Neural recordings made to date through various approaches-both in-vitro or in-vivo-lack high spatial resolution and a high signal-to-noise ratio (SNR) required for detailed understanding of brain ...function, synaptic plasticity, and dysfunction. These shortcomings in turn deter the ability to further design diagnostic, therapeutic strategies and the fabrication of neuro-modulatory devices with various feedback loop systems. We report here on the simulation and fabrication of fully configurable neural micro-electrodes that can be used for both in vitro and in vivo applications, with three-dimensional semi-insulated structures patterned onto custom, fine-pitch, high density arrays. These microelectrodes were interfaced with isolated brain slices as well as implanted in brains of freely behaving rats to demonstrate their ability to maintain a high SNR. Moreover, the electrodes enabled the detection of epileptiform events and high frequency oscillations in an epilepsy model thus offering a diagnostic potential for neurological disorders such as epilepsy. These microelectrodes provide unique opportunities to study brain activity under normal and various pathological conditions, both in-vivo and in in-vitro, thus furthering the ability to develop drug screening and neuromodulation systems that could accurately record and map the activity of large neural networks over an extended time period.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The electrothermal effect has been investigated extensively in microfluidics since the 1990s and has been suggested as a promising technique for fluid manipulations in lab-on-a-chip devices. The ...purpose of this article is to provide a timely overview of the previous works conducted in the AC electrothermal field to provide a comprehensive reference for researchers new to this field. First, electrokinetic phenomena are briefly introduced to show where the electrothermal effect stands, comparatively, versus other mechanisms. Then, recent advances in the electrothermal field are reviewed from different aspects and categorized to provide a better insight into the current state of the literature. Results and achievements of different studies are compared, and recommendations are made to help researchers weigh their options and decide on proper configuration and parameters.
Abstract
The purpose of this work is to demonstrate the fabrication process for cleanroom-free solid metal microneedles and perform quantification of insertion profiles. Metal microneedles were ...created using a modified wirebonding process and inserted into porcine tissue to determine design efficacy. Microneedle arrays were analyzed through optical imaging and scanning electron microscopy. Insertion forces were measured using combined uniaxial load cell and resistance measurement data. Microneedle arrays were successfully inserted into porcine tissue with high repeatability and reliability. These arrays demonstrate lower or equivalent insertion forces (less than 3 N) to other forms of microneedles in the literature without the need for complex cleanroom fabrication processes. The microneedle fabrication method presented here rapidly produces mass manufacturable, high-quality microneedle arrays with minimal insertion forces, able to reliably penetrate tissue samples. The manufacturing method presented here achieved array densities as high as 3200 needles cm
−2
. These microneedle arrays demonstrate simple fabrication of a reliable, high-density, pain-free drug delivery system, with potential applications in biosensing and electric field modulated drug delivery.
Electrothermal micropumps apply an AC electric field to a conductive fluid within the range of 10 kHz-1 MHz to generate fluid flow. In this frequency range, coulombic forces dominate fluid ...interactions over opposing dielectric forces, resulting in high flow rates (~50-100 μm/s). To date, the electrothermal effect-using asymmetrical electrodes-has been tested only with single-phase and 2-phase actuation, while dielectrophoretic micropumps have shown improved flow rates with 3- and 4-phase actuation. Simulating muti-phase signals in COMSOL Multiphysics requires additional modules and a more involved implementation to accurately represent the electrothermal effect in a micropump. Here, we report detailed simulations of the electrothermal effect under multi-phase conditions, including single-phase, 2-phase, 3-phase and 4-phase actuation patterns. These computational models indicate that 2-phase actuation leads to the highest flow rate, with 3-phase resulting in a 5% reduced flow rate and 4-phase resulting in an 11% reduced flow rate compared to 2-phase. With these modifications to the simulation, various actuation patterns can later be tested in COMSOL for a range of electrokinetic techniques.
Abstract Microneedles are a promising technology for pain-free and efficient pharmaceutical delivery. However, their clinical translation is currently limited by the absence of standardized testing ...methods for critical quality attributes (CQAs), such as mechanical robustness, which are essential for demonstrating safety and efficacy during regulatory review. A key aspect of mechanical robustness is transverse load capacity, which is currently assessed using diverse, non-standardized methods, which have limited capability to measure transverse failure forces at different heights along a microneedle. This is critical for understanding mechanics of potential failure modes during insertion after skin penetration. In this work we utilize a wire bond shear tester, a piece of test equipment widely used in the semiconductor industry, to measure the transverse load capacities of various microneedle designs. This approach is compatible with diverse microneedle types, geometries, and materials, and offers high-throughput and automated testing capabilities with high precision. We measure transverse failure loads with micron-scale control over the test height and have established comprehensive profiles of mechanical robustness along the length of different microneedle designs, which is a capability not previously demonstrated in literature for polymeric and metal microneedles. Transverse failure forces were 10 ± 0.3 gf–128 ± 12 gf for wire bonded gold and silver microneedles, 11 ± 0.7 gf–480 ± 69 gf for conical and pyramidal polymeric microneedles, and 206 ± 80 gf–381 ± 1 gf for 3D printed conical stainless steel microneedles. Additionally, we present standardized definitions for microneedle structural failure modes resulting from transverse loads, which can facilitate root cause failure analysis and defect detection during design and manufacturing, and aid in risk assessment of microneedle products. This work establishes a standardized approach to evaluating a significant CQA of microneedle products, which is a critical step towards expediting their clinical adoption.
Over 27 million individuals are affected every year worldwide with central nervous system (CNS) injuries. These injuries include but are not limited to traumatic brain injury (TBI) and spinal cord ...injury (SCI). CNS injuries remain a significant public health concern which demands reliable tools for rapid, on-sight, on-field, and point-of-care diagnostic (POC) solutions. To address these challenges, we developed a low-cost, open-source, hand-held, portable, and POC detection technology, termed as MicroDrop (μDrop), which can simultaneously detect up to eight target biomolecules and display results in both analog and digital formats. The data acquired is stored wirelessly in a cloud server for further investigation and statistical analysis. Multiplexing capability of μDrop and immuno-biosensors detects and quantifies Cleaved-Tau Protein (C-Tau) and Neuron-Filament (NFL) proteins in the blood of TBI patients. Immuno-biosensors rapidly sense the two target proteins in less than 30 min, with μDrop and a conventional potentiostat. C-Tau and NFL were selectively detected with μDrop within the dynamic range of 10 pg/mL - 100 ng/mL and the sensitivity range of 47 μA/pg mm2 - 65 μA/pg mm2. Comparing the biosensing performance with enzyme-linked immunosorbent assays (ELISA) shows that the immuno-biosensors combined with μDrop could successfully differentiate between clinical controls and injured patients.
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•The development of opensource multi-analyte portable electrochemical sensing device (μDrop).•μDrop performs differential pulse voltammetry mode of electrochemical sensing.•The comparable performance of μDrop to a commercial potentiostat.•Accurate detection of cleaved tau (C-Tau) and neuron filament light (NFL) in the blood of TBI patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Alternating Current Electrothermal (ACET) micropumps are a well-documented flow induction and mixing method. This phenomenon has significant promise as a reliable microfluidic pumping method for high ...conductivity biofluids, such as cerebrospinal fluid, urine, or blood. Practical implementations so far have been limited by complex designs focused on maximized flow rates, typically in only one direction at a time. This paper describes a device geometry demonstrating, and quantifying for the first time, fully reversible flow, that is, going from 100% flow in one direction to fully symmetrical 100% flow in the opposite direction. This design incorporates multiple features targeted at practical fabrication and applications. The design enables fine-tuning of flow speeds via adjustable signal strengths in a unique manner compared to traditional ACET devices. A full numerical simulation of this device has been performed within this work. Additionally, this paper reports several methods for increasing usability of ACET devices, including proposing coatings to prevent electrolysis and increase flow rates without the risk of fluid reactions, manufacturing methods for ease of handling, and specific device parameters for implementation in microdevices. The development of an ACET device that can precisely and efficiently pump and extract fluids allows for new applications in integrated biological systems and monitoring devices.
This paper describes 'didactical structures' as a possible outcome of research on teaching- leraning sequences. Starting from an explicit didactical perspective, in this case a so-called ...problem-posing approach, the research emphasis lies on the didactical qualitiy with which this particular perspective can be put into classroom practice in the teaching and learning of a certain topic. This is done by a process of developmental research, in which a research scenario, as a detailed prediction and theoretical justification of the hypothesized teaching/learning process, plays a crucial role. Three empirically supported resulting didactical structures are described, developed for the solution of different content dependent didactical problems. By reflection on these structures, more general structures and features are abstracted that enable transfer of the outcomes to the didactics of other topics. Finally, it is discussed what these results can offer to the development of a more general didactical theory.
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9.
An autonomous mobile system for the management of COPD van der Heijden, Maarten; Lucas, Peter J.F.; Lijnse, Bas ...
Journal of biomedical informatics,
June 2013, 2013-Jun, 2013-06-00, 20130601, Volume:
46, Issue:
3
Journal Article
Peer reviewed
Open access
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•The design of a novel mobile disease management system for COPD is described in detail.•Patient data is interpreted by a Bayesian network model for COPD-exacerbation detection.•The ...model is evaluated and shown to be able to reliably detect COPD exacerbations.•A pilot study with COPD patients has shown that the system is useful and usable.
Managing chronic disease through automated systems has the potential to both benefit the patient and reduce health-care costs. We have developed and evaluated a disease management system for patients with chronic obstructive pulmonary disease (COPD). Its aim is to predict and detect exacerbations and, through this, help patients self-manage their disease to prevent hospitalisation.
The carefully crafted intelligent system consists of a mobile device that is able to collect case-specific, subjective and objective, physiological data, and to alert the patient by a patient-specific interpretation of the data by means of probabilistic reasoning. Collected data are also sent to a central server for inspection by health-care professionals.
We evaluated the probabilistic model using cross-validation and ROC analyses on data from an earlier study and by an independent data set. Furthermore a pilot with actual COPD patients has been conducted to test technical feasibility and to obtain user feedback.
Model evaluation results show that we can reliably detect exacerbations. Pilot study results suggest that an intervention based on this system could be successful.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Presents the view that "developmental research" is needed in which small-scale curriculum development is cyclically coupled to in-depth classroom research of teaching-learning processes. Such ..."didactical" research methodology should result in worked-out examples of successful ways of teaching, according to new conceptual curriculum structures. (LZ)
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