Breaking Barriers: Exploring Neurotransmitters through In Vivo vs. In Vitro Rivalry.

Neurotransmitter analysis plays a pivotal role in diagnosing and managing neurodegenerative diseases, often characterized by disturbances in neurotransmitter systems. However, prevailing methods for quantifying neurotransmitters involve invasive procedures or require bulky imaging equipment, therefore restricting accessibility and posing potential risks to patients. The innovation of compact, in vivo instruments for neurotransmission analysis holds the potential to reshape disease management. This innovation can facilitate non-invasive and uninterrupted monitoring of neurotransmitter levels and their activity. Recent strides in microfabrication have led to the emergence of diminutive instruments that also find applicability in in vitro investigations. By harnessing the synergistic potential of microfluidics, micro-optics, and microelectronics, this nascent realm of research holds substantial promise. This review offers an overarching view of the current neurotransmitter sensing techniques, the advances towards in vitro microsensors tailored for monitoring neurotransmission, and the state-of-the-art fabrication techniques that can be used to fabricate those microsensors.

XRF online analyzer for measurements of P2O5 content in phosphate slurry.

Online X-ray Fluorescence (XRF) setup was constructed and optimized for analysing the P2O5 content in phosphate slurry (PS). Serval samples were analysed using two configurations of the setup, one with low and vertical flow and another with high and horizontal flow. The mean absolute error achieved through the first configuration was 0.87% and 0.38% using the second configuration. Reference samples were analyzed using the two configurations to construct the calibration curves. The curves cover a concentration range of P2O5 from 13.50 to 18.50% when considering the horizontal flow configuration, and a range of 14.00-15.60% when considering the vertical flow setup. An experimental study was conducted in order to optimize the measurement parameters for the online measurement of P2O5 in the phosphate slurry using the horizontal flow setup. A good signal-to-noise ratio (SNR) of [Formula: see text] was attained using an excitation energy of 20 kV or 25 kV, an excitation current of 600 µA, a distance of 18 mm between the sample and the detector, a measurement time of 60 s per spectrum and the use of an Aluminum filter between the X-ray tube and the measurement window. Online X-ray fluorescence analysis of P entails some challenges due to the low characteristic energy of P, the phosphate slurry matrix and the online analysis mode. However, the outcomes of this study indicate that XRF is a promising technology to meet the requirement for digitalization of chemical analysis of phosphate products.

The effect of particle size and water content on XRF measurements of phosphate slurry.

Phosphate slurries are studied using the XRF technique and the effect of the particle sizes and the water content parameters are analyzed and reported for the first time. Samples of the phosphate slurry with different particle sizes (425 µm, 300 µm, 250 µm, 200 µm, 160 µm and 106 µm) and different water contents (30%, 40%, 50%, 60%) were analyzed using an energy-dispersive X-ray spectrometer (EDXRF). The results show that the relative error of measurement varies with the particle size of the analyzed sample, the water content and the element measured. The relative error increases with the increase of the particle size for the compounds P2O5, Al2O3, K2O, Cr2O3, Fe2O3 and Sr. The ratio between the relative errors related to the maximum and minimum grain sizes was 1.50 for P2O5, 4.01 for Al2O3, 15.58 for K2O, 1.22 for Cr2O3, 1.51 for Fe2O3 and 1.11 for Sr. Alternatively, an opposite evolution has been observed in the case of compounds CaO and SiO2. The relative error increases with increasing water content for all compounds existing in the slurry. Depending on the measured compound, the relative error increases by a factor that varies between 1.39 and 2.39. In the case of P2O5, the results do not show a clear correlation between the measurement error and the water content. A study will be conducted to investigate the effect of particle size and water content on XRF measurements in the case of phosphate slurry, aiming to develop an online XRF analyzer system for phosphate slurry.

Towards an advanced neurotechnological system: colorimetric sensing with a novel grism-based spectrometer, functionalized gold nanoparticles and a heterogeneous embedded system.

Neurotransmitter sensing in the brain is crucial for the understanding of neuro-degenerative diseases. Most modern methods for the purpose rely on bulky instruments or are disruptive to the neurotransmitter medium. In this work, we describe and evaluate the design of a novel, compact and non-invasive instrument for neurotransmitter detection based on the colorimetric sensing method. The instrument includes a grism-based spectrometer that measures the wavelength shift of gold nanoparticles that are functionalized with aptamers to act as neurotransmitter-specific markers. It also includes microfluidic and electronic subsystems for sample preparation and control, and processing of the obtained signal. The instrument is tested with gold nanoparticles and its performance is compared to that of a commercial instrument, showing that the designed prototype matches the commercial instrument in performance while being much smaller, and it can surpass it with further improvements. This article is part of the theme issue 'Advanced neurotechnologies: translating innovation for health and well-being'.

Wearable Sensor Based on Flexible Sinusoidal Antenna for Strain Sensing Applications.

A flexible sinusoidal-shaped antenna sensor is introduced in this work, which is a modified half-wave dipole that can be used for strain sensing applications. The presented antenna is an improved extension of the previously introduced antenna sensor for respiration monitoring. The electrical and radiative characteristics of the sinusoidal antenna and the effects of the geometrical factors are studied. An approach is provided for designing the antenna, and equations are introduced to estimate the geometrical parameters based on desired electrical specifications. It is shown that the antenna sensor can be designed to have up to 5.5 times more sensitivity compared to the last generation of the antenna sensor previously introduced for respiration monitoring. The conductive polymer material used to fabricate the new antenna makes it more flexible and durable compared to the previous generation of antenna sensors made of glass-based material. Finally, a reference antenna made of copper and an antenna sensor made of the conductive polymer are fabricated, and their electrical characteristics are analyzed in free space and over the body.

Microscope-FTIR Spectrometry Based Sensor for Neurotransmitters Detection.

In this work, we present a new sensing approach for aqueous samples based on the microscope-FTIR spectrometer and applied for neurotransmitters. Our contribution in this work consists of a new sample handling system for the microscope-FTIR spectrometer based on a total reflective mirror, a heated hydrophobic layer for solvent removal/evaporation and sample confinement and a microfluidic system that handles sample injection unlike standard sample handling system which was based only on a total reflective mirror. In addition, another part of our contribution consists of proposing a new algorithm to extract molecular composition of the solution with high estimation ratios and based on the analysis of detected peaks on IR spectra. The data acquired from the microscope-FTIR spectrometer was analyzed by a newly developed algorithm to identify each neurotransmitter in homogeneous and non-homogeneous solutions with high selectivity. We used six neurotransmitter molecules (Dopamine hydrochloride, L-Ascorbic acid, Acetylcholine chloride, y-Aminobutyric, Glycine and L-Glutamic acid). The results obtained based on the algorithm developed showed that, using the new system, the six neurotransmitters can be identified in homogeneous and mixture solutions with an estimation ratio range of 88.8%-100% for Dopamine hydrochloride, 80%-100% for L-Ascorbic acid, 75%-100% for Acetylcholine chloride, 75%-100% for L-Glutamic, 77.7%-100% for y-Aminobutyric and 75%-100% for Glycine.

A Compact Visible Light Spectrometer for Molecular Detection with Spherical Gold Nanoparticles.

Spectrometers are widely used in molecular detection. However most of them are bulky, power consuming, and quite expensive. This work presents the prototype of a compact visible spectrometer alternative that is battery-operated, and designed for autonomous operation and quick spectrum detection. It targets spherical gold nanoparticles spectroscopy, but other applications are possible thanks to a high-precision mechanism to move the sensor, which allows the spectrometer to cover a broad range of wavelengths in the visible spectrum.

Pseudo-Continuous Flow FTIR System for Glucose, Fructose and Sucrose Identification in Mid-IR Range.

In this paper, we present a new FTIR-based microfluidic system for Glucose, Fructose and Sucrose detection. The proposed microfluidic system is based on a pseudo-continuous flow coupled to a microscope-FTIR instrument. The detection and characterization of sugar samples were performed by recording their absorption spectrum in the wavelength range 700⁻1000 cm - 1 of the Mid-IR region. The proposed pseudo-continuous flow system is designed to improve the uniformity of the sample distribution in the analyzed area versus conventional systems. The obtained results for different sugars concentrations, show a very low measurement error of 4.35% in the absorption peak intensity, which is ten times lower than the error obtained using the conventional measurements.

Microfluidic Spectrophotometer for Neurotransmitter Detection Based on Gold Nanoparticles: Preliminary Results.

A microfluidic-based spectrophotometer for neurotransmitters sensing is presented in this paper. In addition, a neurotransmitter photo-fingerprint is analyzed to evaluate the feasibility of selective neurotransmitter detection using optical techniques. The aim of this work is to detect major neurotransmitters (NTs) using a compact, portable and cost effective optical system for selective and real time NT concentration monitoring. Micro-spectroscopic detection of NTs is challenging because most of them are transparent to visible light. Nevertheless, they interfere with the absorption spectrum of gold nanoparticles (Au-NP), which exhibit maximum absorbance in the range of 520 nm. We observed an Au-NP maximum absorbance shift of up to 4nm in presence of NTs. Based on this shift, it is possible to detect NTs using visible ligh by using vertical-cavity surface-emitting laser (VCSEL) as light sources and an integrated system-on-chip (SoC) spectrophotometer.

A Portable Wireless Communication Platform Based on a Multi-Material Fiber Sensor for Real-Time Breath Detection.

In this paper, we present a new mobile wireless communication platform for real-time monitoring of an individual's breathing rate. The platform takes the form of a wearable stretching T-shirt featuring a sensor and a detection base station. The sensor is formed by a spiral-shaped antenna made from a multi-material fiber connected to a compact transmitter. Based on the resonance frequency of the antenna at approximately 2.4 GHz, the breathing sensor relies on its Bluetooth transmitter. The contactless and non-invasive sensor is designed without compromising the user's comfort. The sensing mechanism of the system is based on the detection of the signal amplitude transmitted wirelessly by the sensor, which is found to be sensitive to strain. We demonstrate the capability of the platform to detect the breathing rates of four male volunteers who are not in movement. The breathing pattern is obtained through the received signal strength indicator (RSSI) which is filtered and analyzed with home-made algorithms in the portable system. Numerical simulations of human breath are performed to support the experimental detection, and both results are in a good agreement. Slow, fast, regular, irregular, and shallow breathing types are successfully recorded within a frequency interval of 0.16-1.2 Hz, leading to a breathing rate varying from 10 to 72 breaths per minute.

Recent Advancements towards Full-System Microfluidics.

Microfluidics is quickly becoming a key technology in an expanding range of fields, such as medical sciences, biosensing, bioactuation, chemical synthesis, and more. This is helping its transformation from a promising R&D tool to commercially viable technology. Fuelling this expansion is the intensified focus on automation and enhanced functionality through integration of complex electrical control, mechanical properties, in situ sensing and flow control. Here we highlight recent contributions to the Sensors Special Issue series called "Microfluidics-Based Microsystem Integration Research" under the following categories: (i) Device fabrication to support complex functionality; (ii) New methods for flow control and mixing; (iii) Towards routine analysis and point of care applications; (iv) In situ characterization; and (v) Plug and play microfluidics.

Miniaturized FDDA and CMOS Based Potentiostat for Bio-Applications.

A novel fully differential difference CMOS potentiostat suitable for neurotransmitter sensing is presented. The described architecture relies on a fully differential difference amplifier (FDDA) circuit to detect a wide range of reduction-oxidation currents, while exhibiting low-power consumption and low-noise operation. This is made possible thanks to the fully differential feature of the FDDA, which allows to increase the source voltage swing without the need for additional dedicated circuitry. The FDDA also reduces the number of amplifiers and passive elements in the potentiostat design, which lowers the overall power consumption and noise. The proposed potentiostat was fabricated in 0.18 µm CMOS, with 1.8 V supply voltage. The device achieved 5 µA sensitivity and 0.99 linearity. The input-referred noise was 6.9 µV rms and the flicker noise was negligible. The total power consumption was under 55 µW. The complete system was assembled on a 20 mm × 20 mm platform that includes the potentiostat chip, the electrode terminals and an instrumentation amplifier for redox current buffering, once converted to a voltage by a series resistor. the chip dimensions were 1 mm × 0.5 mm and the other PCB components were off-chip resistors, capacitors and amplifiers for data acquisition. The system was successfully tested with ferricyanide, a stable electroactive compound, and validated with dopamine, a popular neurotransmitter.

Simple platform for chronic imaging of hippocampal activity during spontaneous behaviour in an awake mouse.

Chronic electrophysiological recordings of neuronal activity combined with two-photon Ca2+ imaging give access to high resolution and cellular specificity. In addition, awake drug-free experimentation is required for investigating the physiological mechanisms that operate in the brain. Here, we developed a simple head fixation platform, which allows simultaneous chronic imaging and electrophysiological recordings to be obtained from the hippocampus of awake mice. We performed quantitative analyses of spontaneous animal behaviour, the associated network states and the cellular activities in the dorsal hippocampus as well as estimated the brain stability limits to image dendritic processes and individual axonal boutons. Ca2+ imaging recordings revealed a relatively stereotyped hippocampal activity despite a high inter-animal and inter-day variability in the mouse behavior. In addition to quiet state and locomotion behavioural patterns, the platform allowed the reliable detection of walking steps and fine speed variations. The brain motion during locomotion was limited to ~1.8 µm, thus allowing for imaging of small sub-cellular structures to be performed in parallel with recordings of network and behavioural states. This simple device extends the drug-free experimentation in vivo, enabling high-stability optophysiological experiments with single-bouton resolution in the mouse awake brain.

Towards a Multifunctional Electrochemical Sensing and Niosome Generation Lab-on-Chip Platform Based on a Plug-and-Play Concept.

In this paper, we present a new modular lab on a chip design for multimodal neurotransmitter (NT) sensing and niosome generation based on a plug-and-play concept. This architecture is a first step toward an automated platform for an automated modulation of neurotransmitter concentration to understand and/or treat neurodegenerative diseases. A modular approach has been adopted in order to handle measurement or drug delivery or both measurement and drug delivery simultaneously. The system is composed of three fully independent modules: three-channel peristaltic micropumping system, a three-channel potentiostat and a multi-unit microfluidic system composed of pseudo-Y and cross-shape channels containing a miniature electrode array. The system was wirelessly controlled by a computer interface. The system is compact, with all the microfluidic and sensing components packaged in a 5 cm × 4 cm × 4 cm box. Applied to serotonin, a linear calibration curve down to 0.125 mM, with a limit of detection of 31 µ M was collected at unfunctionalized electrodes. Added sensitivity and selectivity was achieved by incorporating functionalized electrodes for dopamine sensing. Electrode functionalization was achieved with gold nanoparticles and using DNA and o-phenylene diamine polymer. The as-configured platform is demonstrated as a central component toward an "intelligent" drug delivery system based on a feedback loop to monitor drug delivery.

Electrochemical imaging for microfluidics: a full-system approach.

Electrochemistry is developed as a new chemical imaging modality for microfluidics. The technique is based on multipoint voltammetry using an embedded 20 × 10 miniature electrode array implemented on a customized printed circuit board. Electrode durability was enhanced by chemical modification of the electrode surfaces, which enabled continuous, stable use for over 2 months. A system-level approach enables automatic calibration, data acquisition and data processing through a graphical user interface. Following data processing, redox currents and peak positions are extracted from location-specific voltammograms and converted into pixels of an "electrochemical image". The system is validated by imaging steady-state and dynamic laminar flow patterns of flow-confined solutions of the redox pairs Fe(CN)6(3-/4-) or multi-redox environments that include coflowing Ru(NH3)6(2+/3+) solutions. The images obtained are compared with flow simulations and optical images for validation. A strategy to achieve measurements with spatial resolution smaller than the individual electrodes is also demonstrated as an avenue to enhance image spatial resolution. It is expected that this new approach to chemical imaging will expand the applicability of microfluidics in certain areas of chemistry and biology without requiring expertise in electrochemistry.

Towards a multi-wavelength spectroscopy platform for blood characterization and analysis.

Passing multiple light wavelengths through a blood sample makes it possible to investigate the presence and composition of cells, metabolytes and analytes such as blood cells, glucose, lactate and oxygen, providing valuable indications for diagnostic and health monitoring. In this paper, we present a test prototype of a multi-wavelength blood spectroscopy platform integrated with a microfluidic substrate to collect and convey blood samples through a series of micro-LEDs and a photo-detector. This spectroscopy platform is a proof of concept for a system that can collect absorbance and transmittance parameters of blood samples at several wavelengths within the visible and NIR spectrum, and transmit them wirelessly to a base station for real-time calculation and analysis. In-vitro measurements are performed with the proposed prototype with 5 channels covering wavelength from 400 nm to 940 nm A full characterization results of the proposed device are presented.

Automated and reconfigurable platform for niosome generation based on a microfluidic architecture.

Drug delivery at the nano-scale is becoming an important topic in nano and regenerative medicine as it can offer a very localized therapy. Therefore, niosomes are one of the most important vehicles to release drug at the nanoscale. In this paper, we present a new automated microsystem for niosome generation on-demand. Used niosome were based on a mixture of cholesterol and dicetyl phosphate with chloroform. Three compact micropumps are connected to a microfluidic substrate in order to generate 100 nm noisome vesicles. Through this paper we also investigated the impact of using 150 µm pseudo-Y and cross shape microchannel on the diameter of vesicles. We have observed reliable results with Y-shaped microchannel, which was able to generate vesicles down to 91 nm. All the system is based on a low-cost fabrication process using dry photo resist.

A wide range and high sensitivity four-channel compact electrochemical biosensor for neurotransmitter detection on a microfluidic platform.

We present a four-channel, high-sensitivity and linearity electrochemical biosensor for neurotransmitter (NT) detection and measurement. Using a multi-channel microfluidic platform makes this biosensor capable of detecting NT-related currents going from nanoamperes to milliamperes, with a sensitivity of the order of picoamperes. Moreover, by using a fully differential potentiostat architecture, the biosensor offers a high common-mode rejection ratio (90 dB), making it appropriate for low-noise and high-sensitive applications. The system was implemented on a 15 mm × 15 mm PCB with direct interface to the microfluidic chambers. It was calibrated with a 5 mM ferrocyanide solution and successfully tested with dopamine at three concentrations. The system shows a minimum sensistivity of 100 pA and consumes 60 mW.

Reconfigurable Prototyping Microfluidic Platform for DEP Manipulation and Capacitive Sensing.

In this paper, we present a new rapid prototyping platform dedicated to dielectrophoretic microfluidic manipulation and capacitive cell sensing. The proposed platform offers a reconfigurable design including 4 independently programmable output channels to be distributed across 64 electrodes. Although its range of frequency covers up to 3.4 MHz, signal amplitude accuracy ( +/-10%) was demonstrated for frequencies up to 1 MHz and channel-to-channel phase shift setting was stable up to 1.5 MHz. A test of maximum resistive load showed a 10% attenuation of a 12 V peak-to-peak signal with a 22 Ω load. The platform has an advanced capacitive sensor to measure capacitance variation between in-channel electrodes with a sampling frequency up to 5 kH z. Experimental data of capacitive sensor showed a sensitivity of 100 fF. The sensor can be extended to 4 parallel measurements with lower frequency. We also present a new assembly technique for reusable microfluidic chip based on anisotropic adhesive conductive film, epoxy and PDMS. The proposed platform provides a wide range of control signals depending on the type of manipulation as sine, rectangular or square wave. The frequency range is extendible up to 3.4 MHz, in addition to a programmable phase shift circuit with a minimum phase step of 3.6(°) for each signal.