A blended neurostimulation protocol to delineate cortico-muscular and spino-muscular dynamics following neuroplastic adaptation.

In this paper we propose a novel neurostimulation protocol that provides an intervention-based assessment to distinguish the contributions of different motor control networks in the cortico-spinal system. Specifically, we use a combination of non-invasive brain stimulation and neuromuscular stimulation to probe neuromuscular system behavior with targeted impulse-response system identification. In this protocol, we use an in-house developed human-machine interface (HMI) for an isotonic wrist movement task, where the user controls a cursor on-screen. During the task, we generate unique motor evoked potentials based on triggered cortical or spinal level perturbations. Externally applied brain-level perturbations are triggered through TMS to cause wrist flexion/extension during the volitional task. The resultant contraction output and related reflex responses are measured by the HMI. These movements also include neuromodulation in the excitability of the brain-muscle pathway via transcranial direct current stimulation. Colloquially, spinal-level perturbations are triggered through skin-surface neuromuscular stimulation of the wrist muscles. The resultant brain-muscle and spinal-muscle pathways perturbed by the TMS and NMES, respectively, demonstrate temporal and spatial differences as manifested through the human-machine interface. This then provides a template to measure the specific neural outcomes of the movement tasks, and in decoding differences in the contribution of cortical- (long-latency) and spinal-level (short-latency) motor control. This protocol is part of the development of a diagnostic tool that can be used to better understand how interaction between cortical and spinal motor centers changes with learning, or injury such as that experienced following stroke.

Development of a Human Infant Feeding Reinforcement System.

We present a custom-made device that enables the study of food reinforcement in infants younger than nine months. This device called INFERS (INfant FEeding Reinforcement System) consists of a smart feeding controller and milk delivery components which has been constructed using custom and off-the-shelf components. Testing on three infants to date shows that INFERS functions properly and enables us to collect data on infant feeding activity and correlate this with the amount of effort infants must expend to get the milk.

Strengthening the Role of Nurses in Medical Device Development.

UNLABELLED: Medical devices and innovative technology promise to revolutionize health care. Despite the importance of involving nurses in the collaborative medical device development processes, there are few learning opportunities in nursing programs. The purpose of this article is to provide a conceptual guide for nurse educators and researchers to engage nursing expertise in medical device development processes. METHOD: A review of the literature guided the creation of the "Strengthening the Role of Nurses in Medical Device Development Roadmap" model. The model was used to describe how nurses can be engaged in multidisciplinary design of medical devices. An academic transdisciplinary team piloted the application of the model. RESULTS: The model includes the stages of needs assessment, planned brainstorm, feasibility determination, concept design, and prototype building. A transdisciplinary team case study of improving an asthma home-monitoring devices illustrates effective application of the model. CONCLUSION: Nurse leaders in the academic setting can effectively use the "Strengthening the Role of Nurses in Medical Device Development Roadmap" to inform their engagement of nurses in early medical device development and innovation processes.

A Review of Worldwide Patents: Innovations in Peak Flow Meters for Asthma.

BACKGROUND: Contemporary healthcare nurses increasingly rely on innovative technology for assessment, treatment, and patient self-management. Funding opportunities as well are increasingly steering toward technology development and innovation. Health researchers, including nursing scientists, who are engaged in medical device innovation need to assess the state of the art of current technology. This requires an intellectual property analysis, or patent search, which is not covered by the types of literature reviews customarily used in health science research. PURPOSE: The purposes of this article are to illustrate a methodical review of worldwide patents and to show how those results can be used to identify possible products available for use. APPROACH: An application of peak flow meters for use by patients with asthma is used to illustrate the process. The Derwent Innovations Index interface with keyword searching is illustrated, as is the use of Google Patents. From the 14 patent document results, six possible technologies were identified. The patent search revealed innovations in asthma peak flow meters for use in future research and identified future directions for device development. DISCUSSION: These results support the claim that patent literature must be included in reviews that seek to identify technology state-of-the-art healthcare applications and that advances in the nursing research paradigm should include patents as background and scholarly products.

Ratiometric, filter-free optical sensor based on a complementary metal oxide semiconductor buried double junction photodiode.

We report a complementary metal oxide semiconductor integrated circuit (CMOS IC) with a buried double junction (BDJ) photodiode that (i) provides a real-time output signal that is related to the intensity ratio at two emission wavelengths and (ii) simultaneously eliminates the need for an optical filter to block Rayleigh scatter. We demonstrate the BDJ platform performance for gaseous NH3 and aqueous pH detection. We also compare the BDJ performance to parallel results obtained by using a slew scanned fluorimeter (SSF). The BDJ results are functionally equivalent to the SSF results without the need for any wavelength filtering or monochromators and the BDJ platform is not prone to errors associated with source intensity fluctuations or sensor signal drift.

Creating diversified response profiles from a single quenchometric sensor element by using phase-resolved luminescence.

We report a new strategy for generating a continuum of response profiles from a single luminescence-based sensor element by using phase-resolved detection. This strategy yields reliable responses that depend in a predictable manner on changes in the luminescent reporter lifetime in the presence of the target analyte, the excitation modulation frequency, and the detector (lock-in amplifier) phase angle. In the traditional steady-state mode, the sensor that we evaluate exhibits a linear, positive going response to changes in the target analyte concentration. Under phase-resolved conditions the analyte-dependent response profiles: (i) can become highly non-linear; (ii) yield negative going responses; (iii) can be biphasic; and (iv) can exhibit super sensitivity (e.g., sensitivities up to 300 fold greater in comparison to steady-state conditions).

Micro-fabricated DC comparison calorimeter for RF power measurement.

Diode detection and bolometric detection have been widely used to measure radio frequency (RF) power. However, flow calorimeters, in particular micro-fabricated flow calorimeters, have been mostly unexplored as power meters. This paper presents the design, micro-fabrication and characterization of a flow calorimeter. This novel device is capable of measuring power from 100 µW to 200 mW. It has a 50-Ohm load that is heated by the RF source, and the heat is transferred to fluid in a microchannel. The temperature change in the fluid is measured by a thermistor that is connected in one leg of a Wheatstone bridge. The output voltage change of the bridge corresponds to the RF power applied to the load. The microfabricated device measures 25.4 mm × 50.8 mm, excluding the power supplies, microcontroller and fluid pump. Experiments demonstrate that the micro-fabricated sensor has a sensitivity up to 22 × 10⁻³ V/W. The typical resolution of this micro-calorimeter is on the order of 50 µW, and the best resolution is around 10 µW. The effective efficiency is 99.9% from 0−1 GHz and more than 97.5% at frequencies up to 4 GHz. The measured reflection coefficient of the 50-Ohm load and coplanar wave guide is less than −25 dB from 0−2 GHz and less than −16 dB at 2−4 GHz.

Filterless optical oxygen sensor based on a CMOS buried double junction photodiode.

We present a custom CMOS IC with a buried double junction (BDJ) photodiode to detect and process the optical signal, eliminating the need for any off-chip optical filters. The on-chip signal processing circuitry improves the desired signal extraction from the optical background noise. Since the IC is manufactured using standard commercial fabrication processes with no post-processing necessary, the system can ultimately be low cost to fabricate. Additionally, because of the CMOS integration, it will consume little power when operating, and even less during stand-by.

Image geometric corrections for a new EMCCD-based dual modular x-ray imager.

An EMCCD-based dual modular x-ray imager was recently designed and developed from the component level, providing a high dynamic range of 53 dB and an effective pixel size of 26 µm for angiography and fluoroscopy. The unique 2 × 1 array design efficiently increased the clinical field of view, and also can be readily expanded to an MxN array implementation. Due to the alignment mismatches between the EMCCD sensors and the fiber optic tapers in each module, the output images or video sequences result in a misaligned 2048 × 1024 digital display if uncorrected. In this paper, we present a method for correcting display registration using a custom-designed two layer printed circuit board. This board was designed with grid lines to serve as the calibration pattern, and provides an accurate reference and sufficient contrast to enable proper display registration. Results show an accurate and fine stitching of the two outputs from the two modules.

Optical Demonstration of a Medical Imaging System with an EMCCD-Sensor Array for Use in a High Resolution Dynamic X-ray Imager.

Use of an extensible array of Electron Multiplying CCDs (EMCCDs) in medical x-ray imager applications was demonstrated for the first time. The large variable electronic-gain (up to 2000) and small pixel size of EMCCDs provide effective suppression of readout noise compared to signal, as well as high resolution, enabling the development of an x-ray detector with far superior performance compared to conventional x-ray image intensifiers and flat panel detectors. We are developing arrays of EMCCDs to overcome their limited field of view (FOV). In this work we report on an array of two EMCCD sensors running simultaneously at a high frame rate and optically focused on a mammogram film showing calcified ducts. The work was conducted on an optical table with a pulsed LED bar used to provide a uniform diffuse light onto the film to simulate x-ray projection images. The system can be selected to run at up to 17.5 frames per second or even higher frame rate with binning. Integration time for the sensors can be adjusted from 1 ms to 1000 ms. Twelve-bit correlated double sampling AD converters were used to digitize the images, which were acquired by a National Instruments dual-channel Camera Link PC board in real time. A user-friendly interface was programmed using LabVIEW to save and display 2K × 1K pixel matrix digital images. The demonstration tiles a 2 × 1 array to acquire increased-FOV stationary images taken at different gains and fluoroscopic-like videos recorded by scanning the mammogram simultaneously with both sensors. The results show high resolution and high dynamic range images stitched together with minimal adjustments needed. The EMCCD array design allows for expansion to an M×N array for arbitrarily larger FOV, yet with high resolution and large dynamic range maintained.

Component Level Modular Design of a Solid State X-ray Image Intensifier for an M×N Array.

The Solid-State X-ray Image Intensifier (SSXII) is a novel dynamic x-ray imager, based on an array of electron-multiplying CCDs (EMCCDs), that can significantly improve performance compared to conventional x-ray image intensifiers (XIIs) and flat panel detectors (FPDs). To expand the field-of-view (FOV) of the SSXII detectors while maintaining high resolution, a scalable component level modular design is presented. Each module can be fit together with minimum dead-space and optically coupled to one contiguous x-ray converter plate. The electronics of each of the modules consists of a detachable head-board, on which is mounted the EMCCD, and a driver board. The size of the head-boards is minimized to ensure that the modules fit together properly. The driver boards connect with the head-boards via flat cables and are designed to be plugged into the main mother-board that contains an FPGA chip that generates the driving clock signals for the EMCCDs and analog-to-digital converter (ADC). At the front-end, a high speed ADC on each of the driver boards samples and digitizes the EMCCD analog output signal and an extensible modular digital multiplexer back-end is used to acquire and combine image data from multiple modules. The combined digital data is then transmitted to a PC via a standard Camera Link interface. Eventually, this modular design will be extended to a 3×3 or larger array to accomplish full clinical FOVs and enable the SSXII to replace conventional lower-resolution XIIs or FPDs.

Quantum Performance Analysis of an EMCCD-based X-ray Detector Using Photon Transfer Technique.

The low electronic noise, high resolution, and good temporal performance of electron-multiplying CCDs (EMCCDs) are ideally suited for applications traditionally served by x-ray image intensifiers. In order to improve an expandable clinical detector's field-of-view and have full control of the system performance, we have successfully built a solid-state x-ray detector. The photon transfer technique was used to quantify the EMCCD quantum performance in terms of sensitivity (or camera gain constant, K), read noise (RN), full-well capacity (FW), and dynamic range (DR). Measured results show the system maintains a K of 11.3 ± 0.9 e(-)/DN at unit gain, with a read noise of 71.5±6.0 e(-)rms at gain 1, which decreases proportionally with higher gains. The full well capacity was measured to be 31.3±2.7 ke(-), providing a dynamic range of 52.8±0.7 dB using the chip manufacturer specified clocking scheme. Similar performance was measured with other commercial camera systems. The manufacturer data sheet indicates a dynamic range of 66 dB is plausible with improved read noise and full well capacity. Different clocking schemes are under investigation to assess their impact on improving performance towards idealized values. EMCCD driver clock voltage levels were adjusted individually to check the influence on quantum performance. The clocks work to transfer charge from the image area to readout amplifier through the storage area, horizontal and multiplication registers. Results indicate that the clock that contributes to lateral overflow drain bias is essential to the system performance in terms of dynamic range and full well capacity. The serial register clocks used for transporting charge stored in the pixels of the memory lines to the output amplifier had the largest effect on RN, while others had less of an impact. Initial adjustment of these clocks resulted in a variability of 16% in the performance of dynamic range, 38% in read noise and 56% in full well capacity. Quantifying the quantum performance provides valuable insight into overall performance and enables optimal adjustment of the clocking scheme. Further improvements are expected.

Tailored xerogel-based sensor arrays and artificial neural networks yield improved O2 detection accuracy and precision.

The objective of this research is to develop arrays of tuned chemical sensors wherein each sensor element responds to a particular target analyte in a unique manner. By creating sol-gel-derived xerogels that are co-doped with two luminophores at a range of molar ratios, we can form suites of sensor elements that can exhibit a continuum of response profiles. We trained an artificial neural network (ANN) to "learn" to identify the optical outputs from these xerogel-based sensor arrays. By using the ANN in concert with our tailored sensor arrays we obtained a 5-10 fold improvement in accuracy and precision for quantifying O2 in unknown samples. We also explored the response characteristics of these types of sensor elements after they had been contacted with rat plasma/blood. Contact with plasma/blood caused approximately 15% of the luminophore molecules within the xerogels to become non-responsive to O2. This behavior is consistent with rat albumin blocking certain pore sub-populations within the mesoporous xerogel matrix thereby limiting O2 access to the luminophores.

O(2)-responsive chemical sensors based on hybrid xerogels that contain fluorinated precursors.

We report the development and analytical figures of merit associated with several new O(2)-responsive sensor materials. These new sensing materials are formed by sequestering the luminophore tris(4,7-diphenyl-1,10-phenanthroline)ruthenium(II) ([Ru(dpp)(3)](2+)) within hybrid xerogels that are composed of two of the following methoxysilanes: tetramethoxysilane, n-propyl-trimethoxysilane, 3,3,3-trifluoropropyl-trimethoxysilane, phenethyl-trimethoxysilane, and pentafluorophenylpropyl-trimethoxysilane. Steady-state and time-resolved luminescence measurements are used to investigate these hybrid xerogel-based sensor materials and elucidate the underlying reasons for the observed performance. The results show that many of the [Ru(dpp)(3)](2+)-doped composites form visually uniform, crack-free xerogel films that can be used to construct O(2) sensors that have linear calibration curves and excellent long-term stability. To the best of our knowledge, the [Ru(dpp)(3)](2+)-doped fluorinated hybrid xerogels also exhibit the highest O(2) sensitivity of any reported [Ru(dpp)(3)](2+)-based sensor platform.

An analog VLSI chip emulating polarization vision of Octopus retina.

Biological systems provide a wealth of information which form the basis for human-made artificial systems. In this work, the visual system of Octopus is investigated and its polarization sensitivity mimicked. While in actual Octopus retina, polarization vision is mainly based on the orthogonal arrangement of its photoreceptors, our implementation uses a birefringent micropolarizer made of YVO4 and mounted on a CMOS chip with neuromorphic circuitry to process linearly polarized light. Arranged in an 8 x 5 array with two photodiodes per pixel, each consuming typically 10 microW, this circuitry mimics both the functionality of individual Octopus retina cells by computing the state of polarization and the interconnection of these cells through a bias-controllable resistive network.

Templated xerogels as platforms for biomolecule-less biomolecule sensors.

We report on a new sensor strategy that we have termed protein imprinted xerogels with integrated emission sites (PIXIES). The PIXIES platform is completely self-contained, and it achieves analyte recognition without a biorecognition element (e.g., antibody). The PIXIES relies upon sol-gel-derived xerogels, molecular imprinting, and the selective installation of a luminescent reporter molecule directly within the molecularly imprint site. In operation the templated xerogel selectively recognizes the target analyte, the analyte binds to the template site, and binding causes a change in the physicochemical properties within the template site that are sensed and reported by the luminescent probe molecule. We report the PIXIES analytical figures of merit for and compare these results to a standard ELISA. For human interleukin-1 the PIXIES-based sensor elements exhibited the following analytical figures of merit: (i) approximately 2 pg/mL detection limits; (ii) <2 min response times; (iii) >85 selectivity; (iv) <6% R.S.D. long term drift over 16 weeks of ambient storage; (v) >95% reversibility after more than 25 cycles; and (vi) >85% recoveries on spiked samples.

Multilevel category structure in the ART-2 network.

Multilevel categorization is investigated within the context of analog activity patterns on the output layer of an ART 2 network. The ART 2 network parameters are analyzed in terms of stable category formation and in terms of the number of nodes in the output layer that can become most active. The resulting activity patterns on the output layer demonstrate a multilevel category structure based on the relative differences between patterns that exist for many different values of the vigilance parameter. We have shown that the information contained in the output analog patterns can be interpreted in several different ways, which is not possible when the category is represented by a single winning node. Also, favorable comparisons are also demonstrated between the category structure emerging from the set of category patterns and principles of categorization in psychology and neurobiology.