Gerard Coté - Profile on Academia.edu (original) (raw)
Papers by Gerard Coté
Journal of Biomedical Optics, Sep 8, 2020
Significance: Cardiac troponin I (cTnI) is a primary biomarker for diagnosis of myocardial infarc... more Significance: Cardiac troponin I (cTnI) is a primary biomarker for diagnosis of myocardial infarction (MI). In contrast to central laboratory tests for cTnI, point-of-care (POC) testing has the advantage of providing results when the patient is first encountered, which helps high-risk patients to be treated more rapidly and low-risk patients to be released in a timely fashion. A paper fluidic platform is good for POC testing because the paper is abundant, low cost, and disposable. However, current cTnI assays on paper platforms use antibodies as the recognition element, which has limitations due to the high cost of production and antibody stability issues at the POC. Aim: To develop an aptamer-based assay on a paper strip using surface-enhanced resonance Raman spectroscopy (SERRS) for detection of cTnI in the clinically relevant range at the POC. Approach: Gold nanoparticles (AuNPs) were functionalized with a Raman reporter molecule, malachite green isothiocyanate. The functionalized AuNPs were encapsulated in a silica shell and provided a SERRS signal using a handheld Raman system with a 638-nm excitation wavelength. A primary aptamer and a secondary aptamer of cTnI were used in a sandwich assay format to bind the cTnI on a test line of a paper fluidic platform. By measuring the SERRS signal from the test line, the concentration of cTnI was quantitatively determined. The aptamer-based SERRS assay on a paper strip had a detection range of 0.016 to 0.1 ng∕ml for cTnI, had good selectivity for cTnI compared to three other markers, had good stability over 10 days, and had good performance in the more complex serum sample matrix. The aptamer-based SERRS assay on a paper strip has the potential to provide a sensitive, selective, stable, repeatable, and cost-effective platform for the detection of cTnI toward eventual use in diagnosis of MI at the POC.
Toward a multi-modal Raman and fluorescence spectroscopic platform at the point-of-care
Point-of-care (PoC) devices are gaining more attention due to their rapid readout times, low cost... more Point-of-care (PoC) devices are gaining more attention due to their rapid readout times, low cost and reduced system complexity. The use of these devices to aid in health outcomes, particularly of populations that lack access to centralized healthcare, is essential to improving quality of life. Broad fluorescence background presents a major issue in Raman detection with suppression techniques being employed to prevent signal crosstalk. The presented spectroscopic platform splits the Raman and fluorescence signal onto separate detectors in order in minimize crosstalk and to extract useful information from each optical signal. Separate illumination sources were utilized to selectively excite either Raman or fluorescence emission. The developed spectroscopic platform was designed using off-the-shelf components with small form factor and ultimately the capacity for low cost being the primary selection criteria. The platform enables multimodal detection of Raman signal over a spectral range of 900 – 2000 cm-1 with a resolution of 2 nm, coupled with monitoring the average fluorescence emission intensity. The ratio of the two signals is compared in order to quantify the concentration of target molecules present. The optical system was assembled on a portable optical breadboard and calibrated using an Argon emission lamp. The multimodal functionality was validated using Raman reporter (4-MBA) tagged gold nanoparticles in solution with unbound fluorophores (fluorescein). Results showed an increase in both the Raman and fluorescence signals as the concentration of each was increased from 5-55 μM.
Surface-enhanced Raman spectroscopy for the detection of pathogenic DNA and protein in foods
Proceedings of SPIE, Jul 24, 2003
Traditional Raman spectroscopy while extremely sensitive to structure and conformation, is an ine... more Traditional Raman spectroscopy while extremely sensitive to structure and conformation, is an ineffective tool for the detection of bioanalytes at the sub milimolar level. Surface Enhanced Raman Spectroscopy (SERS) is a technique developed more recently that has been used with applaudable success to enhance the Raman cross-section of a molecule by factors of 106 to 1014. This technique can be exploited in a nanoscale biosensor for the detection of pathogenic proteins and DNA in foods by using a biorecognition molecule to bring a target analyte in close proximity to the mental surface. This is expected to produce a SERS signal of the target analyte, thus making it possible to easily discriminate between the target analyte and possible confounders. In order for the sensor to be effective, the Raman spectra of the target analyte would have to be distinct from that of the biorecognition molecule, as both would be in close proximity to the metal surface and thus be subjected to the SERS effect. In our preliminary studies we have successfully used citrate reduced silver colloidal particles to obtain unique SERS spectra of alpha-helical and beta-sheet bovine serum albumin (BSA) that served as models of an alpha helical antiobiody (biorecognition element) and a beta-sheet target protein (pathogenic prion). In addition, the unique SERS spectra of double stranded and single stranded DNA were also obtained where the single stranded DNA served as the model for the biorecognition element and the double stranded DNA served as themodel for the DNA probe/target hybrid. This provides a confirmation of the feasibility of the method which opens opportunities for potentially wide spread applications in the detection of food pathogens, biowarefare agents, andother bio-analytes.
Biomaterials, Aug 1, 2008
β-Amyloid peptide (Aβ), the primary protein component in senile plaques associated with Alzheimer... more β-Amyloid peptide (Aβ), the primary protein component in senile plaques associated with Alzheimer's disease (AD), has been implicated in neurotoxicity associated with AD. Previous studies have shown that the Aβ-neuronal membrane interaction plays a crucial role in Aβ toxicity. More specifically, it is thought that Aβ interacts with ganglioside rich and sialic acid rich regions of cell surfaces. In light of such evidence, we have hypothesized that the Aβ-membrane sialic acid interaction could be inhibited through use of a biomimic multivalent sialic acid compound that would compete with the cell surface for Aβ binding. To explore this hypothesis, we synthesized a series of photocrosslinked sialic acid containing oligosaccharides and tested their ability to bind Aβ and attenuate Aβ toxicity in cell culture assays. We show that a polymer prepared via the photocrosslinking of disialyllacto-N-tetraose (DSLNT) was able to attenuate Aβ toxicity at low micromolar concentrations without adversely affecting the cell viability. Polymers prepared from mono-sialyl-oligosaccharides were less effective at Aβ toxicity attenuation. These results demonstrate the feasibility of using photocrosslinked sialyl-oligosaccharides for prevention of Aβ toxicity in vitro and may provide insight into the design of new materials for use in attenuation of Aβ toxicity associated with AD.
Applied Spectroscopy, 2002
Current techniques for m onitoring glucose concentration during cell culture are invasively perfo... more Current techniques for m onitoring glucose concentration during cell culture are invasively performed using an off-line measurement system . Even though in situ or ex situ analyte sensors have been tried for on-line measurement, they suffer from dif culties including the inability to keep them sterile, their limited lifetime, and their lack of stability. In this resea rch an alternative optical noninvasive on-line monitoring system based on near-infrared absorbance spectroscopy was developed to m easure glucose concentration of cell culture m edia in a rotary cell culture system. The system included an automatic sampling component controlled by a LabVIEW program and a high-throughput ber coupling com ponent connected to a Fourier transform near-infrared spectrom eter. The effectiveness of the system was investigated via noninvasive on-line measurem ent of glucose absorbance spectra in the cell culture media during T-cell culture. Glucose absorbance spectra were collected in the spectra l range of 2.0 to 2.5 mm. Partial least-squares regression was employed to build a successful multivariate calibration model. The standard error of prediction and mean percent error for glucose were 7.7 mg/dL and 1.0%, respectively. The successful resu lts represent an im portant step in the development of a noninvasive, closed-loop, system for monitoring analytes in cell culture.
Journal of Biomedical Optics, 1997
In order to enhance cell culture growth in bioreactors, biosensors such as those used for glucose... more In order to enhance cell culture growth in bioreactors, biosensors such as those used for glucose detection must be developed that are capable of monitoring cell culture processes continuously and preferably noninvasively. The development of a unique noninvasive, optically based polarimetric glucose sensor is reported. The data were collected using a highly sensitive, lab-built polarimeter with digital feedback and a red laser diode source. A range of glucose concentrations was evaluated using both glucose-doped double-distilled water and a bovine serum-based medium. The serum-based medium is the nutritional environment in which the cell cultures are grown. Both media were examined across two glucose concentration ranges-a lower range of 100 mg/dl in 10-mg/dl increments and a higher range up to 600 mg/dl in 50-mg/dl increments. The linear regression in all experiments yielded standard errors of prediction of less than 8.5 mg/dl across both ranges.
Analytical Chemistry, May 28, 2020
Raman spectroscopy using aluminum nitride (AlN) optical waveguides was demonstrated for organic c... more Raman spectroscopy using aluminum nitride (AlN) optical waveguides was demonstrated for organic compound analysis. The AlN waveguide device was prepared by reactive sputtering deposition and complementary-metal-oxide semiconductor (CMOS) processes. A fundamental waveguide mode was observed over a broad visible spectrum and the waveguide evanescent wave was used to excite the Raman signals of the test analytes. The performance of the waveguide sensor was characterized by measuring the Raman spectra of the benzene derivative mixtures consisting of benzene, anisole, and toluene. The compositions and concentrations were resolved by correlating the obtained Raman spectrum with the characteristic Raman peaks associated with C-C, C-H, and C-O functional groups. With the advantages of real-time detection and enhanced Raman signal intensity, the AlN waveguides provided a sensor platform for non-destructive and on-line chemical compound monitoring.
Exploring the Clinical Utility of Raman Spectroscopy for Point-of-Care Cardiovascular Disease Biomarker Detection
Applied Spectroscopy, Jul 24, 2023
A variety of innovative point-of-care (POC) solutions using Raman systems have been explored. How... more A variety of innovative point-of-care (POC) solutions using Raman systems have been explored. However, the vast effort is in assay development, while studies of the characteristics required for Raman spectrometers to function in POC applications are lacking. In this study, we tested and compared the performance of eight commercial Raman spectrometers ranging in size from benchtop Raman microscopes to portable and handheld Raman spectrometers using paper fluidic cartridges, including their ability to detect cardiac troponin I and heart fatty acid binding protein, both of which are well-established biomarkers for evaluating cardiovascular health. Each spectrometer was evaluated in terms of excitation wavelength, laser characteristics, and ease of use to investigate POC utility. We found that the Raman spectrometers equipped with 780 and 785 nm laser sources exhibited a reduced background signal and provided higher sensitivity compared to those with 633 and 638 nm laser sources. Furthermore, the spectrometer equipped with the single acquisition line readout functionality showed improved performance when compared to the point scan spectrometers and allowed measurements to be made faster and easier. The portable and handheld spectrometers also showed similar detection sensitivity to the gold standard instrument. Lastly, we reduced the laser power for the spectrometer with single acquisition line readout capability to explore the system performance at a laser power that change the classification from a Class 3B laser device to a Class 3R device and found that it showed comparable performance. Overall, these findings show that portable Raman spectrometers have the potential to be used in POC settings with accuracy comparable to laboratory-grade instruments, are relatively low-cost, provide fast signal readout, are easy to use, and can facilitate access for underserved communities.
Optical waveguides for on-chip fluorescence measurements (Conference Presentation)
Optical Diagnostics and Sensing XIX: Toward Point-of-Care Diagnostics, 2019
Optical waveguides using a visible transparent nitride were developed to perform fluorescence mea... more Optical waveguides using a visible transparent nitride were developed to perform fluorescence measurement on a chip. Through finite difference time domain (FDTD) design, the exciting green light was guided by the micron-scale ridge waveguide, while its evanescent wave was expanded outside the waveguide surface and capable to efficiently excite the fluorescent molecules that were approaching the waveguide facets. Since the waveguide was centimeters long, it has a longer fluorescence excitation path comparing to traditional samples prepared for microscopy measurements. As result, the waveguide device can excite stronger fluorescent signals. In addition, the nitride waveguide was prepared by the complementary metal–oxide–semiconductor (CMOS) process thus enabling high volume manufacturing and reducing the cost of the device fabrication. The AlN waveguide was then integrated with a microfluidic devices to experimentally demonstrate real-time fluorescence detection. Solution samples with different dye concentrations were sequentially injected into the microfluidic chamber. By recording the emission signals, we showed that the fluorescent signals were consistently amplified as the dye concentrations increased. In addition, real-time fluorescence detection with a response time less than seconds was achieved. The developed waveguide based fluorescence measurement provides a new miniaturized platform for low cost and highly accurate point-of-care application.
Journal of biomedical optics, 2018
DNA-functionalized nanoparticles, when paired with surface-enhanced Raman spectroscopy (SERS), ca... more DNA-functionalized nanoparticles, when paired with surface-enhanced Raman spectroscopy (SERS), can rapidly detect microRNA. However, widespread use of this approach is hindered by drawbacks associated with large and expensive benchtop Raman microscopes. MicroRNA-17 (miRNA-17) has emerged as a potential epigenetic indicator of preeclampsia, a condition that occurs during pregnancy. Biomarker detection using an SERS point-of-care device could enable prompt diagnosis and prevention as early as the first trimester. Recently, strides have been made in developing portable Raman systems for field applications. An SERS assay for miRNA-17 was assessed and translated from traditional benchtop Raman microscopes to a handheld system. Three different photoactive molecules were compared as potential Raman reporter molecules: a chromophore, malachite green isothiocyanate (MGITC), a fluorophore, tetramethylrhodamine isothiocyanate, and a polarizable small molecule 5,5-dithio-bis-(2-nitrobenzoic aci...
Journal of biomedical optics, Jul 1, 2017
A point-of-care (PoC) device with the ability to detect biomarkers at low concentrations in bodil... more A point-of-care (PoC) device with the ability to detect biomarkers at low concentrations in bodily fluids would have an enormous potential for medical diagnostics outside the central laboratory. One method to monitor analytes at low concentrations is by using surface-enhanced Raman spectroscopy (SERS). In this preliminary study toward using SERS for PoC biosensing, the surface of colloidal silver (Ag) nanocubes has been modified to test the feasibility of a competitive binding SERS assay utilizing aptamers against citrulline. Specifically, Ag nanocubes were functionalized with mercaptobenzoic acid, as well as a heterobifunctional polyethylene glycol linker that forms an amide bond with the amino acid citrulline. After the functionalization, the nanocubes were characterized by zeta-potential, transmission electron microscopy images, ultraviolet/visible spectroscopy, and by SERS. The citrulline aptamers were developed and tested using backscattering interferometry. The data show that ...
Journal of biomedical optics, Aug 1, 2016
A micro- to nanochannel nanoparticle aggregating device that does not require any input energy to... more A micro- to nanochannel nanoparticle aggregating device that does not require any input energy to organize the particles to a specific location, i.e., no pumps, plugs, heat, or magnets, has been designed and used to characterize the surface-enhanced Raman spectroscopy (SERS) signal from four unique functionalized nanoparticles (gold, silver-gold nanocages, silver nanocubes, and silica-gold nanoshells). The SERS signal was assessed in terms of the peak signal strength from the four different Raman reporter functionalized nanoparticles to determine which nanoparticle had better utility in the channel to provide the most robust platform for a future biological analyte detection device. The innovation used to fabricate the micro- to nanochannel device is described; the TEM images of the nanoparticles are shown; the absorption data for the nanoparticles are given; and the spectral data for the Raman reporter, mercaptobenzoic acid (MBA), are depicted. In the micro- to nanochannel describe...
Monte Carlo modeling of spatially complex wrist tissue for the optimization of optical pulse oximeters
SPIE Proceedings, 2017
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.
SPIE Proceedings, 2014
To non-invasively measure glucose concentrations across the aqueous humor of the eye, a high-spee... more To non-invasively measure glucose concentrations across the aqueous humor of the eye, a high-speed, dual-wavelength optical polarimetric approach is proposed that addresses a key limitation of prior set-ups -system response time -while compensating for time-varying motion artifact due to corneal birefringence. This research is made up of three goals. The first goal is to design and construct a high-frequency, ferrite core Faraday rotator that can both rotate and modulate linearly polarized light in a frequency range of 30 to 75 kHz. The second goal is to implement a single ferrite core Faraday rotator into the current polarimetric approach. The third goal is to replace three air-core Faraday rotators with two ferrite core Faraday rotators for both modulation and compensation, allowing for two different signals to be measured on a single photodetector. In vitro phantom studies are performed with and without motion artifact. The sensor is shown to stabilize in ~2 msec and provide standard errors for glucose concentration of less than 13 mg/dL in the presence of motion. The results indicate that higher frequency modulation can reduce the overall system stabilization time with minimal loss of accuracy in the presence of motion artifact. Dr. Prasad Enjeti, for their support and their time. Their guidance through theory and design pointed me in the right directions. Mr. Erwin Thomas III and Dr. Bilal Malik both guided me in new and interesting directions as well. Thanks also go to my friends, including but not limited to Casey Pirnstill, Tony Akl, Zhen Fang, Brian Cummins, Haley Marks, Javier Garza, and Andrea Locke. They have all been helpful during these past few years. Finally, I'd like to acknowledge my family, including but not limited to my mom, who never gave up on my education, my sister, who gave me the best advice and support, my brother, who has always supported me in whatever I do, and my girlfriend, who supported me when I needed it the most.
Nanoparticle based biosensor for the detection of BSE in foods
The use of surface enhanced Raman spectroscopy (SERS) in a competitive affinity binding assay for the detection of prions
Annual International Conference of the IEEE Engineering in Medicine and Biology Society, 2003
The recent reports of spread of transmissible spongiform encephalopathies such as bovine spongifo... more The recent reports of spread of transmissible spongiform encephalopathies such as bovine spongiform encephalopathy to humans has led to the need to develop rapid and sensitive methods* for the detection for the infectious agent of these diseases, prions, in a variety of biological samples. A novel surface enhanced Raman spectroscopy (SERS) based method has been developed for the detection of
In vitro detection of beta amyloid exploiting surface enhanced Raman scattering (SERS) using a nanofluidic biosensor
SPIE Proceedings, 2008
... In vitro detection of beta amyloid exploiting surface enhanced Raman scattering (SERS) using ... more ... In vitro detection of beta amyloid exploiting surface enhanced Raman scattering (SERS) using a nanofluidic biosensor (Proceedings Paper). ... Alzheimer's disease (AD), a neurodegenerative disease and the most common cause of dementia, affects 4.5 million people ...
A surface enhanced Raman spectroscopy platform based on nanoshells for detection of β-amyloid
SPIE Proceedings, 2008
A major limitation of many surfaced enhanced Raman spectroscopy (SERS) approaches is the dependen... more A major limitation of many surfaced enhanced Raman spectroscopy (SERS) approaches is the dependence of the Raman enhancement on the local nanostructure. While these local "hot spots" may provide areas of extremely strong enhancement, which make trace analyte detection possible, they also make quantitative measurements problematic. Gold nanoshells however, with the ratio of the radius of their silica core to
Functionalized nanoparticles for measurement of biomarkers using a SERS nanochannel platform
SPIE Proceedings, 2010
The overall goal of this research is to develop a new point-of-care system for early detection an... more The overall goal of this research is to develop a new point-of-care system for early detection and characterization of cardiac markers to aid in diagnosis of acute coronary syndrome. The envisioned final technology platform incorporates functionalized gold colloidal nanoparticles trapped at the entrance to a nanofluidic device providing a robust means for analyte detection at trace levels using surface enhanced
Journal of Biomedical Optics, 2006
Current research has revealed the importance of a class of cell surface proteins called integrins... more Current research has revealed the importance of a class of cell surface proteins called integrins in various vital physiological functions such as blood clotting, regulation of blood pressure, tissue blood flow, and vascular remodeling. The key to integrin functionality is its ability to mediate force transmission by interacting with the extracellular matrix and cytoskeleton. In addition, they play a role in signal transduction via their connection with the proteins in focal adhesion ͑FA͒ points. To understand the complex mechanism of cell-cell and cell-extracellular matrix ͑ECM͒ adhesion that is responsible for these diverse biochemical interactions, it is necessary to identify the integrins on cells and monitor their interaction with various ligands. To this end, for the first time, we employ surface-enhanced Raman spectroscopy ͑SERS͒ to detect integrins. The results show the capability using SERS to detect the integrins to the nanomolar concentration regime and to distinguish between two different kinds of integrins, ␣V3 and ␣51, that are present in vascular smooth muscle cells ͑VSMCs͒. It is anticipated that the SERS approach will potentially help elucidate the mechanism of integrin-ligand interactions in a variety of phenomena of physiological importance.
Journal of Biomedical Optics, Sep 8, 2020
Significance: Cardiac troponin I (cTnI) is a primary biomarker for diagnosis of myocardial infarc... more Significance: Cardiac troponin I (cTnI) is a primary biomarker for diagnosis of myocardial infarction (MI). In contrast to central laboratory tests for cTnI, point-of-care (POC) testing has the advantage of providing results when the patient is first encountered, which helps high-risk patients to be treated more rapidly and low-risk patients to be released in a timely fashion. A paper fluidic platform is good for POC testing because the paper is abundant, low cost, and disposable. However, current cTnI assays on paper platforms use antibodies as the recognition element, which has limitations due to the high cost of production and antibody stability issues at the POC. Aim: To develop an aptamer-based assay on a paper strip using surface-enhanced resonance Raman spectroscopy (SERRS) for detection of cTnI in the clinically relevant range at the POC. Approach: Gold nanoparticles (AuNPs) were functionalized with a Raman reporter molecule, malachite green isothiocyanate. The functionalized AuNPs were encapsulated in a silica shell and provided a SERRS signal using a handheld Raman system with a 638-nm excitation wavelength. A primary aptamer and a secondary aptamer of cTnI were used in a sandwich assay format to bind the cTnI on a test line of a paper fluidic platform. By measuring the SERRS signal from the test line, the concentration of cTnI was quantitatively determined. The aptamer-based SERRS assay on a paper strip had a detection range of 0.016 to 0.1 ng∕ml for cTnI, had good selectivity for cTnI compared to three other markers, had good stability over 10 days, and had good performance in the more complex serum sample matrix. The aptamer-based SERRS assay on a paper strip has the potential to provide a sensitive, selective, stable, repeatable, and cost-effective platform for the detection of cTnI toward eventual use in diagnosis of MI at the POC.
Toward a multi-modal Raman and fluorescence spectroscopic platform at the point-of-care
Point-of-care (PoC) devices are gaining more attention due to their rapid readout times, low cost... more Point-of-care (PoC) devices are gaining more attention due to their rapid readout times, low cost and reduced system complexity. The use of these devices to aid in health outcomes, particularly of populations that lack access to centralized healthcare, is essential to improving quality of life. Broad fluorescence background presents a major issue in Raman detection with suppression techniques being employed to prevent signal crosstalk. The presented spectroscopic platform splits the Raman and fluorescence signal onto separate detectors in order in minimize crosstalk and to extract useful information from each optical signal. Separate illumination sources were utilized to selectively excite either Raman or fluorescence emission. The developed spectroscopic platform was designed using off-the-shelf components with small form factor and ultimately the capacity for low cost being the primary selection criteria. The platform enables multimodal detection of Raman signal over a spectral range of 900 – 2000 cm-1 with a resolution of 2 nm, coupled with monitoring the average fluorescence emission intensity. The ratio of the two signals is compared in order to quantify the concentration of target molecules present. The optical system was assembled on a portable optical breadboard and calibrated using an Argon emission lamp. The multimodal functionality was validated using Raman reporter (4-MBA) tagged gold nanoparticles in solution with unbound fluorophores (fluorescein). Results showed an increase in both the Raman and fluorescence signals as the concentration of each was increased from 5-55 μM.
Surface-enhanced Raman spectroscopy for the detection of pathogenic DNA and protein in foods
Proceedings of SPIE, Jul 24, 2003
Traditional Raman spectroscopy while extremely sensitive to structure and conformation, is an ine... more Traditional Raman spectroscopy while extremely sensitive to structure and conformation, is an ineffective tool for the detection of bioanalytes at the sub milimolar level. Surface Enhanced Raman Spectroscopy (SERS) is a technique developed more recently that has been used with applaudable success to enhance the Raman cross-section of a molecule by factors of 106 to 1014. This technique can be exploited in a nanoscale biosensor for the detection of pathogenic proteins and DNA in foods by using a biorecognition molecule to bring a target analyte in close proximity to the mental surface. This is expected to produce a SERS signal of the target analyte, thus making it possible to easily discriminate between the target analyte and possible confounders. In order for the sensor to be effective, the Raman spectra of the target analyte would have to be distinct from that of the biorecognition molecule, as both would be in close proximity to the metal surface and thus be subjected to the SERS effect. In our preliminary studies we have successfully used citrate reduced silver colloidal particles to obtain unique SERS spectra of alpha-helical and beta-sheet bovine serum albumin (BSA) that served as models of an alpha helical antiobiody (biorecognition element) and a beta-sheet target protein (pathogenic prion). In addition, the unique SERS spectra of double stranded and single stranded DNA were also obtained where the single stranded DNA served as the model for the biorecognition element and the double stranded DNA served as themodel for the DNA probe/target hybrid. This provides a confirmation of the feasibility of the method which opens opportunities for potentially wide spread applications in the detection of food pathogens, biowarefare agents, andother bio-analytes.
Biomaterials, Aug 1, 2008
β-Amyloid peptide (Aβ), the primary protein component in senile plaques associated with Alzheimer... more β-Amyloid peptide (Aβ), the primary protein component in senile plaques associated with Alzheimer's disease (AD), has been implicated in neurotoxicity associated with AD. Previous studies have shown that the Aβ-neuronal membrane interaction plays a crucial role in Aβ toxicity. More specifically, it is thought that Aβ interacts with ganglioside rich and sialic acid rich regions of cell surfaces. In light of such evidence, we have hypothesized that the Aβ-membrane sialic acid interaction could be inhibited through use of a biomimic multivalent sialic acid compound that would compete with the cell surface for Aβ binding. To explore this hypothesis, we synthesized a series of photocrosslinked sialic acid containing oligosaccharides and tested their ability to bind Aβ and attenuate Aβ toxicity in cell culture assays. We show that a polymer prepared via the photocrosslinking of disialyllacto-N-tetraose (DSLNT) was able to attenuate Aβ toxicity at low micromolar concentrations without adversely affecting the cell viability. Polymers prepared from mono-sialyl-oligosaccharides were less effective at Aβ toxicity attenuation. These results demonstrate the feasibility of using photocrosslinked sialyl-oligosaccharides for prevention of Aβ toxicity in vitro and may provide insight into the design of new materials for use in attenuation of Aβ toxicity associated with AD.
Applied Spectroscopy, 2002
Current techniques for m onitoring glucose concentration during cell culture are invasively perfo... more Current techniques for m onitoring glucose concentration during cell culture are invasively performed using an off-line measurement system . Even though in situ or ex situ analyte sensors have been tried for on-line measurement, they suffer from dif culties including the inability to keep them sterile, their limited lifetime, and their lack of stability. In this resea rch an alternative optical noninvasive on-line monitoring system based on near-infrared absorbance spectroscopy was developed to m easure glucose concentration of cell culture m edia in a rotary cell culture system. The system included an automatic sampling component controlled by a LabVIEW program and a high-throughput ber coupling com ponent connected to a Fourier transform near-infrared spectrom eter. The effectiveness of the system was investigated via noninvasive on-line measurem ent of glucose absorbance spectra in the cell culture media during T-cell culture. Glucose absorbance spectra were collected in the spectra l range of 2.0 to 2.5 mm. Partial least-squares regression was employed to build a successful multivariate calibration model. The standard error of prediction and mean percent error for glucose were 7.7 mg/dL and 1.0%, respectively. The successful resu lts represent an im portant step in the development of a noninvasive, closed-loop, system for monitoring analytes in cell culture.
Journal of Biomedical Optics, 1997
In order to enhance cell culture growth in bioreactors, biosensors such as those used for glucose... more In order to enhance cell culture growth in bioreactors, biosensors such as those used for glucose detection must be developed that are capable of monitoring cell culture processes continuously and preferably noninvasively. The development of a unique noninvasive, optically based polarimetric glucose sensor is reported. The data were collected using a highly sensitive, lab-built polarimeter with digital feedback and a red laser diode source. A range of glucose concentrations was evaluated using both glucose-doped double-distilled water and a bovine serum-based medium. The serum-based medium is the nutritional environment in which the cell cultures are grown. Both media were examined across two glucose concentration ranges-a lower range of 100 mg/dl in 10-mg/dl increments and a higher range up to 600 mg/dl in 50-mg/dl increments. The linear regression in all experiments yielded standard errors of prediction of less than 8.5 mg/dl across both ranges.
Analytical Chemistry, May 28, 2020
Raman spectroscopy using aluminum nitride (AlN) optical waveguides was demonstrated for organic c... more Raman spectroscopy using aluminum nitride (AlN) optical waveguides was demonstrated for organic compound analysis. The AlN waveguide device was prepared by reactive sputtering deposition and complementary-metal-oxide semiconductor (CMOS) processes. A fundamental waveguide mode was observed over a broad visible spectrum and the waveguide evanescent wave was used to excite the Raman signals of the test analytes. The performance of the waveguide sensor was characterized by measuring the Raman spectra of the benzene derivative mixtures consisting of benzene, anisole, and toluene. The compositions and concentrations were resolved by correlating the obtained Raman spectrum with the characteristic Raman peaks associated with C-C, C-H, and C-O functional groups. With the advantages of real-time detection and enhanced Raman signal intensity, the AlN waveguides provided a sensor platform for non-destructive and on-line chemical compound monitoring.
Exploring the Clinical Utility of Raman Spectroscopy for Point-of-Care Cardiovascular Disease Biomarker Detection
Applied Spectroscopy, Jul 24, 2023
A variety of innovative point-of-care (POC) solutions using Raman systems have been explored. How... more A variety of innovative point-of-care (POC) solutions using Raman systems have been explored. However, the vast effort is in assay development, while studies of the characteristics required for Raman spectrometers to function in POC applications are lacking. In this study, we tested and compared the performance of eight commercial Raman spectrometers ranging in size from benchtop Raman microscopes to portable and handheld Raman spectrometers using paper fluidic cartridges, including their ability to detect cardiac troponin I and heart fatty acid binding protein, both of which are well-established biomarkers for evaluating cardiovascular health. Each spectrometer was evaluated in terms of excitation wavelength, laser characteristics, and ease of use to investigate POC utility. We found that the Raman spectrometers equipped with 780 and 785 nm laser sources exhibited a reduced background signal and provided higher sensitivity compared to those with 633 and 638 nm laser sources. Furthermore, the spectrometer equipped with the single acquisition line readout functionality showed improved performance when compared to the point scan spectrometers and allowed measurements to be made faster and easier. The portable and handheld spectrometers also showed similar detection sensitivity to the gold standard instrument. Lastly, we reduced the laser power for the spectrometer with single acquisition line readout capability to explore the system performance at a laser power that change the classification from a Class 3B laser device to a Class 3R device and found that it showed comparable performance. Overall, these findings show that portable Raman spectrometers have the potential to be used in POC settings with accuracy comparable to laboratory-grade instruments, are relatively low-cost, provide fast signal readout, are easy to use, and can facilitate access for underserved communities.
Optical waveguides for on-chip fluorescence measurements (Conference Presentation)
Optical Diagnostics and Sensing XIX: Toward Point-of-Care Diagnostics, 2019
Optical waveguides using a visible transparent nitride were developed to perform fluorescence mea... more Optical waveguides using a visible transparent nitride were developed to perform fluorescence measurement on a chip. Through finite difference time domain (FDTD) design, the exciting green light was guided by the micron-scale ridge waveguide, while its evanescent wave was expanded outside the waveguide surface and capable to efficiently excite the fluorescent molecules that were approaching the waveguide facets. Since the waveguide was centimeters long, it has a longer fluorescence excitation path comparing to traditional samples prepared for microscopy measurements. As result, the waveguide device can excite stronger fluorescent signals. In addition, the nitride waveguide was prepared by the complementary metal–oxide–semiconductor (CMOS) process thus enabling high volume manufacturing and reducing the cost of the device fabrication. The AlN waveguide was then integrated with a microfluidic devices to experimentally demonstrate real-time fluorescence detection. Solution samples with different dye concentrations were sequentially injected into the microfluidic chamber. By recording the emission signals, we showed that the fluorescent signals were consistently amplified as the dye concentrations increased. In addition, real-time fluorescence detection with a response time less than seconds was achieved. The developed waveguide based fluorescence measurement provides a new miniaturized platform for low cost and highly accurate point-of-care application.
Journal of biomedical optics, 2018
DNA-functionalized nanoparticles, when paired with surface-enhanced Raman spectroscopy (SERS), ca... more DNA-functionalized nanoparticles, when paired with surface-enhanced Raman spectroscopy (SERS), can rapidly detect microRNA. However, widespread use of this approach is hindered by drawbacks associated with large and expensive benchtop Raman microscopes. MicroRNA-17 (miRNA-17) has emerged as a potential epigenetic indicator of preeclampsia, a condition that occurs during pregnancy. Biomarker detection using an SERS point-of-care device could enable prompt diagnosis and prevention as early as the first trimester. Recently, strides have been made in developing portable Raman systems for field applications. An SERS assay for miRNA-17 was assessed and translated from traditional benchtop Raman microscopes to a handheld system. Three different photoactive molecules were compared as potential Raman reporter molecules: a chromophore, malachite green isothiocyanate (MGITC), a fluorophore, tetramethylrhodamine isothiocyanate, and a polarizable small molecule 5,5-dithio-bis-(2-nitrobenzoic aci...
Journal of biomedical optics, Jul 1, 2017
A point-of-care (PoC) device with the ability to detect biomarkers at low concentrations in bodil... more A point-of-care (PoC) device with the ability to detect biomarkers at low concentrations in bodily fluids would have an enormous potential for medical diagnostics outside the central laboratory. One method to monitor analytes at low concentrations is by using surface-enhanced Raman spectroscopy (SERS). In this preliminary study toward using SERS for PoC biosensing, the surface of colloidal silver (Ag) nanocubes has been modified to test the feasibility of a competitive binding SERS assay utilizing aptamers against citrulline. Specifically, Ag nanocubes were functionalized with mercaptobenzoic acid, as well as a heterobifunctional polyethylene glycol linker that forms an amide bond with the amino acid citrulline. After the functionalization, the nanocubes were characterized by zeta-potential, transmission electron microscopy images, ultraviolet/visible spectroscopy, and by SERS. The citrulline aptamers were developed and tested using backscattering interferometry. The data show that ...
Journal of biomedical optics, Aug 1, 2016
A micro- to nanochannel nanoparticle aggregating device that does not require any input energy to... more A micro- to nanochannel nanoparticle aggregating device that does not require any input energy to organize the particles to a specific location, i.e., no pumps, plugs, heat, or magnets, has been designed and used to characterize the surface-enhanced Raman spectroscopy (SERS) signal from four unique functionalized nanoparticles (gold, silver-gold nanocages, silver nanocubes, and silica-gold nanoshells). The SERS signal was assessed in terms of the peak signal strength from the four different Raman reporter functionalized nanoparticles to determine which nanoparticle had better utility in the channel to provide the most robust platform for a future biological analyte detection device. The innovation used to fabricate the micro- to nanochannel device is described; the TEM images of the nanoparticles are shown; the absorption data for the nanoparticles are given; and the spectral data for the Raman reporter, mercaptobenzoic acid (MBA), are depicted. In the micro- to nanochannel describe...
Monte Carlo modeling of spatially complex wrist tissue for the optimization of optical pulse oximeters
SPIE Proceedings, 2017
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.
SPIE Proceedings, 2014
To non-invasively measure glucose concentrations across the aqueous humor of the eye, a high-spee... more To non-invasively measure glucose concentrations across the aqueous humor of the eye, a high-speed, dual-wavelength optical polarimetric approach is proposed that addresses a key limitation of prior set-ups -system response time -while compensating for time-varying motion artifact due to corneal birefringence. This research is made up of three goals. The first goal is to design and construct a high-frequency, ferrite core Faraday rotator that can both rotate and modulate linearly polarized light in a frequency range of 30 to 75 kHz. The second goal is to implement a single ferrite core Faraday rotator into the current polarimetric approach. The third goal is to replace three air-core Faraday rotators with two ferrite core Faraday rotators for both modulation and compensation, allowing for two different signals to be measured on a single photodetector. In vitro phantom studies are performed with and without motion artifact. The sensor is shown to stabilize in ~2 msec and provide standard errors for glucose concentration of less than 13 mg/dL in the presence of motion. The results indicate that higher frequency modulation can reduce the overall system stabilization time with minimal loss of accuracy in the presence of motion artifact. Dr. Prasad Enjeti, for their support and their time. Their guidance through theory and design pointed me in the right directions. Mr. Erwin Thomas III and Dr. Bilal Malik both guided me in new and interesting directions as well. Thanks also go to my friends, including but not limited to Casey Pirnstill, Tony Akl, Zhen Fang, Brian Cummins, Haley Marks, Javier Garza, and Andrea Locke. They have all been helpful during these past few years. Finally, I'd like to acknowledge my family, including but not limited to my mom, who never gave up on my education, my sister, who gave me the best advice and support, my brother, who has always supported me in whatever I do, and my girlfriend, who supported me when I needed it the most.
Nanoparticle based biosensor for the detection of BSE in foods
The use of surface enhanced Raman spectroscopy (SERS) in a competitive affinity binding assay for the detection of prions
Annual International Conference of the IEEE Engineering in Medicine and Biology Society, 2003
The recent reports of spread of transmissible spongiform encephalopathies such as bovine spongifo... more The recent reports of spread of transmissible spongiform encephalopathies such as bovine spongiform encephalopathy to humans has led to the need to develop rapid and sensitive methods* for the detection for the infectious agent of these diseases, prions, in a variety of biological samples. A novel surface enhanced Raman spectroscopy (SERS) based method has been developed for the detection of
In vitro detection of beta amyloid exploiting surface enhanced Raman scattering (SERS) using a nanofluidic biosensor
SPIE Proceedings, 2008
... In vitro detection of beta amyloid exploiting surface enhanced Raman scattering (SERS) using ... more ... In vitro detection of beta amyloid exploiting surface enhanced Raman scattering (SERS) using a nanofluidic biosensor (Proceedings Paper). ... Alzheimer's disease (AD), a neurodegenerative disease and the most common cause of dementia, affects 4.5 million people ...
A surface enhanced Raman spectroscopy platform based on nanoshells for detection of β-amyloid
SPIE Proceedings, 2008
A major limitation of many surfaced enhanced Raman spectroscopy (SERS) approaches is the dependen... more A major limitation of many surfaced enhanced Raman spectroscopy (SERS) approaches is the dependence of the Raman enhancement on the local nanostructure. While these local "hot spots" may provide areas of extremely strong enhancement, which make trace analyte detection possible, they also make quantitative measurements problematic. Gold nanoshells however, with the ratio of the radius of their silica core to
Functionalized nanoparticles for measurement of biomarkers using a SERS nanochannel platform
SPIE Proceedings, 2010
The overall goal of this research is to develop a new point-of-care system for early detection an... more The overall goal of this research is to develop a new point-of-care system for early detection and characterization of cardiac markers to aid in diagnosis of acute coronary syndrome. The envisioned final technology platform incorporates functionalized gold colloidal nanoparticles trapped at the entrance to a nanofluidic device providing a robust means for analyte detection at trace levels using surface enhanced
Journal of Biomedical Optics, 2006
Current research has revealed the importance of a class of cell surface proteins called integrins... more Current research has revealed the importance of a class of cell surface proteins called integrins in various vital physiological functions such as blood clotting, regulation of blood pressure, tissue blood flow, and vascular remodeling. The key to integrin functionality is its ability to mediate force transmission by interacting with the extracellular matrix and cytoskeleton. In addition, they play a role in signal transduction via their connection with the proteins in focal adhesion ͑FA͒ points. To understand the complex mechanism of cell-cell and cell-extracellular matrix ͑ECM͒ adhesion that is responsible for these diverse biochemical interactions, it is necessary to identify the integrins on cells and monitor their interaction with various ligands. To this end, for the first time, we employ surface-enhanced Raman spectroscopy ͑SERS͒ to detect integrins. The results show the capability using SERS to detect the integrins to the nanomolar concentration regime and to distinguish between two different kinds of integrins, ␣V3 and ␣51, that are present in vascular smooth muscle cells ͑VSMCs͒. It is anticipated that the SERS approach will potentially help elucidate the mechanism of integrin-ligand interactions in a variety of phenomena of physiological importance.
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.