugated AuNPs in sandwich assay format in both free solution and a vertical flow chip (VFC) was confirmed using a handheld SERS system. The detection limit of the SERS-based assay in free solution was determined to be 1.1 nM, whereas on the VFC the detection limit was observed to be 10 nM. SERS-based VFCs were also used to quantify the S100P mRNA from saliva samples of oral cancer patients and a healthy group. The result indicated that the amount of S100P mRNA detected for the oral cancer patients is three times higher than that of a healthy group.

Monte Carlo modeling of photon propagation has been used in the examination of particular areas o... more Monte Carlo modeling of photon propagation has been used in the examination of particular areas of the body to further enhance the understanding of light propagation through tissue. This work seeks to improve upon the established simulation methods through more accurate representations of the simulated tissues in the wrist as well as the characteristics of the light source. The Monte Carlo simulation program was developed using Matlab. Generation of different tissue domains, such as muscle, vasculature, and bone, was performed in Solidworks, where each domain was saved as a separate .stl file that was read into the program. The light source was altered to give considerations to both viewing angle of the simulated LED as well as the nominal diameter of the source. It is believed that the use of these more accurate models generates results that more closely match those seen in-vivo, and can be used to better guide the design of optical wrist-worn measurement devices.