Toward a Microfluidics-Based Home Male Fertility Test

Abstract

Consumers are increasingly interested in knowing more about their own health. One of the most familiar directto-consumer diagnostics tests has been the home pregnancy test. In this issue of Clinical Chemistry, Nosrati et al.(1 ) report their clever and practical approach toward developing a new point-of-care diagnostic test for another reproductive health need-the assessment of male fertility.The authors developed the test using paper, a familiar substrate used in pregnancy tests and the subject of a flurry of recent improvements in microfluidics (2 ). The authors placed at the bottom one laminate layer, and on top, paper layers patterned with wax (3 ). With the paper test they aimed to quantify sperm concentration via a dye that changes color in the presence of an enzyme (diaphorase flavoprotein) that resides within metabolically active human sperm. In one spot on the paper, the sample reacts directly with the dried dye. In a second spot, sperm must swim vertically through a highly viscous buffer and a membrane filter to generate a colorimetric signal. Ten minutes later, a scanner reads the color intensities of the 2 spots, which are used to quantify live and motile sperm concentrations.The paper diagnostic test was assessed on 17 frozen human semen samples obtained from a hospital. Although the performance was promising (for example, it predicted correctly the 1 out of 6 samples having low sperm motility), it is increasingly recognized in the research field of microfluidics that there exists a yawning gap between an academic demonstration and clinical utility. Setting their test apart from many academic demonstrations, these investigators studied the performance of the test over different times of storage and at different humidity levels. Their device, when packaged with desiccant, demonstrated only a small degradation in color change over 16 weeks even in the presence of 22.8 g/m 3 humidity (equivalent to about the maximum humidity at room temperature). For point-of-care use, building a rugged and stable test is critical in translating a promising technology to the clinic.Not all clinical diagnostic tests that can be done in a point-of-care format should be done in a point-of-care format. One driver that justifies a consumer-facing diagnostic test is to provide information that would motivate patients to purchase and use the product. In line with the success of the home pregnancy test, the authors chose an application that would appeal to consumer use. In this case, assessment of male fertility is often initiated by the consumer in cases in which a couple has difficulty conceiving. Moreover, obtaining semen samples would be more comfortably performed at home and in private, which makes this application perfectly suited for home use. Although such considerations may appear more relevant at a later stage of commercialization, understanding them is important at an early research stage to develop a device with proper target specifications (sample type, simplicity of design, resources available) for the intended c...

Home testing for male factor infertility: a review of current options

“…New approaches to home semen testing are attempting to overcome the challenges of current technology and include lensless on-chip microscopy ( 16), paper-based diagnosis (17), digital holography (18), and microfluidic channels (19). Some potential advances could include improved systems that automatically measure multiple parameters and possibly analyze sperm morphology and distinguish normal and abnormal spermatozoa.…”

The emergence of 3D bioprinting in organ-on-chip systems

“…Other systems have been developed to easily observe minute quantities of fluids to better understand and characterize chemical and biological reactions [5]. Microfluidic devices also have translational potential as demonstrated by the development of inexpensive point-of-care diagnostic devices [6] with the ability to identify infectious diseases, such as HIV/AIDS [7] and Lyme disease [8], as well as medical conditions, such as male infertility [9]. These technological advances have influenced the generation of many in vitro biological models through their minimal reagent consumption to achieve scalable results.…”

“Online” and “at-home” versus traditional models of health care: enhancing access or impeding optimal therapeutics?

“…A valid critique of the existing home SA kits includes that they lack adequate quality control, they are vulnerable to false-negative results by the provision of rudimentary quantitative or qualitative results, and they are prone to sample handling errors ( 8 , 9 , 10 ). However, new approaches to home SA testing are overcoming the challenges of current technology by including paper-based diagnosis ( 7 ), smartphone-based computer-assisted SA system ( 11 ), digital holography ( 12 ), and microfluidic channels ( 13 ).…”