Point‐of‐care semen analysis of patients with infertility via smartphone and colorimetric paper‐based diagnostic device

Abstract

Male infertility affects millions of males worldwide and is rising in prevalence due to social and environmental conditions. However, men often feel too embarrassed to receive a semen analysis in the hospital due to social stigmas. To overcome this problem, we developed a 3‐(4,5‐Dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2H‐tetrazolium bromide test strip to distinguish semen samples with low total motile sperm concentration from those with normal motile sperm concentration. This is a point‐of‐care colorimetric semen analytical method with a one‐step, inexpensive, equipment‐free evaluation process, and adequate accuracy validated in a 42‐sample clinical trial. In this study, results were evaluated visually and with a smartphone application. Using visual observation methods, the area under the curve (AUC) was 0.71 (95% of confidence interval = 0.55–0.86; p = 0.021), sensitivity was 41%, specificity was 95%, positive predictive value was 90%, negative predictive value (NPV) was 59.4%, and accuracy was 67%. Using a smartphone recording and analytical system, AUC was 0.766 (95% of confidence interval = 0.612–0.92; p = 0.003), sensitivity was 96%, specificity was 65%, PPV was 75%, NPV was 92.9%, and accuracy was 80.9%. This work demonstrated a screening tool that could elevate semen analysis to the level of routine healthcare and provide for private, in‐home self‐assessment.

Detection of Microorganisms in Body Fluids via MTT-PMS Assay

“…We previously successfully integrated the MTT assay into a low-cost, laboratory-free, easy-to-use, paper-based device to evaluate porcine sperm motility. The MTT assay was embedded on a designed paper-based device, and the colorimetric results could be evaluated via a smartphone application [ 60 , 61 , 62 , 63 ]. The integration of this technique into a paper-based device that can be analyzed with a smartphone makes it highly portable and accessible for use in local clinics and communities.…”

Recent Microfluidic Innovations for Sperm Sorting

“…Several paper-based microfluidic devices for sperm analysis are reported in the literature; however, they are not intended to be used for sperm sorting. For example, a couple of MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)-based colorimetric paper assays using smartphone imaging were developed to assess total motile sperm concentration at home [94][95][96]. Moreover, Nosrati and colleagues developed a novel paper-based sperm chromatin integrity analysis, which measured DNA fragmentation and packaging [97].…”

Small-volume detection: platform developments for clinically-relevant applications

“…Furthermore, a biochemical-based POC semen analytical device that combined a microfluidic paper plate with a colorimetric reaction has been developed: Matsuura developed paper-based assays for sperm counting and sperm motility assessment [ 118 , 119 ]. Tsao developed a paper-based MTT assay to differentiate normal and low total motile sperm concentration for semen screening by self-assessment [ 120 ]. Using a different approach than traditional image-based analytical techniques, these biochemical-based POC diagnostic devices all loaded the reaction reagent onto the paper platform first and then directly inserted the test strips into the semen sample, which largely reduced the duration and cost (0.1 USD per test) for semen analysis (Fig.…”

“…b The colorimetric results of the strip, which can be interpreted by visual observation or by smartphone-based recording and analytical system. MTT 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2 H -tetrazolium bromide [ 120 ] …”