The design, fabrication and characterization of a cost-efficient oceanographic instrument with microfabricated sensors for measuring conductivity, temperature and depth of seawater are presented. Conductivity and temperature sensors were fabricated using MEMS technology, which allows for customized small footprints and low production costs. Dedicated electronics for reading, processing and storing acquired sensor data are described. The developed instrument enables the measurement of seawater conductivity in a range from 4 mS/cm to 70 mS/cm. The conductivity measurement is temperature-compensated in the range from 2 °C to 40 °C, with an accuracy of ±0.1 mS/cm. The temperature sensor’s stability is 0.025 °C. The depth/pressure measurement range is up to 2000 m/200 bar, with a resolution of 0.1 bar. Temperature and conductivity sensor performance was assessed using laboratory equipment and designed electronics. The conductivity sensor was temperature-compensated to 0.01 mS/cm. The conductivity sensor electrode corrosion effect is presented below and was eliminated through adaptation of a signal acquisition circuit. Custom software was developed for monitoring critical conductivity sensor parameters (currents, voltages). A variation of 0.4% between cell conductance currents and voltages was established as a criterion for stable conductivity sensor operation.

A four-tether silicon microthermocycler for point-of-care PCR analytical systems is proposed. Substituting the commonly employed platinum with titanium in the fabrication of thin film resistance temperature detectors and heaters enabled the realization of a smaller device without compromising temperature accuracy or increasing heater lead power losses. The device was extensively analyzed through analytical modeling and FEM numerical simulations using a 3-D thermo-mechanical simulation model in COMSOL. Numerical simulations revealed that the four-tether design provides a 460% improvement in mechanical strength and a 57% reduction in the thermal time constant compared with a similar three-tether design, with a trade-off of a 22% increase in heat losses. Detailed structural and thermal analyses of crucial design parameters guided the optimization of the final geometry, leading to the successful fabrication of prototypes. It was shown that the current of 60 mA was sufficient to heat the fabricated solid and hollow silicon structure to 132 °C and 134 °C in 10 s for an applied heater power of 510 mW and 525 mW, respectively.

Abstract Thermal control devices such as thermal switches, thermal diodes, thermal regulators and thermal capacitors can control the intensity and direction of heat flow, which has proven useful in various thermal management applications. Their operation is analogous to that of their electrical counterparts, where temperature differences correspond to voltage differences and heat flow corresponds to electric current. Here we design and fabricate a thermal switch that controls the heat flow from the heat source by changing the thermal conductance when switching ON and OFF. The thermal switch uses electrostatic forces for actuation and makes thermal contact between the heat source and the heat sink when in the ON state, and breaks contact when in the OFF state. The thermal switch is constructed using the commercially available materials. The heat sink and heat source are made of silicon, and the active part of the heat switch is a flexible gadolinium sheet with a thickness of 161 µm. The proof-of-concept device was evaluated for a magnetocaloric application; however, the proposed thermal switch can be used in any thermal circuit for fast thermal regulation and advanced thermal control.

The development and characterization of a microfluidic electrochemical glucose biosensor are presented herein. The transducer part is based on thin-film metal electrodes on a glass substrate. The biological recognition element of the biosensor is the pyrroloquinoline quinone–glucose dehydrogenase (PQQ-GdhB) enzyme, selectively in situ immobilized via microcontact printing of a mixed self-assembling monolayer (SAM) on a gold working electrode, while the microfluidic part of the device comprises microchannel and microfluidic connections formed in a polydimethylsiloxane (PDMS) elastomer. The electrode properties throughout all steps of biosensor construction and the biosensor response to glucose concentration and analyte flow rate were characterized by cyclic voltammetry and chronoamperometry. A measurement range of up to 10 mM in glucose concentration with a linear range up to 200 μM was determined. A detection limit of 30 µM in glucose concentration was obtained. Respective biosensor sensitivities of 0.79 nA/µM/mm2 and 0.61 nA/µM/mm2 were estimated with and without a flow at 20 µL/min. The developed approach of in situ enzyme immobilization can find a wide number of applications in the development of microfluidic biosensors, offering a path towards continuous and time-independent detection.

The chapter will briefly present three distinctive concepts of the micropump actuator driving module, each with its waveform specifics and their impact on particular micropump performance (pumping media, flow rate and backpressure). First presented concept is based on two mutually-exclusive boost switched-mode power supply modules. Characterization of this module identified output voltage asymmetry to be the limiting factor of micropump performance. To assure driving symmetry, an alternative driving module, based on independent high-voltage stages and optocouplers, was implemented. This design is capable of driving a piezoelectric micropump with a rectangular waveform of programmable frequency, positive and negative amplitudes, slew rates and dead time. While this design provides maximum flow and backpressure characteristics, it does not offer minimal current consumption and long-term operation. To overcome this difficulty, our current design is based on an embedded arbitrary waveform generator, which offers an efficient trade-off between high pumping performance and low current consumption.

Microfluidics technologies have become a powerful tool in life science research laboratories over the past three decades. This review discusses three important segments of the field from origins and current status to future prospective: a) materials and microfabrication technologies from the field, b) research and development of essential microfluidic components and c) integration of components into complex microfluidic systems that will, according to some forecasts, play a key role in improving the quality of life for future generations. The most sophisticated microfluidic systems developed by now are Point-of-Care systems, that are based on Labon-Chip technologies. As these subfields are very extensive and go beyond the scope of this review, some carefully chosen additional review papers are provided.

An innovative rapid prototyping technique for embedding microcomponents in PDMS replicas was developed and applied on a thermal mass flowmeter for closed loop micropump flowrate control. Crucial flowmeter design and thermal parameters were investigated with a 3-D fully coupled electro-thermal-fluidic model which was built in Comsol Multiphysics 5.2. The flowmeter was characterized for three distinct measuring configurations. For precise low flowrate applications, a sensor-heater-sensor flowmeter configuration with a constant heater temperature was found to be the most appropriate yielding the measuring range of 0 to 90 µL·min−1 and the sensitivity of 1.3 °C·µL−1·min in the lower flowrate range of 0 to 40 µL·min−1.

Exosomes, a type of nanovesicle, are distinct cellular entities specifically capable of carrying various cargos between cells. It has been hypothesized that exosomes, as an enriched source of biomolecules, may serve as biomarkers for various diseases. This review introduces general aspects of exosomes, presents the challenges in exosome research, discusses the potential of exosomes as biomarkers, and describes the contribution of microfluidic technology to enable their isolation and analysis for diagnostic and disease monitoring. Additionally, clinical applications of exosomes for diagnostic purposes are also summarized.

The formation and analyses of thin film Ag/AgCl reference electrode by two different methods were studied with aim to extend the lifetime and to determine the potential stability over time. To convert part of thin Ag film into AgCl, chemical formation in FeCl3 of different molarities and electrochemical formation in solution of 3 M NaCl were employed. Optical and SEM analyses of formed Ag/AgCl microstructure revealed that both methods result in uniform distribution of polycrystalline grains with size between 1-3 micrometers. Potential stability measurements were performed by measuring the potential of thin film reference electrode against standard calomel liquid junction electrode. When measuring potential difference in high molarity electrolyte (3 M NaCl), lifetime of thin film electrodes was found to be limited to few hours, though in weak solutions it can be maintained up to several days. Preliminary results showed good potential stability (<;1% change per hour). It was shown that additional passivation of AgCl layer by a thin PDMS layer significantly increased the lifetime of the electrode.

Quality control of piezoelectric micropumps is presented through design, fabrication process, operation, and characterization. The presented study resulted in the extraction of a minimal set of monitored parameters, which is a prerequisite for reliable and stable micropump operation. Micropump fabrication process steps, especially bonding process quality, in correlation with quality control of micropump constituent components (housing, elastomer, and piezoelectric actuator) provided an explanation for deterioration of common micropump characteristics, such as flow vs. backpressure, suction pressure, and excitation signal. These characteristics also manifested in deterioration of other important micropump properties, such as self-priming ability, bubble tolerance, long-term stability, heat dissipation, and temperature operating range. Besides air and DI water pumping, chemical compatibility of constituent materials was confirmed during successful long-term testing of micropumps by pumping media with different viscosity and aggressive media with low pH value. The extracted set of parameters defines input control for micropump fabrication process while at the same time establishes safe operating area of fabricated micropumps. The presented set of parameters provides quality control guidelines and enables a direct comparison from pump-to-pump or run-to-run variations and extraction of influencing design or fabrication parameters.

Piezoelectric micropumps are often used in advanced microfluidic applications where an accurate pressure, flow control and monitoring are required. In applications where a small flow (nl/min range) is needed, they often represent the most appropriate solution due to their small size and low power consumption. In order to maximize the micropump flow-rate and backpressure performance, the piezoelectric actuator driving signal has to be adapted for a specific application, where appropriate signal amplitude and frequency have to be determined. To investigate the dependence of the flow-rate and backpressure on various driving signal parameters, a low-cost, miniature high-voltage piezoelectric micropump driving module is designed, fabricated and characterized. Implemented driver features low power consumption (max. 55 mA @ 12 V) and can achieve amplitudes of up to 250 V-PP in the 400 Hz frequency range.

High efficiency piezoelectric micropump driving module with programmable slew-rate and dead-time has been designed, implemented and characterized for driving custom made piezoelectric micropumps. Developed driver enables independent setting of several rectangular output signal parameters, such as frequency, positive and negative amplitudes, slew-rates, dead time, and modes of operation (pump/valve). Implemented driver can achieve amplitudes up to 250 VPP on a frequency range from DC to 1 kHz, slew-rate up to 18 V/mu s at maximum power consumption 1.6 W (180 mA @ 9 V). In comparison with our previous driver with RC charge/discharge signal shape, presented version increases air flow capability of micropumps from 1.6 sccm to 4.2 sccm. It enables driving of 200 mu m thick PZT actuators with 12 nF capacitance.

Cholinesterase inhibitors are widely used as pesticides, as chemical warfare agents and as drugs to treat symptoms of Alzheimer’s disease. Therefore, it is a high need to develop methods for their detection which are fast, sensitive, and reliable. This paper reports a preliminary work in the development of an electrochemical biosensor based on acetylcholinesterase (AChE) which is constructed by immobilization layers – cysteamine/glutaraldehyde/AChE on thin layer gold electrode for detection of cholinesterase inhibitors. Eserine (physostigmine) was used as a test inhibitor. The enzyme immobilization efficacy was evaluated by measuring activity of immobilized enzyme via Ellman’s method. The enzyme activity of the initial reduction of 33% in five days remained after that stable for at least one week. Chronoamperometric response to substrate acetylthiocholine chloride (ATCl) was assumed to follow Michaelis-Menten kinetics. After exposure biosensor to 25 mM eserine for 10 min, 70% inhibition of enzyme was detected. Reactivation factor of inhibited AChE was determined as 0.016 min-1.

For a cost-efficient micropump driving module, a topology with two mutually exclusive SMPS boost converters is proposed. Its disadvantage is a synthesis of the voltage-asymmetric excitation signal when the module is connected to a piezoelectric load. To investigate the cause of the asymmetry, the impedance of polarized and depolarized piezoelectric actuators from three different vendors is measured. It is shown that the voltage asymmetry of a synthesized signal is a result of the piezoelectric actuator polarization and that the degree of the signal asymmetry significantly affects the micropump flowrate and backpressure performance characteristics. Since the micropump performance is maximized when driven by a voltage-symmetric signal, a solution by fine-tuning of signal duty cycle for providing voltage symmetry is proposed.

An experimental study of in vivo insulin delivery through microinjection by using hollow silicon microneedle array is presented. A case study was carried out on a healthy human subject in vivo to determine the influence of delivery parameters on drug transfer efficiency. As a microinjection device, a hollow microneedle array (13 × 13 mm2) having 100 microneedles (220 µm high, 130 µm-outer diameter and 50 µm-inner diameter) was designed and fabricated using classical microfabrication techniques. The efficiency of the delivery process was first characterized using methylene blue and a saline solution. Based on these results, the transfer efficiency was found to be predominantly limited by the inability of viable epidermis to absorb and allow higher drug transport toward the capillary-rich region. Two types of fast-acting insulin were used to provide evidence of efficient delivery by hollow MNA to a human subject. By performing blood analyses, infusion of more-concentrated insulin (200 IU/mL, international units (IU)) exhibited similar blood glucose level drop (5–7%) compared to insulin of standard concentration (100 IU/mL), however, significant increase of serum insulin (40–50%) with respect to the preinfusion values was determined. This was additionally confirmed by a distinctive increase of insulin to C-peptide ratio as compared to preinfusion ratio. Moreover, we noticed that this route of administration mimics a multiple dose regimen, able to get a “steady state” for insulin plasma concentration.

Arterial oscillography (AO) is a non-invasive pneumatic technique for measurement of blood volume changes inside an organ or body part. In presented study, a peripheral arterial disease (PAD) of 19 individuals (35 legs) was measured using AO prototype instruments. The results of AO evaluation were compared to results of computed tomography angiography (CTA), which is the gold standard for diagnosis of PAD. The sensitivity and specificity of AO prototype instrument in amount of 79% and 81%, respectively was calculated.

Cell transplantation traditionally employs needles to inject donor cells into tissues to treat certain diseases. However, it is difficult for the current method to achieve multiple parallel equidistant injections, which are ideal for cell therapy. This paper presents a new cell transplantation method using an array of ultrathin microneedles. The main characteristic of the needles is their high aspect ratio: each needle is 500 μm long, and has a 50 μm diameter and a very thin wall (2 μm-thick SiO2 and 1.5 μm-thick Si3N4). An array of such microneedles was successfully used to inject fluorescently labeled Mardin–Darby canine kidney cells into rat liver tissue. Viability of the cells inserted using this method was verified after 5 days. Preliminary results show that this type of microneedle array can be used for cell therapy.

The present paper proposed a simple method using a double softlithography process for the fabrication of microneedles (MNs) arrays. A biocompatible UV curable polymer, Norland Optic Adhesive-NOA63 was selected to fabricate the solid hydrophilic microneedles. The geometry and the penetration capabilities of the newly fabricated microneedles were evaluated by optical imaging and microCT. The results evidenced that the length of the newly created MNs was acceptable for the intended purpose. The insertion tests evaluated the sharpness and robustness of the NOA63 MNs: the MNs were able to pierce the skin samples. These tests also highlighted the influence of the insertion force upon the penetration capability. The NOA63 MNs proved compliant with the general requirements. Moreover, they presented the advantage of a low-cost fabrication process. Therefore, the newly created MNs are promising alternative devices able to disrupt effectively the cutaneous barrier.

Study of DC sputtered Ti/Pt thin film layers on SiO2/n-Si substrate with the emphasis on post deposition heat treatment is presented. Microstructural and morphological properties of Ti/Pt thin films annealed in the range 300-700 degrees C in air are investigated and correlated with measured electrical properties. AES depth profile and composition of the sample annealed at 400 degrees C and 700 degrees C showed significant diffusion of Ti throughout the Pt layer toward surface, accompanied with enhanced oxygen incorporation, while keeping rather constant TiOx composition throughout the structure. AFM and SEM analyses of Ti/Pt film morphology showed that Pt grain size was almost temperature independent up to 400 degrees C, while above 500 degrees C, grain growth was enhanced. XPS analyses confirmed that most of Ti incorporated in the film was in oxide state (Ti4+) after annealing at 700 degrees C. EBSD analyses confirmed strong (111) texture of Pt polycrystalline grains annealed above 500 degrees C. Resistance of meandered Ti/Pt resistors was found to decrease significantly above 500 degrees C and complies well with the microstructural rearrangements determined by AFM and AES analyses. It was further determined that by increasing the annealing temperature from 300 degrees C to 700 degrees C, a monotonic increase of temperature coefficient of resistance from 1400 ppm/degrees C to 2400 ppm/degrees C, respectively, was obtained. This represents a considerable, improvement in sensitivity of Ti/Pt layers used as a temperature sensing devices. Resistance exhibited linear temperature dependency with nonlinearity better than 0.84%. (C) 2017 Elsevier B.V. All rights reserved.

Two room-temperature bonding processes for thermoplastic-PDMS polymer covalent bonding based on the organic substrate surface functionalization by means of organofunctional silanes APTES and amine-PDMS linker were developed and applied. The efficiency of covalent bonding was evaluated by measuring water contact angles on oxygen plasma pretreated surfaces and by measuring burst pressure on fabricated test devices. Developed amine-PDMS linker bonding process resulted in bond strength of 5 bar and 2 bar on continuous pressure of air and water respectively, while water initiated the hydrolysis of covalent bonds established via the modified APTES bonding process. Both bonding processes were applied on piezoelectric micropumps where glass substrate was replaced by thermoplastic substrate. Micropumps employing amine-PDMS linker exhibit no deterioration in their performance after eight weeks of continuous operation.