Male infertility and microchips.

Silicon, glass, and polymer microchip devices (lab-ona-chip) have found a diverse range of analytical and preparative applications (1 ). Prominent applications include protein and nucleic acid electrophoresis (2 ), PCR (3, 4 ), and cellular analysis (5 ). Microchip devices have also demonstrated promise in semen analysis as part of the evaluation of male infertility. The key parameters of semen analysis are semen volume, sperm concentration, sperm motility, and sperm morphology (6 ). These parameters are usually examined in modern clinical laboratories with a microscope coupled to an image-analysis system (computer-assisted sperm analysis); however, there have been various attempts to automate and/or miniaturize the examination of sperm in the context of microfluidic chips. The most basic fluidic devices have lanes in which the sperm can be observed and compared with respect to their ability to swim. These lanes are in essence fabricated microchannel racetracks (7, 8 ). More-complex devices not only add architectural complexity to the racetracks but also add electrical components that facilitate sperm counting and motility measurements (e.g., the “fertility chip”) (9 ). In this issue of Clinical Chemistry, Yu-An Chen and colleagues (10 ) describe their demonstration of a novel microfluidic device that has the potential to measure many of the key parameters in semen analysis. Building on a previous sperm microchip design (11 ), the authors have created their current device, a glass– polydimethylsiloxane microfabricated chip; the key component is a straight channel (46 m long, 7 m wide, and 11 m deep) connected to 3 reservoirs. Two of the reservoirs contain electrodes. As the sperm travel through the device, their movement through the channel changes the measured voltage according to various properties intrinsic to the sperm. A key advancement of the device is the use of a resistive-pulse technique to determine the tail beat frequency and the morphology of the sperm head. The tail beat frequency was measured by monitoring changes in the electrical pulse that correspond to sperm head movement as the sperm traverses the channel. The authors did not examine sperm morphology (e.g., normal head, double-headed, misshapen head) directly in the study, but they demonstrated that variously shaped particles representative of sperm heads change the electrical potential, depending on their shape. The closer to a true spherical shape that the particles became, the larger the drop in the electrical potential. The theory for this relationship is that the more spherical particles are more resistant to current flow. Indeed, the ability to use impedance to measure sperm shape is analogous to early work in using a Coulter counter to determine red blood cell morphology (12 ). With the added functionality of tail beat frequency and head morphology, the authors of the present study have now demonstrated the ability to combine the key parameters of semen analysis on a microfluidic chip that requires only electrical measurements. The use of the Coulter principle to evaluate sperm is not new (13, 14 ), but the researchers in this study have demonstrated that a single microchip device based on the Coulter principle can perform the key elements of sperm evaluation. Furthermore, their miniaturized system does not require optical and/or visual measurements. The resulting device provides a potential step in the continued evolution away from optical/ visual devices for semen testing. Many studies, such as that provided by Chen and colleagues (10 ), illustrate compelling advantages of microchip-based analyses; however, the next step in commercializing these prototype devices has been exceedingly slow. One of the many hurdles to the commercialization of microchip devices for sperm analysis, and perhaps all lab-on-a-chip technologies, is the lack of a commonly available interface for these chips. In essence, the innovative technology for these miniaturized devices lies in the chip, but the interface during the prototype phase of development is a combination of rudimentary laboratory equipment (e.g., syringe injector, power source, voltmeter). Thus, the cost of commercial development includes not only the key microchip technology but also the enabling ancillary equipment. One step toward facilitating commercialization is for the microfluidics field to migrate to commonly available platforms, thus increasing compatibility with existing off-the-shelf instruments (so-called 1 Department of Pathology, University of Texas Southwestern Medical Center and Children’s Medical Center, Dallas, TX; 2 Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, PA. * Address correspondence to this author at: Department of Pathology, University of Texas Southwestern Medical Center and Children’s Medical Center, 1935 Medical District Dr., Dallas, TX 75235. Fax 214-456-4713; e-mail [email protected]. Received December 19, 2012; accepted December 21, 2012. Previously published online at DOI: 10.1373/clinchem.2012.200394 Clinical Chemistry 59:3 457–458 (2013) Editorials