Infectious diseases are a major global health issue. Diagnosis is a critical first step in effectively managing their spread. Paper-based microfluidic diagnostics first emerged in 2007 as a low-cost alternative to conventional laboratory testing, with the goal of improving accessibility to medical diagnostics in developing countries. In this review, we examine the advances in paper-based microfluidic diagnostics for medical diagnosis in the context of global health from 2007 to 2016. The theory of fluid transport in paper is first presented. The next section examines the strategies that have been employed to control fluid and analyte transport in paper-based assays. Tasks such as mixing, timing, and sequential fluid delivery have been achieved in paper and have enabled analytical capabilities comparable to those of conventional laboratory methods. The following section examines paper-based sample processing and analysis. The most impactful advancement here has been the translation of nucleic acid analysis...

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Turning the Page: Advancing Paper-Based Microfluidics for Broad Diagnostic Application.

Dewhurst's textbook of obstetrics and gynaecology

Infertility is a growing global health issue with far-reaching socioeconomic implications. A downward trend in male fertility highlights the acute need for affordable and accessible diagnosis and treatment. Assisted reproductive technologies are effective in treating male infertility, but their success rate has plateaued at ∼33% per cycle. Many emerging opportunities exist for microfluidics - a mature technology in other biomedical areas - in male infertility diagnosis and treatment, and promising microfluidic approaches are under investigation for addressing male infertility. Microfluidic approaches can improve our fundamental understanding of sperm motion, and developments in microfluidic devices that use microfabrication and sperm behaviour can aid semen analysis and sperm selection. Many burgeoning possibilities exist for engineers, biologists, and clinicians to improve current practices for infertility diagnosis and treatment. The most promising avenues have the potential to improve medical practice, moving innovations from research laboratories to clinics and patients in the near future.

Microfluidics for sperm analysis and selection

The diagnosis of infectious diseases is entering a new and interesting phase. Technologies based on paper microfluidics, coupled to developments in isothermal amplification of Nucleic Acids (NAs) raise opportunities for bringing the methods of molecular biology in the field, in a low setting environment. A lot of work has been performed in the domain over the last few years and the landscape of contributions is rich and diverse. Most often, the level of sample preparation differs, along with the sample nature, the amplification and detection methods, and the design of the device, among other features. In this review, we attempt to offer a structured description of the state of the art. The domain is not mature and there exist bottlenecks that hamper the realization of Nucleic Acid Amplification Tests (NAATs) complying with the constraints of the field in low and middle income countries. In this domain however, the pace of progress is impressively fast. This review is written for a broad Lab on a Chip audience.

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Paper microfluidics for nucleic acid amplification testing (NAAT) of infectious diseases

The fields of assisted reproductive technology (ART) and in vitro fertilization (IVF) have progressed rapidly, yet still need further improvements. Microfluidic technology can incorporate various ART procedures such as embryo/gamete (sperm/oocyte) analysis, sorting, manipulation, culture, and monitoring. The introduction of paper‐based and droplet‐based microfluidics further improves the commercialization potential of this technology. The progress in 3D printing technology allows for the integration of microfluidics with tissue engineering that may revolutionize current practices in biology and medicine. This review categorizes ART methods according to continuous‐flow microfluidics, paper‐based microfluidics, droplet‐based microfluidics, and organ‐on‐a‐chip. The advances are summarized and potential opportunities in infertility diagnosis, sperm selection, sperm guidance, oocyte selection, insemination, embryo culture, embryo monitoring, and cryopreservation are identified. While some advances of continuous‐flow microfluidics for ART have already been reviewed, other microfluidic techniques are still in their early stages. It is envisioned that advances in droplet‐based microfluidics, especially digital microfluidics, will allow for more progress in human IVF, particularly single embryo transfer. Droplet‐based microfluidics may also lead to fully integrated and high‐throughput platforms for animal IVF. Recent advances in organ‐on‐a‐chip including ovary/uterus/oviduct‐on‐chip platforms hold promise for the integration of the whole human reproductive system‐on‐a‐chip for clinical applications.

Advances in Microfluidics-Based Assisted Reproductive Technology: From Sperm Sorter to Reproductive System-on-a-Chip

Male infertility, which amounts to half of all infertility cases, is a serious problem worldwide. The percentage of fertility-related patients in sub-Saharan African countries is higher than that for the developed countries. In low-resource countries, examination of sperm characteristics for male infertility cannot be undertaken because of poor clinical access. To evaluate male fertility in assisted reproductive medicine laboratories, the numbers of motile human sperm, the degree of sperm motility, and sperm morphology have been commonly analyzed using a microscope. It is challenging to monitor the health status of human sperm in resource-limited or remote settings for two primary reasons: (1) high capital cost (equipment for currently accepted procedural standard), and (2) complexity of the currently accepted procedural standard used to simultaneously measure human sperm concentration and motility by skillful embryologists. Determining the health status of human sperm in order to evaluate fertilization capacity using various types of low-cost, easy-to-use, and rapid devices (or systems) is a longstanding but interesting biotechnologically relevant issue in various scientific communities such as male reproduction. Furthering such efforts will inherently influence birth rate in both developed and developing nations. We have demonstrated an inexpensive but robust and easy-to-handle device for monitoring the health status of human sperm made by patterning a piece of paper and measuring the activity of a specific enzyme—a simple and elegant solution. After applying semen to the hydrophilic center circle of our patterned paper, a thiazine assay can be used to suggest sperm concentration in semen, and a tetrazolium-based colorimetric assay (MTT assay) data can be used to help estimate the percentage of motile human sperm (sperm motility) in semen based on the character that motile human sperm moved in and on the paper. Using this paper-based device, we can evaluate fertility levels without consulting doctors and use our assay to compare results with World Health Organization (WHO) reference values for sperm concentration (>2×107) and motility (>50 %). The duration and cost of one entire test are 30 min and 0.1 USD, respectively. We believe that this paper-based assay system would be useful for fertility checks based on WHO references, without need of a microscope, at home. Using this assay method, males in developed or developing countries who are reluctant or unable to consult assisted reproductive technologies clinics can self-analyze their sperm characteristics. We further note that our approach adheres to WHO regulations, especially in regard to in vitro diagnostic device performance with an associated diagnostic algorithm to enhance diagnostic accuracy (compared with just one diagnostic output), and we wish to emphasize that our research could significantly advance a broad range of diagnostic developments including paper-based diagnostic devices, in vitro diagnostic devices, and diagnosis of other diseases in various divisions of translational medicine. These results, we believe, will be of interest to a wide scientific audience working in materials science (biomaterials), chemistry (analytical and clinical), lab-on-a-chip technologies (the development of diagnostic tools), reproductive medicine, bioengineering, and translational medicine.

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Paper-based diagnostic devices for evaluating the quality of human sperm

http://www.thelancet.com/article/S2589750021002788/pdf

Wenqian Li

Papers

Paper-based diagnostic devices for evaluating the quality of human sperm

Deep learning-enabled pelvic ultrasound images for accurate diagnosis of ovarian cancer in China: a retrospective, multicentre, diagnostic study.