Vincent F.S. Tsai

Direct Characterization of Motion-Dependent Parameters of Sperm in a Microfluidic Device: Proof of Principle

BACKGROUND Semen analysis is essential for evaluating male infertility. Besides sperm concentration, other properties, such as motility and morphology, are critical indicators in assessing sperm quality. Nevertheless, rapid and complete assessment of these measures still presents considerable difficulty and involves a range of complex issues. Here we present a microfluidic device capable of quantifying a range of properties of human sperm via the resistive pulse technique (RPT). METHODS An aperture, designed as a long channel, was used to allow the quantification of various properties as sperm swam through. RESULTS The time trace of the voltage drop across the aperture during sperm passage contained a wealth of information: the sperm volume was presented by the amplitude of the induced pulse, the swim velocity was evaluated via the duration, and the beat frequency was calculated from the voltage undulation superposed on the pulse signal. The RPT measurement of swim velocity and beat frequency showed a correlation with the same observation in a microscope (R(2) = 0.94 and 0.70, respectively). CONCLUSIONS The proposed proof of principle enables substantial quantification of the motion-dependent properties of sperm. Because this approach requires only a current/voltage source and data analysis, it is economically advantageous compared with optical methods for characterizing sperm motion. Furthermore, this approach may be used to characterize sperm morphology.

Parasympathetic Influence Plays an Independent and Significant Role in Inducing the Contraction of the Seminal Vesicle of the Rat

OBJECTIVES The role of the parasympathetic pathway in seminal vesicle (SV) contraction has not been well described. The purpose of this study was to study parasympathetic effects, the dominant muscarinic receptors subtype(s), and nitric oxide (NO) effects for SV contraction. METHODS In vivo, SV pressure of mature male Wistar rats were recorded after electric stimulation (ES) of each pelvic nerve (PN; parasympathetic pathway) alone; bilateral PNs simultaneously, the L6 and S1 branches of the left PN; the left PN after ablation of sympathetic influence; the lesser splanchnic nerve (LSN) after ablation of parasympathetic influence; and the LSN after pretreatment of 4 muscarinic receptor antagonists or a NO donor-3-Morpholinosydnonimine (SIN-1). RESULTS ES to the left PN caused frequency-dependent SV contraction, with similar results after ES to the right PN and bilateral PNS. ES to the L6 branch of the left PN caused significantly greater SV response than to the S1 branch. Ablation of sympathetic influence did not affect SV response to parasympathetic stimulation and vice versa. The inhibitory effects of 4-DAMP (M3 antagonist) and atropine (nonselective muscarinic antagonist) on SV response to ES were similar and significantly greater than those of pirenzepine (M1 antagonist) and methoctramine (M2 antagonist). Pretreatment of SIN-1 partially suppressed the SV response of ES to left PN. CONCLUSIONS ES via the parasympathetic pathway independently induces contraction of rat SV; NO partially suppresses the SV pressure response to parasympathetic ES.

The activation of peripheral 5-HT1A receptors can inhibit seminal vesicle contraction: An in vivo animal study

OBJECTIVES To elucidate the differential effects of stimulating various peripheral 5-HT receptor subtypes on the contractile response of seminal vesicles (SVs) induced by electrical stimulation (ES). METHODS Male Wistar rats (aged 12-14 weeks) were prepared as our previously established model, which allows an intraarterial injection of test agents to directly act on SV. Four selective 5-HT agonists-8-OH-DPAT (5-HT1A), 5-nonyloxytryptamine (5-HT1B), BW723C86 (5-HT2B), and MK-212 (5-HT2C)-were injected at various concentrations (from 10(-8) to 10(-4) mmol/kg). After an injection, the SV contractile response was recorded after ES of lesser splanchnic nerve was applied. Relationships between the concentration of an agonist and its effect on SV contraction were plotted and analyzed. RESULTS The peripheral injection of 5-HT1A agonist had a dose-dependent inhibitory effect on SV contraction and could achieve an inhibition of >50%; the IC50 was 3.16x10(-6) mmol/kg. No significant effects were observed with the peripheral injection of 5-HT1B, 5-HT2B, or 5-HT2C agonist. CONCLUSIONS Our in vivo animal study shows that the activation of peripheral 5-HT1A receptors can inhibit ES-induced SV contraction, whereas the activation of peripheral 5-HT1B, 5-HT2B, or 5-HT2C receptors has no significant effect. The results suggest that the peripheral 5-HT pathway is a potential therapeutic target of the treatment for premature ejaculation.

Determination of Human Penile Electrical Resistance and Implication on Safety for Electrosurgery of Penis

INTRODUCTION Electrosurgery has been a surgical application since the late 19th century. Although many urologists take this daily application for granted, the effects of electrical treatment on penile nerves and vessels have not been well documented. AIM To investigate the electrical characteristics of the penis and erectile tissues and to discover the potential hazards of electrosurgery on the penis. METHODS Measurement of the electrical characteristics of three human penises in order to create models to analyze the effect of electricity on penile nerves and vessels. MAIN OUTCOME MEASURES Electrical resistivity of the penile shaft, electrical current density, and electric field strength on penile nerves and vessels, proportion of generated heat on the penis and electrical current density of the electrosurgery return electrode. RESULTS Electrical resistivity (ρ) of the penile shaft is 127.14 Ω · cm at 500 kHz. Electrical current density (J) of the penis shaft is 71.06 mA/cm(2) , nerve (60.23 mA/cm(2) ), vessel (67.93 mA/cm(2) ), and return electrode (2.11 mA/cm(2) ). Electrical field strength (E) of the whole penis shaft is 9.03 volt/cm. The proportion of generated heat on the penis is four times as much as on other body parts of the circuit. CONCLUSIONS Potential and subclinical injury to erectile tissue caused by electrosurgery on the penis cannot be underestimated. The injury mechanism can be attributed to a thermal (electrical current) effect and a nonthermal (mainly electrical field) effect. Ways to avoid the electrosurgical injury are: using less power (W)/electrical field and less time, biopolar electrosurgery confining the injured area, ligation to achieve hemostasis, and new laser technologies.

Temporal Trend of Newly Diagnosed Incidence, Medical Utilization, and Costs for Pediatric Urolithiasis, 1998-2007: A Nationwide Population-based Study in Taiwan

OBJECTIVE To investigate the trends of newly diagnosed incidence, medical utilization, and medical costs for pediatric urolithiasis in Taiwan. MATERIALS AND METHODS The present study uses the National Health Insurance Research Database, which contains the data of all medical benefit claims from the individuals enrolled in the national and single-payer insurance program in Taiwan. The National Health Insurance covered 22,717,053 enrollees, nearly 99% of Taiwans population. Our analysis includes all subjects aged <18 years with a primary diagnosis of urolithiasis. We analyzed the temporal trend for annual newly diagnosed incidence, medical care visits, and medical costs for pediatric urolithiasis from 1998 to 2007. RESULTS A total of 1474 patients aged <18 years with newly diagnosed urolithiasis were identified, including 719 (48.8%) boys and 755 (51.2%) girls. The overall newly diagnosed rate of urolithiasis in pediatric population was 0.038% in 2007. The peak age stratum of urolithiasis occurrence in 2007 was 15-18 years. The trend of annual newly diagnosed incidences for boys, girls, and all children declined from 1998 to 2007. Furthermore, there were declining trends both in medical costs and annual medical care visits during the study period. CONCLUSION This is the first nationwide population-based study to indicate the declining trends in newly diagnosed rate, medical care visits, and medical costs for pediatric urolithiasis. These findings help to quantify and establish the burden of pediatric urolithiasis. These findings help to quantify and establish the burden of medical care for pediatric urolithiasis and to further refine the medical policy.

A low power high CMRR CMOS instrumentation amplifier for Bio-impedance Spectroscopy

In this paper, a high Common-Mode Rejection Ratio (CMRR) and low power CMOS Instrumentation Amplifier (IA) for use in Bio-impedance Spectroscopy (BIS) is presented. It consists of a complementary Differential Voltage - Current Conveyor (DVCC) that provides the common-mode signal rejection and high input impedance, a Folded - Cascode Operational Transconductance Amplifier (FC-OTA) that serves as a gain stage, and a high pass filter built using a PMOS pseudo-resistor. The IA was implemented using TSMC 0.35μm 2P4M Polycide Technology and simulations were carried out using HSPICE. The designed IA features a CMRR of 120.2dB, a differential input impedance of 102.3MΩ, and a common-mode input impedance of 41.3MΩ both at 50kHz, while dissipating an average static power of 290μW.

A wideband current source for System-on-Chip Bio-Impedance Spectroscopy using a CCII drive and Pseudo-Resistor feedback

In this paper, a wideband Current Source (CS) for System on Chip (SoC) Bio-Impedance Spectroscopy (BIS) application is presented. The circuit consists of a load-in loop inverting amplifier current source back-end with a PMOS Pseudo-Resistor (PR) feedback, and a Norton current source front-end drive in the form of a Second Generation Current Conveyor (CCII). The load-in-loop structure allows a differential interface to the Sample Under Study (SUT) permitting the four-point probe interface. The use of a PR array results in the creation of a high impedance feedback while consuming small chip area. The CCII drive increases the output impedance of the CS towards the MHz range. Comparison of 6 load-in-loop CS (LL-CS) structures confirm the performance of our design in terms of output impedance, and excitation current precision over a wide frequency range covering the beta-dispersion range of BIS (~10MHz). The LL-CS structures are realized using TSMC 0.35um CMOS 2P4M Mixed Mode Technology.

The Biochemical and Pathological Correlates of Successful Semen Cryopreservation From Patients With Testicular Cancer: A Single Tertiary Center Experience

OBJECTIVE To determine the predictors for success with regard to semen cryopreservation and good semen quality of patients with testicular cancer. MATERIALS AND METHODS A total of 50 men (aged 16-36 years) with testicular cancer, referred for semen cryopreservation prior to gonadotoxic treatment, were included. Age, alpha fetal protein (α-FP), beta human chorionic gonadotropin, lactate dehydrogenase, clinical staging, tumor volume, and pathological reports were evaluated as correlates of successful semen cryopreservation and good semen quality. RESULTS The overall success rate was 52%. α-FP (4113.1 ng/mL vs 81.2 ng/mL) and tumor volume (77.7 mL vs 25.5 mL) were significantly higher in the failure group as compared to the success group. The seminoma to nonseminomatous germ cell tumor ratio was lower in the failure group as compared to the success group (9/17 vs 3/21). There was nearly a significant difference (P = .066). The optimal cutoff value for α-FP > 1000 ng/mL showed the highest Youden index (0.689) and resulted in a sensitivity of 0.625 and specificity of 1.0 for predicting poor outcome. In terms of multivariate analysis, the α-FP (P = .013), tumor volume (P = .047), and α-FP > 1000 ng/mL (P  =  .010) were significantly associated with poor semen quality and failure to preserve semen. Sperm quality was found to be higher in the seminoma versus the nonseminomatous germ cell tumor patients in: sperm concentration (21.5 million/mL vs 11.8 million/mL, P  <  .027). Furthermore, tumor volume is correlated to α-FP (P  =  .018) and is weakly correlated to lactate dehydrogenase (P = .067) CONCLUSION: Elevated α-FP and tumor volume are independently poor factors for semen quality and semen cryopreservation. In clinical use, α-FP is a noninvasive tool to predict the success of semen cryopreservation and patients with α-FP > 1000 ng/mL should be informed of the higher risk of poor semen quality and semen cryopreservation concerns.

Design of a multi-frequency bio-impedance spectroscopy system analog front-end and digital back-end with on-chip implementation

In this paper, the design of a Bio-Impedance Spectroscopy system is presented. The system consists of a Direct Digital Synthesis Sine-Wave Generator (DDS-SWG), an Analog Front-End (AFE), an Analog-Digital Converter (ADC), and a Digital Back-End implemented using a Field Programmable Gate Array (FPGA). The FPGA also drives the ADC, the DDS-SWG, and the LCD. The AFE consists of a high output impedance Load-In-Loop Current Source (LL-CS) and a set of High Common-Mode Rejection Ratio (CMRR) Instrumentation Amplifiers (IA). It uses a simple and straightforward impedance extraction algorithm using just division and constant multiplication. The CMOS implementation of the AFE using the TSMC 0.35um 2P4M is also presented. The system forms part of a platform that aims to predict a urolithiasis (urinary stone) event.

Design of a multi-sensor readout chip for amperometric, potentiometric, impedometric, and colorimetric bio-sensor applications

Point-of-Care Testing (POCT) devices are being deployed to provide personalized healthcare monitoring or for remote monitoring whenever there is no accessible medical facility. In line with POCT, Lab-on-a Paper or Lab-on-a-Chip devices are taking flight. These include the hybrid of the sensor and readout circuit fabricated into a chip. To date, there is no single chip solution that harmonizes the four electrochemical sensing modalities which is the contribution of this work. The design of a multi-sensor readout chip is presented; this is composed of amperometric, potentiometric, impedometric, and colorimetric readout circuits implemented on TSMC 0.18 µm 1P6M technology. The chip can be used to implement a POCT to assist a patient in assessing the condition of his urinary system through urine quality indicators such as: pH value and ionic concentration of calcium (Ca2+) via potentiometric sensing; uric acid, citric acid, and calcium oxalate concentrations via amperometric sensing; osmolality or total dissolved salts through impedometric sensing; and urine turbidity, color and crystallization through its optical properties. The readout circuit designs for diversified sensing mechanisms were developed and investigated in this paper. In addition, a power savings of ∼60dB can be achieved when all the circuits of the proposed chip are disabled. The sub-circuit enable was implemented using PMOS pass transistors. Non-simultaneous sub-circuit enable both reduces the power budget and prevents the inter-sensor interference or cross-talk.