KEYWORDS: Biological detection systems, Nanosensors, Cell phones, Error analysis, Light sources and illumination, Video processing, Medical diagnostics, Opacity, Data processing, Video
Urinalysis dipsticks were designed to revolutionize urine-based medical diagnosis. They are cheap, extremely portable, and have multiple assays patterned on a single platform. They were also meant to be incredibly easy to use. Unfortunately, there are many aspects in both the preparation and the analysis of the dipsticks that are plagued by user error. This high error is one reason that dipsticks have failed to flourish in both the at-home market and in low-resource settings. Sources of error include: inaccurate volume deposition, varying lighting conditions, inconsistent timing measurements, and misinterpreted color comparisons. We introduce a novel manifold and companion software for dipstick urinalysis that eliminates the aforementioned error sources. A micro-volume slipping manifold ensures precise sample delivery, an opaque acrylic box guarantees consistent lighting conditions, a simple sticker-based timing mechanism maintains accurate timing, and custom software that processes video data captured by a mobile phone ensures proper color comparisons. We show that the results obtained with the proposed device are as accurate and consistent as a properly executed dip-and-wipe method, the industry gold-standard, suggesting the potential for this strategy to enable confident urinalysis testing. Furthermore, the proposed all-acrylic slipping manifold is reusable and low in cost, making it a potential solution for at-home users and low-resource settings.
Optical coherence tomography (OCT) and blue light cystoscopy (BLC) have shown significant potential as complementary technologies to traditional white light cystoscopy (WLC) for early bladder cancer detection. Three-dimensional (3D) organ-mimicking phantoms provide realistic imaging environments for testing new technology designs, the diagnostic potential of systems, and novel image processing algorithms prior to validation in real tissue. Importantly, the phantom should mimic features of healthy and diseased tissue as they appear under WLC, BLC, and OCT, which are sensitive to tissue color and structure, fluorescent contrast, and optical scattering of subsurface layers, respectively. We present a phantom posing the hollow shape of the bladder and fabricated using a combination of 3D-printing and spray-coating with Dragon Skin (DS) (Smooth-On Inc.), a highly elastic polymer to mimic the layered structure of the bladder. Optical scattering of DS was tuned by addition of titanium dioxide, resulting in scattering coefficients sufficient to cover the human bladder range (0.49 to 2.0 mm^-1). Mucosal vasculature and tissue coloration were mimicked with elastic cord and red dye, respectively. Urethral access was provided through a small hole excised from the base of the phantom. Inserted features of bladder pathology included altered tissue color (WLC), fluorescence emission (BLC), and variations in layered structure (OCT). The phantom surface and underlying material were assessed on the basis of elasticity, optical scattering, layer thicknesses, and qualitative image appearance. WLC, BLC, and OCT images of normal and cancerous features in the phantom qualitatively matched corresponding images from human bladders.
Optical coherence tomography (OCT) has become a standard tool in ophthalmology clinics for diagnosing many retinal diseases. Nonetheless, the technical and clinical communities still lack a standardized phantom that could aid in evaluating and normalizing the many protocols and systems used for diagnosis. Existing retinal phantoms are able to mimic the thickness and scattering properties of the retinal layers but are unable to model the morphology of the foveal pit, particularly the tapering of the retinal layers. This work demonstrates a new fabrication procedure that is capable of reliably and consistently replicating the shape and tapered appearance of the retinal layers near the foveal pit using a combination of spin-coating and replica molding. We characterize the effects of using different mold sizes which enable us to achieve a range of pit dimensions. We also present a modified procedure to replicate two diseased states of the retinal tissue, such as retinal detachment and dry aged-related macular degeneration. The ability to create an anatomically correct foveal pit for healthy and disease-mimicking phantoms will allow for a new standard better suited for intra- and inter-system evaluation and for improved comparison of retinal segmentation algorithms.
Optical Coherence Tomography (OCT) has become a standard tool for diagnosing retinal disease in many ophthalmology clinics. Nonetheless, the technical and clinical research communities still lack a standardized phantom that could aid in evaluating and normalizing the various scan protocols and OCT machines employed at different institutions. Existing retinal phantoms designed for OCT imaging mimic some important features of the retina, such as the thickness and scattering properties of its many layers. However, the morphology of the foveal pit and the visible tapering of the retinal layers underlying the surface surrounding the pit remains a challenge to replicate in current phantoms. Recent attempts at creating a realistic foveal pit include molding, ablation and laser etching but have not proved sufficient to replicate this particular anatomical feature. In this work, we demonstrate a new fabrication procedure that is capable of replicating the tapered appearance of the retinal layers near the foveal pit using a combination of spin-coating and replica molding. The ability to create an anatomically correct foveal pit will allow for a new phantom better suited for intra- and inter-system evaluation and for improved testing of retinal segmentation algorithms.
Speckle noise is one of the dominant factors that degrade image quality in optical coherence tomography (OCT). Here, we propose a new strategy, interleaved OCT (iOCT), for spatial compounding and angular compounding. We demonstrate the efficiency of compounding with iOCT to restrain speckle noise without compromising imaging speed in phantoms and tissue samples.
We present a novel strategy for label-free detection of glucose based on CdSe/ZnS core/shell quantum dots (QDs).
We exploit the concentration-dependent, narrowband absorption of the hexokinase-glucose 6-phosphate
dehydrogenase enzymatic assay to selectively filter a 365-nm excitation source, leading to a proportional decrease in
the photoluminescence intensity of the QDs. The visible wavelength emission of the QDs enables quantitative
readout using standard visible detectors (e.g., CCD). Experimental results show highly linear QD
photoluminescence over the clinically relevant glucose concentration range of 1-25mM, in excellent agreement with
detection methods demonstrated by others. The method has a demonstrated limit of detection of 3.5μM, also on par
with the best proposed methods. A significant advantage of our strategy is the complete elimination of QDs as a
consumable. In contrast with other methods of QD-based measurement of glucose, our system does not require the
glucose solution to be mixed with the QDs, thereby decreasing its overall cost and making it an ideal strategy for
point-of-care detection of glucose in low-resource areas. Furthermore, readout can be accomplished with low-cost,
portable detectors such as cellular phones, eliminating the need for expensive and bulky spectrophotometers to
output quantitative information. The general strategy we present is useful for other biosensing applications
involving chemistries with unique absorption peaks falling within the excitation band of available QDs.
Optical coherence tomography (OCT) has shown potential as a complementary modality to white light cystoscopy (WLC), the gold standard for imaging bladder cancer. OCT can visualize sub-surface details of the bladder wall, which enables it to stage cancers and detect tumors that are otherwise invisible to WLC. Currently, OCT systems have too slow a speed and too small a field of view for comprehensive bladder imaging, which limits its clinical utility. Validation and feasibility testing of technological refinements aimed to provide faster imaging and wider fields of view necessitates a realistic bladder phantom. We present a novel process to fabricate the first such phantom that mimics both the optical and morphological properties of layers of the healthy and pathologic bladder wall as they characteristically appear with OCT. The healthy regions of the silicone-based phantom comprises three layers: the urothelium, lamina propria and muscularis propria, each containing an appropriate concentration of titanium dioxide to mimic its distinct scattering properties. As well, the layers each possess a unique surface appearance imposed by a textured mold. Within this phantom, pathologic tissue-mimicking regions are created by thickening specific layers or creating inclusions that disrupt the layered appearance of the bladder wall, as is characteristic of bladder carcinomas. This phantom can help to evaluate the efficacy of new OCT systems and software for tumor localization. Moreover, the procedure we have developed is highly generalizable for the creation of OCT-relevant, multi-layer phantoms for tissues that incorporate diseased states characterized by the loss of layered structures.
We describe a combination of fabrication techniques and a general process to construct a three-dimensional (3-D) phantom that mimics the size, macroscale structure, microscale surface topology, subsurface microstructure, optical properties, and functional characteristics of a cancerous bladder. The phantom also includes features that are recognizable in white light (i.e., the visual appearance of blood vessels), making it suitable to emulate the bladder for emerging white light+optical coherence tomography (OCT) cystoscopies and other endoscopic procedures of large, irregularly shaped organs. The fabrication process has broad applicability and can be generalized to OCT phantoms for other tissue types or phantoms for other imaging modalities. To this end, we also enumerate the nuances of applying known fabrication techniques (e.g., spin coating) to contexts (e.g., nonplanar, 3-D shapes) that are essential to establish their generalizability and limitations. We anticipate that this phantom will be immediately useful to evaluate innovative OCT systems and software being developed for longitudinal bladder surveillance and early cancer detection.
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