Early diagnosis and accurate assessment of tumor development facilitate early bladder cancer resection and initiation of drug therapy. This study enabled an early, accurate, label-free, noninvasive diagnosis of bladder tumors by analyzing nano-biomarkers in a single drop of urine through surface-enhanced Raman spectroscopy (SERS). In a standard N-butyl-N-4-hydroxybutyl nitrosamine-induced rat model of bladder cancer, cancer stage and polyp tumor development were monitored using a small endoscope with a diameter of 1.2 mm in a minimally invasive manner without the need to kill the rats. Samples were divided into cancer-free, early-stage, and polyp-form cancer. Training data were classified according to micro-cystoscopic 5-aminolevulinic acid fluorescence diagnosis, and specimens were postmortem verified through histopathological analysis. A drop of urine from each sample group was placed on an Au-coated zinc oxide nanoporous chip to filter nano-biomaterials and selectively enhance the Raman signals of nanoscale analytes via SERS. Principal component analysis was used to reduce the dimensionality of the collected Raman spectra, and partial least squares discriminant analysis was used to find diagnostic clusters based on the labeled samples. The combination of SERS and machine learning achieved an accuracy ≥99.6% in diagnosing both early- and polyp-stage bladder tumors. With an area under the receiver operating characteristic curve greater than 0.996, the accuracy of the diagnosis in the rat model suggests that SERS-based diagnostic methods are promising when coupled with machine learning. Low-cost, label-free, and noninvasive surface-enhanced Raman spectra are ideal for developing clinically relevant point-of-care diagnostic techniques.

Laser speckle contrast imaging (LSCI) is a powerful visualization tool for quantifying blood flow in tissues, providing simplicity of configuration, ease of use, and intuitive results. With recent advancements, smartphone and camera technologies are suitable for the development of smartphone-based LSCI applications for point-of-care (POC) diagnosis. A smartphone-based portable LSCI endoscope system was validated for POC diagnosis of vascular disorders. The endoscope consisted of compact LED and laser illumination, imaging optics, and a flexible fiberscope assembled in a 3D-printed hand-held cartridge for access to body cavities and organs. A smartphone’s rear camera was mounted thereto, enabling endoscopy, LSCI image acquisition, and processing. Blood flow imaging was calibrated in a perfused tissue phantom consisting of a microparticle solution pumped at known rates through tissue-mimicking gel and validated in a live rat model of BBN-induced bladder cancer. Raw LSCI images successfully visualized phantom flow: speckle flow index showed linearity with the pump flow rate. In the rat model, healthy and cancerous bladders were distinguishable in structure and vasculature. The smartphone-based low-cost portable mobile endoscope for monitoring blood flow and perfusion shows promise for preclinical applications and may be suitable for primary diagnosis at home or as a cost-effective POC testing assay.

Background: Endoscopes are widely used for visualizing the respiratory tract, urinary tract, uterus, and gastrointestinal tracts. Despite high demand, people in underdeveloped and developing countries cannot obtain proper access to endoscopy. Moreover, commercially available endoscopes are mostly nonarticulable as well as not actively controlled, limiting their use. Articulating endoscopes are required for some diagnosis procedures, due to their ability to image wide areas of internal organs. Furthermore, actively controlled articulating endoscopes are less likely to harm the lumen than rigid endoscopes because they can avoid contact with endothelial tissues. Objective: The study aimed to demonstrate the feasibility and acceptability of smartphone-based wide-field articulable endoscope system for minimally invasive clinical applications in developing and less developed countries. Methods: A thin articulable endoscope system that can be attached to and actively controlled by a smartphone was designed and constructed. The system consists of a flexible endoscopic probe with a continuum mechanism, 4 motor modules for articulation, a microprocessor for controlling the motor with a smartphone, and a homebuilt app for streaming, capturing, adjusting images and video, and controlling the motor module with a joystick-like user interface. The smartphone and motor module are connected via an integrated C-type On-The-Go (OTG) USB hub. Results: We tested the device in several human-organ phantoms to evaluate the usability and utility of the smartphone-based articulating endoscope system. The resolution (960 × 720 pixels) of the device was found to be acceptable for medical diagnosis. The maximum bending angle of 110° was designed. The distance from the base of the articulating module to the tip of the endoscope was 45 mm. The angle of the virtual arc was 40.0°, for a curvature of 0.013. The finest articulation resolution was 8.9°. The articulating module succeeded in imaging all 8 octants of a spherical target, as well as all 4 quadrants of the indices marked in human phantoms. Conclusions: The portable wide-field endoscope was successfully controlled using a smartphone, yielding clear images with a resolution of 960 × 720 pixels at realistic focal distances. Actively and precisely controlled articulating movements have resulted in minimally invasive monitoring in the narrow space of internal organs providing a wide-area view. We found our smartphone-based active articulated endoscope to be suitable for point-of-care applications in developing and less developed countries.

Background: Currently, high-speed digital imaging (HSDI), especially endoscopic HSDI, is routinely used for the diagnosis of vocal cord disorders. However, endoscopic HSDI devices are usually large and costly, which limits access to patients in underdeveloped countries and in regions with inadequate medical infrastructure. Modern smartphones have sufficient functionality to process the complex calculations that are required for processing high-resolution images and videos with a high frame rate. Recently, several attempts have been made to integrate medical endoscopes with smartphones to make them more accessible to people in underdeveloped countries. Objective: This study aims to develop a smartphone adaptor for endoscopes, which enables smartphone-based vocal cord imaging, to demonstrate the feasibility of performing high-speed vocal cord imaging via the high-speed imaging functions of a high-performance smartphone camera, and to determine the acceptability of the smartphone-based high-speed vocal cord imaging system for clinical applications in developing countries. Methods: A customized smartphone adaptor optical relay was designed for clinical endoscopy using selective laser melting–based 3D printing. A standard laryngoscope was attached to the smartphone adaptor to acquire high-speed vocal cord endoscopic images. Only existing basic functions of the smartphone camera were used for HSDI of the vocal cords. Extracted still frames were observed for qualitative glottal volume and shape. For image processing, segmented glottal and vocal cord areas were calculated from whole HSDI frames to characterize the amplitude of the vibrations on each side of the glottis, including the frequency, edge length, glottal areas, base cord, and lateral phase differences over the acquisition time. The device was incorporated into a preclinical videokymography diagnosis routine to compare functionality. Results: Smartphone-based HSDI with the smartphone-endoscope adaptor could achieve 940 frames per second and a resolution of 1280 by 720 frames, which corresponds to the detection of 3 to 8 frames per vocal cycle at double the spatial resolution of existing devices. The device was used to image the vocal cords of 4 volunteers: 1 healthy individual and 3 patients with vocal cord paralysis, chronic laryngitis, or vocal cord polyps. The resultant image stacks were sufficient for most diagnostic purposes. The cost of the device including the smartphone was lower than that of existing HSDI devices. The image processing and analytics demonstrated the successful calculation of relevant diagnostic variables from the acquired images. Patients with vocal pathologies were easily differentiable in the quantitative data. Conclusions: A smartphone-based HSDI endoscope system can function as a point-of-care clinical diagnostic device. The resulting analysis is of higher quality than that accessible by videostroboscopy and promises comparable quality and greater accessibility than HSDI. In particular, this system is suitable for use as an accessible diagnostic tool in underdeveloped areas with inadequate medical service infrastructure.

We present a fiber-optic sensor based on the principles of a Fabry–Perot interferometer (FPI), which promptly, sensitively, and precisely detects blood clot formation. This sensor has two types of sensor tips; the first was crafted by splicing a tapered fiber into a single-mode fiber (SMF), where fine-tuning was achieved by adjusting the tapered diameter and length. The second type is an ultra-compact blood FPI situated on the core of a single-mode fiber. The sensor performance was evaluated via clot-formation-indicating spectrum shifts induced by the varied quantities of a thrombin reagent introduced into the blood. The most remarkable spectral sensitivity of the micro-tip fiber type was approximately 7 nm/μL, with a power sensitivity of 4.1 dB/μL, obtained with a taper fiber diameter and length of 55 and 300 μm, respectively. For the SMF type, spectral sensitivity was observed to be 8.7 nm/μL, with an optical power sensitivity of 0.4 dB/μL. This pioneering fiber-optic thrombosis sensor has the potential for in situ applications, healthcare, medical monitoring, harsh environments, and chemical and biological sensing. The study underscores the scope of optical technology in thrombus detection, establishing a platform for future medical research and application.

Complex clinical procedures and small-animal research procedures can benefit from dual-site imaging provided by multiple endoscopic devices. Here, an endoscopic system is proposed which enables multiple fluorescence microendoscopes to be spectrally multiplexed on a single microscope base, enabling light sources and optical relays to be shared between endoscopes. The presented system is characterized for resolution using USAF-1951 resolution test charts and for modulation transfer function using the slanted edge method. Imaging is demonstrated both directly and with microendoscopes attached. Imaging of phantoms was demonstrated by targeting USAF charts and fiber tissues dyed for FITC and Texas Red fluorescence. Afterwards, simultaneous liver and kidney imaging was demonstrated in mice expressing mitochondrial Dendra2 and injected with Texas Red-dextran. The results indicate that the system achieves high channel isolation and submicron and subcellular resolution, with resolution limited by the endoscopic probe and by physiological movement during endoscopic imaging. Multi-channel microendoscopy provides a potentially low-cost means of simultaneous multiple endoscopic imaging during biological experiments, resulting in reduced animal harm and potentially increasing insight into temporal connections between connected biological systems.