Publications by authors named "Alex C-T Ko"

Acute respiratory tract infections (ARTIs) are caused by sporadic or pandemic outbreaks of viral or bacterial pathogens, and continue to be a considerable socioeconomic burden for both developing and industrialized countries alike. Diagnostic methods and technologies serving as the cornerstone for disease management, epidemiological tracking, and public health interventions are evolving continuously to keep up with the demand for higher sensitivity, specificity and analytical throughput. Microfluidics is becoming a key technology in these developments as it allows for integrating, miniaturizing and automating bioanalytical assays at an unprecedented scale, reducing sample and reagent consumption and improving diagnostic performance in terms of sensitivity, throughput and response time.

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Objectives: The COVID-19 pandemic caused a global shortage of nasopharyngeal (NP) swabs, required for RT-PCR testing. Canadian manufacturers were contacted to share NP swab innovations. The primary objective was to determine whether novel NP test swabs were comparable to commercially available swabs regarding user characteristics, ability to collect a specimen, and diagnostic performance using RT-PCR testing.

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Chronic kidney disease (CKD) typically evolves over many years in a latent period without clinical signs, posing key challenges to detection at relatively early stages of the disease. Accurate and timely diagnosis of CKD enable effective management of the disease and may prevent further progression. However, long turn-around times of current testing methods combined with their relatively high cost due to the need for established laboratory infrastructure, specialized instrumentation and trained personnel are drawbacks for efficient assessment and monitoring of CKD, especially in underserved and resource-poor locations.

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Structural proteins like collagen and elastin are major constituents of the extracellular matrix (ECM). ECM degradation and remodeling in diseases significantly impact the microorganization of these structural proteins. Therefore, tracking the changes of collagen and elastin fiber morphological features within ECM impacted by disease progression could provide valuable insight into pathological processes such as tissue fibrosis and atherosclerosis.

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Wound management is a challenging and costly problem that is growing in importance as people are living longer. Instrumental methods are increasingly being relied upon to provide objective measures of wound assessment to help guide management. Technologies that employ near-infrared (NIR) light form a prominent contingent among the existing and emerging technologies.

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Surface modified mesoporous silica nanoparticles (MSNs) with reduced toxicity were prepared for light and pH dual triggerable drug delivery system. Both 413 nm light and acidic environment can activate the drug release process, improving the pharmacological action. By applying rhodamine B (RhB) as a model drug, the accumulative RhB release is as high as 95% in pH 5.

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Quantification of atherosclerosis has been a challenging task owing to its complex pathology. In this study, we validated a quantitative approach for assessing atherosclerosis progression in a rabbit model using a numerical matrix, optical index for plaque burden, derived directly from the nonlinear optical microscopic images captured on the atherosclerosis-affected blood vessel. A positive correlation between this optical index and the severity of atherosclerotic lesions, represented by the age of the rabbits, was established based on data collected from 21 myocardial infarction-prone Watanabe heritable hyperlipidemic rabbits with age ranging between new-born and 27 months old.

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In this work, we synthesized a pH sensitive poly(ethylene glycol)-doxorubicin (PEG-DOX) on single-wall carbon nanotubes (SWNTs). Using multimodal nonlinear optical imaging microscopy, we found that low power (1 mW cm) near-infrared radiation can initiate prodrug burst release from the carbon nanotubes in seconds. The successful SWNTs capping with PEG-DOX (denoted PEG-DOX@SWNT) was determined by transmission electron microscopy and FTIR results.

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In this study we present an image analysis methodology capable of quantifying morphological changes in tissue collagen fibril organization caused by pathological conditions. Texture analysis based on first-order statistics (FOS) and second-order statistics such as gray level co-occurrence matrix (GLCM) was explored to extract second-harmonic generation (SHG) image features that are associated with the structural and biochemical changes of tissue collagen networks. Based on these extracted quantitative parameters, multi-group classification of SHG images was performed.

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Pathological understanding of arterial diseases is mainly attributable to histological observations based on conventional tissue staining protocols. The emerging development of nonlinear optical microscopy (NLOM), particularly in second-harmonic generation, two-photon excited fluorescence and coherent Raman scattering, provides a new venue to visualize pathological changes in the extracellular matrix caused by atherosclerosis progression. These techniques in general require minimal tissue preparation and offer rapid three-dimensional imaging.

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The composition and structure of atherosclerotic lesions can be directly related to the risk they pose to the patient. Multimodal nonlinear optical (NLO) microscopy provides a powerful means to visualize the major extracellular components of the plaque that critically determine its structure. Textural features extracted from NLO images were investigated for their utility in providing quantitative descriptors of structural and compositional changes associated with plaque development.

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A femtosecond CARS-based nonlinear optical microscope was used to simultaneously image extracellular structural proteins and lipid-rich structures within intact aortic tissue obtained from myocardial infarction-prone Watanabe heritable hyperlipidemic rabbits (WHHLMI). Clear differences in the NLO microscopic images were observed between healthy arterial tissue and regions dominated by atherosclerotic lesions. In the current ex-vivo study, we present a single parameter based on intensity changes derived from multi-channel NLO image to classify plaque burden within the vessel.

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Label-free imaging of bulk arterial tissue is demonstrated using a multimodal nonlinear optical microscope based on a photonic crystal fiber and a single femtosecond oscillator operating at 800 nm. Colocalized imaging of extracellular elastin fibers, fibrillar collagen, and lipid-rich structures within aortic tissue obtained from atherosclerosis-prone myocardial infarction-prone Watanabe heritable hyperlipidemic (WHHLMI) rabbits is demonstrated through two-photon excited fluorescence, second harmonic generation, and coherent anti-Stokes Raman scattering, respectively. These images are shown to differentiate healthy arterial wall, early atherosclerotic lesions, and advanced plaques.

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A new fibre-optic coupled polarization-resolved Raman spectroscopic system was developed for simultaneous collection of orthogonally polarized Raman spectra in a single measurement. An application of detecting incipient dental caries based on changes observed in Raman polarization anisotropy was also demonstrated using the developed fibre-optic Raman spectroscopic system. The predicted reduction of polarization anisotropy in the Raman spectra of caries lesions was observed and the results were consistent with those reported previously with Raman microspectroscopy.

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The demineralization of enamel that is associated with early caries formation affects the optical properties of the enamel. Polarized Raman spectroscopy and optical coherence tomography have been used to detect these changes and potentially offer a means to detect and monitor early caries development. The total optical attenuation coefficient as measured by optical coherence tomography and the polarization anisotropy of the Raman peak arising from the symmetric nu(1) vibration of PO4(3-) at approximately 959 cm(-1) have been demonstrated as being sensitive markers of early caries.

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Identification and quantification of molecular species are central applications of molecular spectroscopy. In complex multicomponent systems like tissue samples, linear parametric models are often used to estimate the relative concentrations of the biochemical components of the sample. In situations where not all of the components of the sample are known or modeled, such parametric models can suffer from omitted variable bias and result in skewed estimates of component concentrations.

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A new technique based on polarized Raman spectroscopy is demonstrated for detecting early dental caries on extracted human teeth. Sound tooth enamel exhibited strong Raman polarization anisotropy whereas early caries consistently showed a lower degree of Raman polarization anisotropy. In particular, for sound enamel, the Raman peak arising from the symmetric nu1 vibration of PO(4) (3-) at 959 cm(-1) is strongly polarized.

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Early dental caries detection will facilitate implementation of nonsurgical methods for arresting caries progression and promoting tooth remineralization. We present a method that combines optical coherence tomography (OCT) and Raman spectroscopy to provide morphological information and biochemical specificity for detecting and characterizing incipient carious lesions found in extracted human teeth. OCT imaging of tooth samples demonstrated increased light backscattering intensity at sites of carious lesions as compared to the sound enamel.

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