An Ultrasonically Actuated Silicon-Microprobe-Based Testicular Tubule Assay

Microdissection testicular sperm extraction (TESE) is an invasive surgical procedure in which sparsely located healthy larger diameter tubules carrying viable spermatazoa are identified by visual examination of the seminiferous tubules of the infertile testis under a microscope, and biopsies of regions of interest are performed. In this paper, we report on microfabricated silicon microprobes integrated with an ultrasonic horn actuator and strain gauges for microdissection probe-TESE (MP-TESE) surgery. The microprobes, with axial-force-sensitive polysilicon strain gauges, have high force sensitivity (-0.4 V/N). The probes were used to detect the boundaries between seminiferous tubules, thus enabling identification of individual tubule diameters. Insertion experiments were performed on rat testis tissue, and by monitoring the tubule puncture in the recorded force, we were able to estimate the average diameter ~ 41.2 plusmn 1.6 mum of the sperm-carrying tubules in samples. We have also demonstrated the ability to sense the existence of larger tubules embedded in a mess of thinner tubules, using an analytically calculated expression for the distribution of sizes measured by the microprobe. This information is important in MP-TESE to distinguish tubules with and without fertile sperm, potentially eliminating the large incision currently required for optical spermatazoa localization.

[1]  E. Steinberger,et al.  Quantitative analysis of the seminiferous epithelium in human testicular biopsies, and the relation of spermatogenesis to sperm density. , 1978, Fertility and sterility.

[2]  S. Silber,et al.  Quantitative analysis of testicle biopsy: determination of partial obstruction and prediction of sperm count after surgery for obstruction. , 1981, Fertility and sterility.

[3]  Allison M. Okamura,et al.  Force modeling for needle insertion into soft tissue , 2004, IEEE Transactions on Biomedical Engineering.

[4]  Xi Chen,et al.  Ultrasonically Actuated Silicon Microprobes for Cardiac Signal Recording , 2006, IEEE Transactions on Biomedical Engineering.

[5]  Sung June Kim,et al.  A micromachined silicon depth probe for multichannel neural recording , 2000, IEEE Transactions on Biomedical Engineering.

[6]  P. Devroey,et al.  Sertoli cell only revisited. , 1995, Human reproduction.

[7]  James M. Bower,et al.  Plasma-etched neural probes , 1996 .

[8]  K. Wise,et al.  A high-yield IC-compatible multichannel recording array , 1985, IEEE Transactions on Electron Devices.

[9]  G. Lindop,et al.  An assessment of the distortion of arteries due to sectioning in endomyocardial biopsios , 1997, The Journal of pathology.

[10]  E. Obermeier,et al.  Characteristics of polysilicon layers and their application in sensors , 1986 .

[11]  F. Piefke Chord length distribution of the ellipse , 1979 .

[12]  A. Lal,et al.  Micromachined Ultrasonic Ophthalmic Microsurgical Tool with Integrated Pressure Sensor , 2001 .

[13]  Z. Nagy,et al.  The use of epididymal and testicular spermatozoa for intracytoplasmic sperm injection: the genetic implications for male infertility. , 1995, Human reproduction.

[14]  K. Wise,et al.  An implantable multielectrode array with on-chip signal processing , 1986 .

[15]  P. Schlegel Testicular sperm extraction: microdissection improves sperm yield with minimal tissue excision. , 1999, Human reproduction.

[16]  I. Craft,et al.  Testicular needle aspiration as an alternative to biopsy for the assessment of spermatogenesis. , 1997, Human reproduction.

[17]  Z. Nagy,et al.  High fertilization and pregnancy rate after intracytoplasmic sperm injection with spermatozoa obtained from testicle biopsy. , 1995, Human reproduction.

[18]  S. Friedler,et al.  Testicular sperm retrieval by percutaneous fine needle sperm aspiration compared with testicular sperm extraction by open biopsy in men with non-obstructive azoospermia. , 1997, Human reproduction.

[19]  Amit Lal,et al.  A multifunctional silicon-based microscale surgical system , 2001 .

[20]  Arianna Menciassi,et al.  Force feedback-based microinstrument for measuring tissue properties and pulse in microsurgery , 2001, Proceedings 2001 ICRA. IEEE International Conference on Robotics and Automation (Cat. No.01CH37164).

[21]  Wamadeva Balachandran,et al.  Silicon-based microelectrodes for neurophysiology fabricated using a gold metallization/nitride passivation system , 1996 .

[22]  N. Zaninovic,et al.  Testicular sperm extraction with intracytoplasmic sperm injection for nonobstructive azoospermia. , 1997, Urology.

[23]  Z. Nagy,et al.  Normal pregnancies resulting from testicular sperm extraction and intracytoplasmic sperm injection for azoospermia due to maturation arrest. , 1996, Fertility and sterility.

[24]  Z. Nagy,et al.  Distribution of spermatogenesis in the testicles of azoospermic men: the presence or absence of spermatids in the testes of men with germinal failure. , 1997, Human reproduction.

[25]  Septimiu E. Salcudean,et al.  Needle insertion modelling and simulation , 2002, Proceedings 2002 IEEE International Conference on Robotics and Automation (Cat. No.02CH37292).

[26]  A. Christensen,et al.  Morphometric studies on rat seminiferous tubules. , 1982, The American journal of anatomy.

[27]  Z. Nagy,et al.  Fertilization and early embryology: Ongoing pregnancies and birth after intracytoplasmic sperm injection with frozen—thawed epididymal spermatozoa , 1995 .

[28]  S. Silber Microsurgical TESE and the distribution of spermatogenesis in non-obstructive azoospermia. , 2000, Human reproduction.