Dual-side and three-dimensional microelectrode arrays fabricated from ultra-thin silicon substrates

A method for fabricating planar implantable microelectrode arrays was demonstrated using a process that relied on ultra-thin silicon substrates, which ranged in thickness from 25 to 50 µm. The challenge of handling these fragile materials was met via a temporary substrate support mechanism. In order to compensate for putative electrical shielding of extracellular neuronal fields, separately addressable electrode arrays were defined on each side of the silicon device. Deep reactive ion etching was employed to create sharp implantable shafts with lengths of up to 5 mm. The devices were flip-chip bonded onto printed circuit boards (PCBs) by means of an anisotropic conductive adhesive film. This scalable assembly technique enabled three-dimensional (3D) integration through formation of stacks of multiple silicon and PCB layers. Simulations and measurements of microelectrode noise appear to suggest that low impedance surfaces, which could be formed by electrodeposition of gold or other materials, are required to ensure an optimal signal-to-noise ratio as well a low level of interchannel crosstalk

Wake redirection: Comparison of analytical, numerical and experimental models

This paper focuses on wake redirection techniques for wind farm control. Two control strategies are investigated: yaw misalignment and cyclic pitch control. First, analytical formulas are derived for both techniques, with the goal of providing a simple physical interpretation of the behavior of the two methods. Next, more realistic results are obtained by numerical simulations performed with CFD and by experiments conducted with scaled wind turbine models operating in a boundary layer wind tunnel. Comparing the analytical, numerical and experimental models allows for a cross-validation of the results and a better understanding of the two wake redirection techniques. Results indicate that yaw misalignment is more effective than cyclic pitch control in displacing the wake laterally, although the latter may have positive effects on wake recovery

Wiring Nanoscale Biosensors with Piezoelectric Nanomechanical Resonators

Nanoscale integrated circuits and sensors will require methods for unobtrusive interconnection with the macroscopic world to fully realize their potential. We report on a nanoelectromechanical system that may present a solution to the wiring problem by enabling information from multisite sensors to be multiplexed onto a single output line. The basis for this method is a mechanical Fourier transform mediated by piezoelectrically coupled nanoscale resonators. Our technique allows sensitive, linear, and real-time measurement of electrical potentials from conceivably any voltage-sensitive device. With this method, we demonstrate the direct transduction of neuronal action potentials from an extracellular microelectrode. This approach to wiring nanoscale devices could lead to minimally invasive implantable sensors with thousands of channels for in vivo neuronal recording, medical diagnostics, and electrochemical sensing

Measuring the flatness of focal plane for very large mosaic CCD camera

Large mosaic multiCCD camera is the key instrument for modern digital sky survey. DECam is an extremely red sensitive 520 Megapixel camera designed for the incoming Dark Energy Survey (DES). It is consist of sixty two 4k$\times$2k and twelve 2k x 2k 250-micron thick fully-depleted CCDs, with a focal plane of 44 cm in diameter and a field of view of 2.2 square degree. It will be attached to the Blanco 4-meter telescope at CTIO. The DES will cover 5000 square-degrees of the southern galactic cap in 5 color bands (g, r, i, z, Y) in 5 years starting from 2011. To achieve the science goal of constraining the Dark Energy evolution, stringent requirements are laid down for the design of DECam. Among them, the flatness of the focal plane needs to be controlled within a 60-micron envelope in order to achieve the specified PSF variation limit. It is very challenging to measure the flatness of the focal plane to such precision when it is placed in a high vacuum dewar at 173 K. We developed two image based techniques to measure the flatness of the focal plane. By imaging a regular grid of dots on the focal plane, the CCD offset along the optical axis is converted to the variation the grid spacings at different positions on the focal plane. After extracting the patterns and comparing the change in spacings, we can measure the flatness to high precision. In method 1, the regular dots are kept in high sub micron precision and cover the whole focal plane. In method 2, no high precision for the grid is required. Instead, we use a precise XY stage moves the pattern across the whole focal plane and comparing the variations of the spacing when it is imaged by different CCDs. Simulation and real measurements show that the two methods work very well for our purpose, and are in good agreement with the direct optical measurements.Comment: Presented at SPIE Conference,Ground-based and Airborne Instrumentation for Astronomy III, San Diego, 201

High-resolution three-dimensional extracellular recording of neuronal activity with microfabricated electrode arrays

Microelectrode array recordings of neuronal activity present significant opportunities for studying the brain with single-cell and spike-time precision. However, challenges in device manufacturing constrain dense multisite recordings to two spatial dimensions, whereas access to the three-dimensional (3D) structure of many brain regions appears to remain a challenge. To overcome this limitation, we present two novel recording modalities of silicon-based devices aimed at establishing 3D functionality. First, we fabricated a dual-side electrode array by patterning recording sites on both the front and back of an implantable microstructure. We found that the majority of single-unit spikes could not be simultaneously detected from both sides, suggesting that in addition to providing higher spatial resolution measurements than that of single-side devices, dual-side arrays also lead to increased recording yield. Second, we obtained recordings along three principal directions with a multilayer array and demonstrated 3D spike source localization within the enclosed measurement space. The large-scale integration of such dual-side and multilayer arrays is expected to provide massively parallel recording capabilities in the brain

Self-sampling tools to increase cancer screening among underserved patients: A pilot randomized controlled trial

BACKGROUND: Screening can reduce cancer mortality, but uptake is suboptimal and characterized by disparities. Home-based self-sampling can facilitate screening for colorectal cancer (with stool tests, eg, fecal immunochemical tests) and for cervical cancer (with self-collected human papillomavirus tests), especially among patients who face barriers to accessing health care. Additional data are needed on feasibility and potential effects of self-sampling tools for cancer screening among underserved patients. METHODS: We conducted a pilot randomized controlled trial with patients (female, ages 50-65 years, out of date with colorectal and cervical cancer screening) recruited from federally qualified health centers in rural and racially segregated counties in Pennsylvania. Participants in the standard-of-care arm (n = 24) received screening reminder letters. Participants in the self-sampling arm (n = 24) received self-sampling tools for fecal immunochemical tests and human papillomavirus testing. We assessed uptake of screening (10-week follow-up), self-sampling screening outcomes, and psychosocial variables. Analyses used Fisher exact tests to assess the effect of study arm on outcomes. RESULTS: Cancer screening was higher in the self-sampling arm than the standard-of-care arm (colorectal: 75% vs 13%, respectively, odds ratio = 31.32, 95% confidence interval = 5.20 to 289.33; cervical: 79% vs 8%, odds ratio = 72.03, 95% confidence interval = 9.15 to 1141.41). Among participants who returned the self-sampling tools, the prevalence of abnormal findings was 24% for colorectal and 18% for cervical cancer screening. Cancer screening knowledge was positively associated with uptake (P \u3c .05). CONCLUSIONS: Self-sampling tools can increase colorectal and cervical cancer screening among unscreened, underserved patients. Increasing the use of self-sampling tools can improve primary care and cancer detection among underserved patients. CLINICAL TRIALS REGISTRATION NUMBER: STUDY00015480

Detection of xenoestrogens in serum after immunoprecipitation of endogenous steroidal estrogens.

In this article we report a simple and efficient method for detecting nonsteroidal estrogens in a biologic sample. This method uses polyclonal antibodies to estradiol (E2) to immunoprecipitate these major biologically active steroidal estrogens, leaving behind the nonsteroidal estrogens, which are then detected in a cell-based transcriptional activation bioassay for estrogen receptor agonist. The immunoprecipitation method efficiently removed 99% of radiolabeled E2 and estrone (E1) from human serum. In experiments in which supraphysiologic concentrations of E2 and E1 to human serum, all of the immunoreactive estrogens were still removed by the immunoprecipitation protocol. We carried out an in vivo validation study of this method in which we treated female macaques with the xenoestrogen nonylphenol (NP), during the late follicular phase of the menstrual cycle. We used blood samples collected before and after treatment to evaluate and characterize endogenous and exogenous serum estrogens. An immunoassay for E2 did not detect the NP in treated monkeys. The cell-based bioassay also did not detect the estrogenic activity of NP because of its saturation by the endogenous serum steroidal estrogens. However, when steroidal estrogens were removed by immunoprecipitation, we detected the estrogenic activity of NP in the bioassay. Thus, this approach is appropriate for detecting exogenous, nonsteroidal estrogens in serum samples

Bone resorption is affected by follicular phase length in female rotating shift workers.

Stressors as subtle as night work or shift work can lead to irregular menstrual cycles, and changes in reproductive hormone profiles can adversely affect bone health. This study was conducted to determine if stresses associated with the disruption of regular work schedule can induce alterations in ovarian function which, in turn, are associated with transient bone resorption. Urine samples from 12 rotating shift workers from a textile mill in Anqing, China, were collected in 1996-1998 during pairs of sequential menstrual cycles, of which one was longer than the other (28.4 vs. 37.4 days). Longer cycles were characterized by a prolonged follicular phase. Work schedules during the luteal-follicular phase transition (LFPT) preceding each of the two cycles were evaluated. All but one of the shorter cycles were associated with regular, forward phase work shift progression during the preceding LFPT. In contrast, five longer cycles were preceded by a work shift interrupted either by an irregular shift or a number of "off days." Urinary follicle-stimulating hormone levels were reduced in the LFPT preceding longer cycles compared with those in the LFPT preceding shorter cycles. There was greater bone resorption in the follicular phase of longer cycles than in that of shorter cycles, as measured by urinary deoxypyridinoline. These data confirm reports that changes in work shift can lead to irregularity in menstrual cycle length. In addition, these data indicate that there may be an association between accelerated bone resorption in menstrual cycles and changes of regularity in work schedule during the preceding LFPT

Multiplexed, High Density Electrophysiology with Nanofabricated Neural Probes

Extracellular electrode arrays can reveal the neuronal network correlates of behavior with single-cell, single-spike, and sub-millisecond resolution. However, implantable electrodes are inherently invasive, and efforts to scale up the number and density of recording sites must compromise on device size in order to connect the electrodes. Here, we report on silicon-based neural probes employing nanofabricated, high-density electrical leads. Furthermore, we address the challenge of reading out multichannel data with an application-specific integrated circuit (ASIC) performing signal amplification, band-pass filtering, and multiplexing functions. We demonstrate high spatial resolution extracellular measurements with a fully integrated, low noise 64-channel system weighing just 330 mg. The on-chip multiplexers make possible recordings with substantially fewer external wires than the number of input channels. By combining nanofabricated probes with ASICs we have implemented a system for performing large-scale, high-density electrophysiology in small, freely behaving animals that is both minimally invasive and highly scalable