Deep Learning-Enabled Technologies for Bioimage Analysis.

Deep learning (DL) is a subfield of machine learning (ML), which has recently demonstrated its potency to significantly improve the quantification and classification workflows in biomedical and clinical applications. Among the end applications profoundly benefitting from DL, cellular morphology quantification is one of the pioneers. Here, we first briefly explain fundamental concepts in DL and then we review some of the emerging DL-enabled applications in cell morphology quantification in the fields of embryology, point-of-care ovulation testing, as a predictive tool for fetal heart pregnancy, cancer diagnostics via classification of cancer histology images, autosomal polycystic kidney disease, and chronic kidney diseases.

Increasing the packing density of assays in paper-based microfluidic devices.

Paper-based devices have a wide range of applications in point-of-care diagnostics, environmental analysis, and food monitoring. Paper-based devices can be deployed to resource-limited countries and remote settings in developed countries. Paper-based point-of-care devices can provide access to diagnostic assays without significant user training to perform the tests accurately and timely. The market penetration of paper-based assays requires decreased device fabrication costs, including larger packing density of assays (i.e., closely packed features) and minimization of assay reagents. In this review, we discuss fabrication methods that allow for increasing packing density and generating closely packed features in paper-based devices. To ensure that the paper-based device is low-cost, advanced fabrication methods have been developed for the mass production of closely packed assays. These emerging methods will enable minimizing the volume of required samples (e.g., liquid biopsies) and reagents in paper-based microfluidic devices.

Plant-Based Scaffolds in Tissue Engineering.

A wide range of platforms has been developed for 3D culture of cells in vitro to aggregate and align cells to resemble in vivo conditions in order to enhance communication between cells and promote differentiation. The cellulose skeleton of plant tissue can serve as an attainable scaffold for mammalian cells after decellularization, which is advantageous when compared to synthetic polymers or animal-derived scaffolds. Adjustable variables to modify the physical and biochemical properties of the resulting scaffolds include the protocol for the sodium dodecyl sulfate (SDS)-based decellularization procedure, surface coatings for cell attachment, plant type for decellularization, differentiation media, and integrity and shape of the substrate. These tunable cellulose platforms can host a wide range of mammalian cell types from muscle to bone cells, as well as malignancies. Here, fundamentals and applications of decellularized plant-based scaffolds are discussed. These biocompatible, naturally perfused, tunable, and easily prepared decellularized scaffolds may allow eco-friendly manufacturing frameworks for application in tissue engineering and organs-on-a-chip.

Pentapeptide IKVAV-engineered hydrogels for neural stem cell attachment.

Spinal cord injury remains irreversible with current treatment paradigms, due to the inability to rebuild the regenerative environment for neurons after injury. Neural tissue engineering that encapsulates the neural stem/progenitor cells within an artificial scaffold provides a possibility to regenerate neurons for spinal cord injury repair. The attachment and survival of these neural cells usually require similar microenvironments to the extracellular matrix for support. Here, a three-dimensional pentapeptide IKVAV-functionalized poly(lactide ethylene oxide fumarate) (PLEOF) hydrogel is developed. In vitro tests demonstrate that the IKVAV-PLEOF hydrogels are biodegradable and hemo-biocompatible. This IKVAV-PLEOF hydrogel is shown to support neural stem cell attachment, growth, proliferation, and differentiation. Additionally, the neural stem cells could be readily formed as spheroids that subsequently encapsulated, attached, and proliferated within the three-dimensional hydrogel constructs. Additionally, an in vivo test confirms the biodegradability and biocompatibility of the IKVAV-PLEOF hydrogels revealing that the hydrogels biodegrade, new blood vessels form, and few inflammatory responses are observed after 4-week implantation. The neural stem cell spheroid-laden hydrogels may have further implications in spinal cord injury regenerative and brain repair in neural tissue engineering.

Machine learning-enabled multiplexed microfluidic sensors.

High-throughput, cost-effective, and portable devices can enhance the performance of point-of-care tests. Such devices are able to acquire images from samples at a high rate in combination with microfluidic chips in point-of-care applications. However, interpreting and analyzing the large amount of acquired data is not only a labor-intensive and time-consuming process, but also prone to the bias of the user and low accuracy. Integrating machine learning (ML) with the image acquisition capability of smartphones as well as increasing computing power could address the need for high-throughput, accurate, and automatized detection, data processing, and quantification of results. Here, ML-supported diagnostic technologies are presented. These technologies include quantification of colorimetric tests, classification of biological samples (cells and sperms), soft sensors, assay type detection, and recognition of the fluid properties. Challenges regarding the implementation of ML methods, including the required number of data points, image acquisition prerequisites, and execution of data-limited experiments are also discussed.

Healthcare Applications of pH-Sensitive Hydrogel-Based Devices: A Review.

pH-sensitive hydrogels have been developed greatly over the past few years. This has been possible due to the synthesis of new hydrogel systems with increased sensitivity - a sensitivity of up to 10-5 pH units has already been established. Recently, pH-sensitive hydrogels have shown to be very useful in biomedical applications, such as targeted cancer treatment and treatment of skin lesions. Prolonged drug release has been made available through the use of such hydrogels. The synthesis of pH-sensitive hydrogels is also quick and cost-effective. This review presents a background on the properties of pH-sensitive hydrogels and discusses some of the hydrogels with different sensitivity ranges and their possible applications. A range of synthesis processes have also been briefly introduced along with the fabrication of different structures such as microcantilevers and contact lenses.

The regulation of mobile medical applications.

The rapidly expanding number of mobile medical applications have the potential to transform the patient-healthcare provider relationship by improving the turnaround time and reducing costs. In September 2013, the U.S. Food and Drug Administration (FDA) issued guidance to regulate these applications and protect consumers by minimising the risks associated with their unintended use. This guidance distinguishes between the subset of mobile medical apps which may be subject to regulation and those that are not. The marketing claims of the application determine the intent. Areas of concern include compliance with regular updates of the operating systems and of the mobile medical apps themselves. In this article, we explain the essence of this FDA guidance by providing examples and evaluating the impact on academia, industry and other key stakeholders, such as patients and clinicians. Our assessment indicates that awareness and incorporation of the guidelines into product development can hasten the commercialisation and market entry process. Furthermore, potential obstacles have been discussed and directions for future development suggested.

Paper-based microfluidic point-of-care diagnostic devices.

Dipstick and lateral-flow formats have dominated rapid diagnostics over the last three decades. These formats gained popularity in the consumer markets due to their compactness, portability and facile interpretation without external instrumentation. However, lack of quantitation in measurements has challenged the demand of existing assay formats in consumer markets. Recently, paper-based microfluidics has emerged as a multiplexable point-of-care platform which might transcend the capabilities of existing assays in resource-limited settings. However, paper-based microfluidics can enable fluid handling and quantitative analysis for potential applications in healthcare, veterinary medicine, environmental monitoring and food safety. Currently, in its early development stages, paper-based microfluidics is considered a low-cost, lightweight, and disposable technology. The aim of this review is to discuss: (1) fabrication of paper-based microfluidic devices, (2) functionalisation of microfluidic components to increase the capabilities and the performance, (3) introduction of existing detection techniques to the paper platform and (4) exploration of extracting quantitative readouts via handheld devices and camera phones. Additionally, this review includes challenges to scaling up, commercialisation and regulatory issues. The factors which limit paper-based microfluidic devices to become real world products and future directions are also identified.

Iridescence in Meat Caused by Surface Gratings.

The photonic structure of cut muscle tissues reveals that the well-ordered gratings diffract light, producing iridescent colours. Cut fibrils protruding from the muscle surface create a two-dimensional periodic array, which diffract light at specific wavelengths upon illumination. However, this photonic effect misleads consumers in a negative way to relate the optical phenomenon with the quality of the product. Here we discuss the fundamentals of this optical phenomenon and demonstrate a methodology for quantitatively measuring iridescence caused by diffraction gratings of muscle tissue surface of pork (Sus scrofa domesticus) using reflection spectrophotometry. Iridescence was discussed theoretically as a light phenomenon and spectral measurements were taken from the gratings and monitored in real time during controlled drying. The findings show that the intensity of diffraction diminishes as the surface grating was dried with an air flow at 50 °C for 2 min while the diffracted light wavelength was at 585 ± 9 nm. Our findings indicate that the diffraction may be caused by a blazed surface grating. The implications of the study include providing guidelines to minimise the iridescence by altering the surface microstructure, and in consequence, removing the optical effect.