This article reviews state-of-the-art microfluidic biosensors of nucleic acids and proteins for pointof-care (POC) diagnostics. Microfluidics is capable of analyzing small sample volumes (10 -9 -10 -18 l) and minimizing costly reagent consumption as well as automating sample preparation and reducing processing time. The merger of microfluidics and advanced biosensor technologies offers new promises for POC diagnostics, including high-throughput analysis, portability and disposability. However, this merger also imposes technological challenges on biosensors, such as high sensitivity and selectivity requirements with sample volumes orders of magnitude smaller than those of conventional practices, false response errors due to non-specific adsorption, and integrability with other necessary modules. There have been many prior review articles on microfluidic-based biosensors, and this review focuses on the recent progress in last 5 years. Herein, we review general technologies of DNA and protein biosensors. Then, recent advances on the coupling of the biosensors to microfluidics are highlighted. Finally, we discuss the key challenges and potential solutions for transforming microfluidic biosensors into POC diagnostic applications.

INTRODUCTION AND OBJECTIVES: Epidemiological studies of hypogonadism have unequivocally shown that the majority of men with clinically low testosterone levels have secondary hypogonadism. This disorder is primarily associated with being overweight (BMI > 25) or obese (BMI > 30) and is neither idiopathic nor due to normal aging. The secondary hypogonadal male has functional but under stimulated testes. These men are typically fertile but exhibit low total testosterone that results from sub-optimal stimulation of the Leydig cells due to suppressed LH secretions by the pituitary. The reduced LH release in turn is due to negative feedback of estrogen on the hypothalamus-pituitary axis.METHODS: Two double-blind, double-dummy, placebocontrolled, 16 week studies in 256 men. Men less than 60 years of age, with BMI > 25 were enrolled if they exhibited sperm counts in the normal range at baseline (> 15 million/mL) and morning testosterone of < 300 ng/dL) RESULTS: EndroxalÔ was found to restore T levels in the majority of secondary hypogonadal men ( Table 1). The magnitude of the effect was much greater and more consistent than with Androgel. In contrast to the characteristic and well-documented suppression of spermatogenesis with Androgel, EndroxalÔ exhibited no negative effect on spermatogenesis compared to placebo.CONCLUSIONS: EndroxalÔ is a high affinity estrogen antagonist (IC50:16nM) with substantially higher antagonist activity than its isomer zuclomiphene (IC50:610nM). The zu isomer, comprising up to 40% of commercial clomiphene, is poorly metabolized and accumulates (10 fold greater than enclomiphene). These pharmacological and pharmacokinetic differences between the two isomers could lead to and improved therapeutic window for EndroxalÔ over clomiphene.Overall, the data show that T restoration with EndroxalÔ could provide an advantageous clinical profile over gel-induced T replacement.