Development of a Quantitative Digital Urinalysis Tool for Detection of Nitrite, Protein, Creatinine, and pH.

This paper presents a cost-effective, quantitative, point-of-care solution for urinalysis screening, specifically targeting nitrite, protein, creatinine, and pH in urine samples. Detecting nitrite is crucial for the early identification of urinary tract infections (UTIs), while regularly measuring urinary protein-to-creatinine (UPC) ratios aids in managing kidney health. To address these needs, we developed a portable, transmission-based colorimeter using readily available components, controllable via a smartphone application through Bluetooth. Multiple colorimetric detection strategies for each analyte were identified and tested for sensitivity, specificity, and stability in a salt buffer, artificial urine, and human urine. The colorimeter successfully detected all analytes within their clinically relevant ranges: nitrite (6.25-200 µM), protein (2-1024 mg/dL), creatinine (2-1024 mg/dL), and pH (5.0-8.0). The introduction of quantitative protein and creatinine detection, and a calculated urinary protein-to-creatinine (UPC) ratio at the point-of-care, represents a significant advancement, allowing patients with proteinuria to monitor their condition without frequent lab visits. Furthermore, the colorimeter provides versatile data storage options, facilitating local storage on mobile devices or in the cloud. The paper further details the setup of the colorimeter's secure connection to a cloud-based environment, and the visualization of time-series analyte measurements in a web-based dashboard.

Toward a Quantitative Colorimeter for Point-of-Care Nitrite Detection.

This paper reports on a low-cost, quantitative, point-of-care solution for the early detection of nitrite, a common biomarker for urinary tract infections (UTIs). In a healthy individual, nitrite is not found in the urine. However, a subject with a suspected UTI will produce nitrite in their urine since the bacteria present will convert nitrate into nitrite. Traditionally, nitrite is monitored by urinary dipsticks that are either read by eye or using a reflectance spectrophotometer. Both methods provide a semiquantitative positive or negative result at best. In this paper, we described a novel, affordable, portable transmission-based colorimeter for the quantitative measurement of nitrite. A unique permutation of the Griess reaction was optimized for the clinical detection of nitrite in urine and is reported. By using nitrite spiked in a salt buffer, artificial, and human urine samples, the performance of the colorimeter was evaluated against dipsticks read using two commercial dipstick analyzers, Urisys 1100 (Roche Diagnostics) and Clinitek Status+ (Siemens Medical Solutions). The colorimeter was able to detect the clinically relevant range of nitrite from 0.78 to 200 µM in a salt buffer. The detection limit in artificial urine was determined as 1.6 µM, which is ∼16× more sensitive than commercial dipstick reflectance analyzers, enabling the possibility for earlier detection of urinary infections. The colorimeter is assembled using off-the-shelf components (<$80) and controlled by a smartphone application via low-energy bluetooth. It has a built-in color correction algorithm and is designed to enable for a turbidity correction in samples containing bacteria or other cellular debris as well. The mobile application can display the nitrite concentration for a single sample or display the results over a period of time. Tracking urinalysis results longitudinally can help identify trends such as increases in nitrite concentrations over an individual's baseline and identify possible infections earlier. While the detection of nitrite was showcased here, this portable analyzer can be expanded to other colorimetric-based chemistries to detect a panel of biomarkers, which can improve the overall sensitivity and specificity of the desired assay.

A mask R-CNN based automatic assessment system for nail psoriasis severity.

Nail psoriasis significantly impacts the quality of life in patients with psoriasis, which affects approximately 2-3% of the population worldwide. Disease severity measures are essential in guiding treatment and evaluation of therapeutic efficacy. However, due to subsidy, convenience and low costs of health care in Taiwan, doctor usually needs to manage nearly hundreds of patients in single outpatient clinic, leading to difficulty in performing complex assessment tools. For instance, Nail Psoriasis Severity index (NAPSI) is used by dermatologists to measure the severity of nail psoriasis in clinical trials, but its calculation is quite time-consuming, which hampers its application in daily clinical practice. Therefore, we developed a simple, fast and automatic system for the assessment of nail psoriasis severity by constructing a standard photography capturing system combined with utilizing one of the deep learning architectures, mask R-CNN. This system not only assist doctors in capturing signs of disease and normal skin, but also able to extract features without pre-processing of image data. Expectantly, the system could help dermatologists make accurate diagnosis, assessment as well as provide precise treatment decision more efficiently.

A Graphene Oxide-interfaced Microfluidics System for Isolating and Capturing Circulating Tumor Cells and Microemboli.

Circulating tumor cells (CTCs) and circulating tumor microemboli (CTM) are rare cell species present in peripheral blood and appear in circulatory system during cancer metastasis. As phenotype of single or aggregated CTCs can be different and may present different levels of potential aggressiveness, detecting and capturing both of them are crucial for preventing recurrence as well as achieving early-stage diagnosis. This research presents a microfluidics system aiming at isolating and highly sensitive capturing of CTCs and CTMs. A serpentine channel and a series of bifurcating micro-channels were use to separate CTCs and CTMs from other blood cells. A graphene oxide interface was patterned on glass slide to facilitate antibodies conjugation via click chemistry for capturing CTCs and CTMs, thus achieving multiplex detection in a high specificity and bio-compatibility manner.

Generation of High-resolution Lung Computed Tomography Images using Generative Adversarial Networks.

To deal with the limiting data in training for new deep learning modules, we purpose a method to generate high-resolution medical images by implementing generative adversarial networks (GAN) models. Firstly, the boundary equilibrium generative adversarial networks model was used to generate the whole lung computed tomography images. Image inpainting was then integrated to generate the delicate details of the lung part by dividing into a coarse network and a refinement network to inpaint more completed and intricate details. With this method, we aim to increase the amount of high-resolution medical images for future applications in deep learning.

Microfluidics and Nanomaterial-based Technologies for Circulating Tumor Cell Isolation and Detection.

Cancer has been one of the leading causes of death globally, with metastases and recurrences contributing to this result. The detection of circulating tumor cells (CTCs), which have been implicated as a major population of cells that is responsible for seeding and migration of tumor sites, could contribute to early detection of metastasis and recurrences, consequently increasing the chances of cure. This review article focuses on the current progress in microfluidics technology in CTCs diagnostics, extending to the use of nanomaterials and surface modification techniques for diagnostic applications, with an emphasis on the importance of integrating microchannels, nanomaterials, and surface modification techniques in the isolating and detecting of CTCs.

Graphene Oxide-Based Biosensors for Liquid Biopsies in Cancer Diagnosis.

Liquid biopsies use blood or urine as test samples, which are able to be continuously collected in a non-invasive manner. The analysis of cancer-related biomarkers such as circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), microRNA, and exosomes provides important information in early cancer diagnosis, tumor metastasis detection, and postoperative recurrence monitoring assist with clinical diagnosis. However, low concentrations of some tumor markers, such as CTCs, ctDNA, and microRNA, in the blood limit its applications in clinical detection and analysis. Nanomaterials based on graphene oxide have good physicochemical properties and are now widely used in biomedical detection technologies. These materials have properties including good hydrophilicity, mechanical flexibility, electrical conductivity, biocompatibility, and optical performance. Moreover, utilizing graphene oxide as a biosensor interface has effectively improved the sensitivity and specificity of biosensors for cancer detection. In this review, we discuss various cancer detection technologies regarding graphene oxide and discuss the prospects and challenges of this technology.

The Development of Controllable Magnetic Driven Microphysiological System.

Current research has enabled the use of microphysiological systems and creation of models for alveolar and pulmonary diseases. However, bottlenecks remain in terms of medium- and long-term regulation of cell cultures and their functions in microchannel systems, as well as in the enhancement of in vitro representation of alveolar models and reference values of the data. Currently used systems also require on-chip manufacturing of complex units, such as pumps, tubes, and other cumbersome structures for maintaining cells in culture. In addition, system simplification and minimization of all external and human factors major challenges facing the establishment of in vitro alveolar models. In this study, a magnetically driven dynamic alveolus cell-culture system has been developed to use controlled magnetic force to drive a magnetic film on the chip, thereby directing the fluid within it to produce a circulating flow. The system has been confirmed to be conducive with regard to facilitating uniform attachment of human alveolar epithelial cells and long-term culture. The cell structure has been recapitulated, and differentiation functions have been maintained. Subsequently, reactions between silica nanoparticles and human alveolar epithelial cells have been used to validate the effects and advantages of the proposed dynamic chip-based system compared to a static environment. The innovative concept of use of a magnetic drive has been successfully employed in this study to create a simple and controllable yet dynamic alveolus cell-culture system to realize its functions and advantages with regard to in vitro tissue construction.

Graphene- and Graphene Oxide-Based Nanocomposite Platforms for Electrochemical Biosensing Applications.

Graphene and its derivatives such as graphene oxide (GO) and reduced GO (rGO) offer excellent electrical, mechanical and electrochemical properties. Further, due to the presence of high surface area, and a rich oxygen and defect framework, they are able to form nanocomposites with metal/semiconductor nanoparticles, metal oxides, quantum dots and polymers. Such nanocomposites are becoming increasingly useful as electrochemical biosensing platforms. In this review, we present a brief introduction on the aforementioned graphene derivatives, and discuss their synthetic strategies and structure-property relationships important for biosensing. We then highlight different nanocomposite platforms that have been developed for electrochemical biosensing, introducing enzymatic biosensors, followed by non-enzymatic biosensors and immunosensors. Additionally, we briefly discuss their role in the emerging field of biomedical cell capture. Finally, a brief outlook on these topics is presented.

Enhanced Osteogenic Differentiation of Stem Cells on Phase-Engineered Graphene Oxide.

Graphene oxide (GO) has attracted significant interest as a template material for multiple applications due to its two-dimensional nature and established functionalization chemistries. However, for applications toward stem cell culture and differentiation, GO is often reduced to form reduced graphene oxide, resulting in a loss of oxygen content. Here, we induce a phase transformation in GO and demonstrate its benefits for enhanced stem cell culture and differentiation while conserving the oxygen content. The transformation results in the clustering of oxygen atoms on the GO surface, which greatly improves its ability toward substance adherence and results in enhanced differentiation of human mesenchymal stem cells toward the osteogenic lineage. Moreover, the conjugating ability of modified GO strengthened, which was examined by auxiliary osteogenic growth peptide conjugation. Overall, our work demonstrates GO's potential for stem cell applications while maintaining its oxygen content, which could enable further functionalization and fabrication of novel nano-biointerfaces.

Simultaneous drug delivery and cellular imaging using graphene oxide.

Graphene oxide (GO), a derivative of graphene, and its related nanomaterials have attracted much attention in recent years due to the excellent biocompatibility and large surface area of GO with abundant oxygen functional groups, which further enable it to serve as a nano-bio interface. Herein, we demonstrate the induction of blue fluorescence in GO suspensions via a mild thermal annealing procedure. Additionally, this procedure preserves the oxygen functional groups on the graphene plane which enables the conjugation of cancer drugs without obvious cytotoxicity. Consequently, we demonstrate the capability of GO to simultaneously play the dual-role of a: (i) cellular imaging agent and (ii) drug delivery agent in CT26 cancer cells without the need for additional fluorescent protein labeling. Our method offers a simple, controllable strategy to tune and enhance the fluorescence property of GO, which shows potential for biomedical applications and fundamental studies.