High throughput clogging free microfluidic particle filter by femtosecond laser micromachining.

In recent decades, driven by the needs of industry and medicine, researchers have been investigating how to remove carefully from the main flow microscopic particles or clusters of them. Among all the approaches proposed, crossflow filtration is one of the most attractive as it provides a non-destructive, label-free and in-flow sorting method. In general, the separation performance shows capture and separation efficiencies ranging from 70% up to 100%. However, the maximum flow rate achievable (µL/min) is still orders of magnitude away from those suitable for clinical or industrial applications mainly due to the low stiffness of the materials typically used. In this work, we propose an innovative hydrodynamic-crossflow hybrid filter geometry, buried in a fused silica substrate by means of the femtosecond laser irradiation followed by chemical etching technique. The material high stiffness combined with the accuracy of our manufacturing technique allows the 3D fabrication of non-deformable channels with higher aspect ratio posts, while keeping the overall device dimensions compact. The filter performance has been validated through experiments with both Newtonian (water-based solution of microbeads) and non-Newtonian fluids (blood), achieving separation efficiencies of up to 94% and large particles recovery rates of 100%, even at very high flow rates (mL/h).

A Flexible Printed Circuit Board Based Microelectromechanical Field Mill with a Vertical Movement Shutter Driven by an Electrostatic Actuator.

Micromachined electric field mills have received much interest for the measurement of DC fields; however, conventional designs with lateral moving shutters could have shutter lifting in the presence of strong fields, which affects their performance. This paper presents a MEMS electric field mill utilizing a vertical movement shutter to address this issue. The sensor is designed and fabricated based on a flexible PCB substrate and is released using a laser-cutting process. The movement of the shutter is driven by an electrostatic actuator. When the driving signal is a sine wave, the shutter moves in the same direction during both the positive and negative half-periods. This facilitates the application of a lock-in amplifier to synchronize with the signal at twice the frequency of the driving signal. In experimental testing, when the vertical shutter is driven at a resonance of 840 Hz, the highest sensitivity of the sensor is achieved and is measured to be 5.1 V/kVm-1. The sensor also demonstrates a good linearity of 1.1% for measuring DC electric fields in the range of 1.25 kV/m to 25 kV/m.

A Method of Precise Auto-Calibration in a Micro-Electro-Mechanical System Accelerometer.

A novel design of a MEMS (Micro-Electromechanical System) capacitive accelerometer fabricated by surface micromachining, with a structure enabling precise auto-calibration during operation, is presented. Precise auto-calibration was introduced to ensure more accurate acceleration measurements compared to standard designs. The standard mechanical structure of the accelerometer (seismic mass integrated with elastic suspension and movable plates coupled with fixed plates forming a system of differential sensing capacitors) was equipped with three movable detection electrodes coupled with three fixed electrodes, thus creating three atypical tunneling displacement transducers detecting three specific positions of seismic mass with high precision, enabling the auto-calibration of the accelerometer while it was being operated. Auto-calibration is carried out by recording the accelerometer indication while the seismic mass occupies a specific position, which corresponds to a known value of acting acceleration determined in a pre-calibration process. The diagram and the design of the mechanical structure of the accelerometer, the block diagram of the electronic circuits, and the mathematical relationships used for auto-calibration are presented. The results of the simulation studies related to mechanical and electric phenomena are discussed.

Laser-based sample preparation for high-resolution X-ray-computed tomography of glasses and glass ceramics.

X-ray-computed tomography with sub-micron resolution (nano-CT) is one of the most useful techniques to examine the 3D microstructure of materials down to voxel sizes 10 nm. However, since size and shape of samples have considerable influence on acquisition time and data quality, adapted and universally applicable workflows are needed. Three novel workflows for sample preparation using ultra-short pulsed lasers are presented which allow for reproducible fabrication, safe extraction and mounting of samples. Their application potential is illustrated via nano-CT measurements of glass ceramics as well as a laser-modified glass. Since the according sample geometries take also the requirements of other analytical techniques such as transmission electron microscopy into account, samples prepared according to the new workflows can be furthermore seen as a starting point for correlative microstructural analyses involving multiple techniques.

A PVDF Receiver for Acoustic Monitoring of Microbubble-Mediated Ultrasound Brain Therapy.

The real-time monitoring of spectral characteristics of microbubble (MB) acoustic emissions permits the prediction of increases in blood-brain barrier (BBB) permeability and of tissue damage in MB-mediated focused ultrasound (FUS) brain therapy. Single-element passive cavitation detectors provide limited spatial information regarding MB activity, greatly affecting the performance of acoustic control. However, an array of receivers can be used to spatially map cavitation events and thus improve treatment control. The spectral content of the acoustic emissions provides additional information that can be correlated with the bio-effects, and wideband receivers can thus provide the most complete spectral information. Here, we develop a miniature polyvinylidene fluoride (PVDF thickness = 110 µm, active area = 1.2 mm2) broadband receiver for the acoustic monitoring of MBs. The receiver has superior sensitivity (2.36-3.87 V/MPa) to those of a commercial fibre-optic hydrophone in the low megahertz frequency range (0.51-5.4 MHz). The receiver also has a wide -6 dB acceptance angle (54 degrees at 1.1 MHz and 13 degrees at 5.4 MHz) and the ability to detect subharmonic and higher harmonic MB emissions in phantoms. The overall acoustic performance of this low-cost receiver indicates its suitability for the eventual use within an array for MB monitoring and mapping in preclinical studies.

Reciprocating Arc Silicon Strain Gauges.

Currently, silicon-strain-gauge-based diaphragm pressure sensors use four single-gauge chips for high-output sensitivity. However, the four-single-gauge configuration increases the number of glass frit bonds and the number of aluminum wire bonds, reducing the long-term stability, reliability, and yield of the diaphragm pressure sensor. In this study, a new design of general-purpose silicon strain gauges was developed to improve the sensor output voltage while reducing the number of bonds. The new gauges consist grid patterns with a reciprocating arc of silicon piezoresistors on a thin glass backing. The gauges make handling easier in the bonding process due to the use of thin glass for the gauge backing. The pressure sensors were tested under pressure ranging from 0 to 50 bar at five different temperatures, with a linear output with a typical sensitivity of approximately 16 mV/V/bar and an offset shift of -6 mV to 2 mV. The new approach also opens the possibility to extend arc strain gauges to half-bridge and full-bridge configurations to further reduce the number of glass frit and Al wire bonds in the diaphragm pressure sensor.

Half-Bridge Silicon Strain Gauges with Arc-Shaped Piezoresistors.

Half-bridge silicon strain gauges are widely used in the fabrication of diaphragm-type high-pressure sensors, but in some applications, they suffer from low output sensitivity because of mounting position constraints. Through a special design and fabrication approach, a new half-bridge silicon strain gauge comprising one arc gauge responding to tangential strain and another linear gauge measuring radial strain was developed using Silicon-on-Glass (SiOG) substrate technology. The tangential gauge consists of grid patterns, such as the reciprocating arc of silicon piezoresistors on a thin glass substrate. When two half-bridges are connected to form a full bridge with arc-shaped gauges that respond to tangential strain, they have the advantage of providing much higher output sensitivity than a conventional half-bridge. Pressure sensors tested under pressure ranging from 0 to 50 bar at five different temperatures indicate a linear output with a typical sensitivity of approximately 16 mV/V/bar, a maximum zero shift of 0.05% FS, and a span shift of 0.03% FS. The higher output level of pressure sensing gauges will provide greater signal strength, thus maintaining a better signal-to-noise ratio than conventional pressure sensors. The offset and span shift curves are quite linear across the operating temperature range, giving the end user the advantage of using very simple algorithms for temperature compensation of offset and span shift.

Resonant-Opto-Thermomechanical Oscillator (ROTMO): A Low-Power, Large Displacement, High-Frequency Optically Driven Microactuator.

A light-driven micromechanical oscillator is presented, which can be operated by a low optical power (in the mW, or even the µW range), can produce large mechanical displacements (>5-100 µm), and can be designed to operate at frequencies from sub-kHz up to more than 200 kHz. The actuation of the oscillator is achieved by an asymmetrically metal-coated optical microwire configured into a silica micromechanical oscillator. The metalized optical microwire confines and absorbs the light strongly over a short distance, which results in a controlled optical power conversion into heat, and, consequently, into mechanical actuation through the temperature rise and the difference in thermal expansions of the silica microwire and the asymmetrically applied metal layer. Mechanical displacements are amplified further by the resonance operation of the oscillator, which is driven by a low-power, harmonic optical excitation signal generated by a current-modulated laser diode. Proper selection of the micromechanical oscillator's geometrical configuration and materials allows for a high-frequency operation at large mechanical displacements of the oscillator, while relying on low excitation optical power. The presented concept of a fully optically driven micromechanical oscillator may, thus, present a basis for realization of new classes of actuated micro-opto-mechanical Systems and similar photonics microdevices.

Electrochemical nanoimprinting of silicon.

Scalable nanomanufacturing enables the commercialization of nanotechnology, particularly in applications such as nanophotonics, silicon photonics, photovoltaics, and biosensing. Nanoimprinting lithography (NIL) was the first scalable process to introduce 3D nanopatterning of polymeric films. Despite efforts to extend NIL's library of patternable media, imprinting of inorganic semiconductors has been plagued by concomitant generation of crystallography defects during imprinting. Here, we use an electrochemical nanoimprinting process-called Mac-Imprint-for directly patterning electronic-grade silicon with 3D microscale features. It is shown that stamps made of mesoporous metal catalysts allow for imprinting electronic-grade silicon without the concomitant generation of porous silicon damage while introducing mesoscale roughness. Unlike most NIL processes, Mac-Imprint does not rely on plastic deformation, and thus, it allows for replicating hard and brittle materials, such as silicon, from a reusable polymeric mold, which can be manufactured by almost any existing microfabrication technique.

Optical Fiber Probe Microcantilever Sensor Based on Fabry-Perot Interferometer.

Optical fiber Fabry-Perot sensors have long been the focus of researchers in sensing applications because of their unique advantages, including highly effective, simple light path, low cost, compact size, and easy fabrication. Microcantilever-based devices have been extensively explored in chemical and biological fields while the interrogation methods are still a challenge. The optical fiber probe microcantilever sensor is constructed with a microcantilever beam on an optical fiber, which opens the door for highly sensitive, as well as convenient readout. In this review, we summarize a wide variety of optical fiber probe microcantilever sensors based on Fabry-Perot interferometer. The operation principle of the optical fiber probe microcantilever sensor is introduced. The fabrication methods, materials, and sensing applications of an optical fiber probe microcantilever sensor with different structures are discussed in detail. The performances of different kinds of fiber probe microcantilever sensors are compared. We also prospect the possible development direction of optical fiber microcantilever sensors.

Microfluidic-Assisted Human Cancer Cells Culturing Platform for Space Biology Applications.

In the paper, the lab-on-chip platform applicable for the long-term cultivation of human cancer cells, as a solution meeting the demands of the CubeSat biological missions, is presented. For the first time, the selected cancer cell lines-UM-UC-3 and RT 112 were cultured on-chip for up to 50 days. The investigation was carried out in stationary conditions (without medium microflow) in ambient temperature and utilizing the microflow perfusion system in the incubation chamber assuring typical cultivation atmosphere (37 °C). All the experiments were performed to imitate the conditions that are provided before the biological mission starts (waiting for the rocket launch) and when the actual experiment is initialized on a CubeSat board in space microgravity. The results of the tests showed appropriate performance of the lab-on-chip platform, especially in the context of material and technological biocompatibility. Cultured cells were characterized by adequate morphology-high attachment rate and visible signs of proliferation in each of the experimental stage. These results are a good basis for further tests of the lab-on-chip platform in both terrestrial and space conditions. At the end of the manuscript, the authors provide some considerations regarding a potential 3-Unit CubeSat biological mission launched with Virgin Orbit company. The lab-on-chip platform was modelled to fit a 2-Unit autonomous laboratory payload.

Inkjet-Printed Functionalization of CMUT-Based CO2 Sensors.

The trade-off between the functionalization shift of the informative parameters and sensitivity of capacitive micromachined ultrasound transducers (CMUT)-based CO2 sensors is addressed, and the CMUT surface modification process by thin inkjet-printed polyethyleneimine (PEI) films is optimized. It was shown that by the proper preparation of the active CMUT surface and properly diluted PEI solution, it is possible to minimize the functionalization shift of the resonance frequency and the quality of the resonance and preserve the sensitivity potential. So, after optimization, we demonstrated 23.2 kHz frequency shift readings of the sensor with 16 MHz nominal frequency while in the gas chamber and switching between pure N2 and CO2. After testing the sensors with different PEI film thickness, it was confirmed that a 200 nm average thickness of a PEI film is an optimum, because this is the practical limit of CO2 absorption depth at given conditions. Additionally, we note that modification of the hydrophilic/hydrophobic properties of the CMUT surface allows changing the nanoscale surface roughness of the printed PEI film and controlling the area resolution of the inkjet functionalization by reducing the diameter of a single dot down to 150 µm by a commercially available printer cartridge.

Simple and Robust Microfabrication of Polymeric Piezoelectric Resonating MEMS Mass Sensors.

Resonating MEMS mass sensors are microdevices with broad applications in fields such as bioscience and biochemistry. Their advantageous surface-to-volume ratio makes their resonant frequency highly sensitive to variations in their mass induced by surface depositions. Recent global challenges, such as water quality monitoring or pandemic containment, have increased the need for low-cost (even disposable), rapidly fabricated microdevices as suitable detectors. Resonant MEMS mass sensors are among the best candidates. This paper introduces a simple and robust fabrication of polymeric piezoelectric resonating MEMS mass sensors. The microfabrication technology replaces the traditional layer-by-layer micromachining techniques with laser micromachining to gain extra simplicity. Membrane-based resonant sensors have been fabricated to test the technology. Their characterization results have proven that the technology is robust with good reproducibility (around 2% batch level variations in the resonant frequency). Initial tests for the MEMS mass sensors' sensitivity have indicated a sensitivity of 340 Hz/ng. The concept could be a starting point for developing low-cost MEMS sensing solutions for pandemic control, health examination, and pollution monitoring.

Rapid fabrication of teflon apertures by controlled high voltage pulses for formation of free standing planar lipid bilayer membrane.

Free standing artificial lipid bilayers are widely used in the study of biological pores. In these types of studies, the free standing planar lipid bilayer is formed over a micron-sized aperture consisting of either polymer such as Polytetrafluoroethylene (PTFE, Teflon) or glass. Teflon is chemically inert, has a low dielectric constant, and has a high electrical resistance which combined allow for obtaining low noise recordings. This study investigates the reproducible generation of micropores in the range of 50-100 microns in diameter in a Teflon film using a high energy discharge set-up. The discharger set-up consists of a microprocessor, a transformer, a voltage regulator, and is controlled by a computer. We compared two approaches for pore creation: single and multi-pulse methods. The results showed that the multi-pulse method produced narrower aperture size distributions and is more convenient for lipid bilayer formation, and thus would have a higher success rate than the single-pulse method. The bilayer stability experiments showed that the lipid bilayer lasts for more than 33 h. Finally, as a proof-of-concept, we show that the single and multi-channel electrophysiology experiments were successfully performed with the apertures created by using the mentioned discharger. In conclusion, the described discharger provides reproducible Teflon-pores in a cheap and easy-to-operate manner.

Rapid Makerspace Microfabrication and Characterization of 3D Microelectrode Arrays (3D MEAs) for Organ-on-a-Chip Models.

Integrated sensors in "on-a-chip" in vitro cellular models are a necessity for granularity in data collection required for advanced biosensors. As these models become more complex, the requirement for the integration of electrogenic cells is apparent. Interrogation of such cells, whether alone or within a connected cellular framework, are best achieved with microelectrodes, in the form of a microelectrode array (MEA). Makerspace microfabrication has thus far enabled novel and accessible approaches to meet these demands. Here, resin-based 3D printing, selective multimodal laser micromachining, and simple insulation strategies, define an approach to highly customizable and "on-demand" in vitro 3D MEA-based biosensor platforms. The scalability of this approach is aided by a novel makerspace microfabrication assisted technique denoted using the term Hypo-Rig. The MEA utilizes custom-defined metal microfabricated microelectrodes transitioned from planar (2D) to 3D using the Hypo-Rig. To simulate this transition process, COMSOL modeling is utilized to estimate transitionary forces and angles (with respect to normal). Practically, the Hypo-Rig demonstrated a force of ~40N, as well as a consistent 70° average angular transitionary performance which matched well with the COMSOL model. To illustrate the scalability potential, 3 × 3, 6 × 6, and 8 × 8 versions of the device were fabricated and characterized. The 3D MEAs, demonstrated impedance and phase measurements in the biologically relevant 1 kHz range of 45.4 kΩ, and -34.6° respectively, for polystyrene insulated, ~70µm sized microelectrodes.

Rapid and simple pressure-sensitive adhesive microdevice fabrication for sequence-specific capture and fluorescence detection of sepsis-related bacterial plasmid gene sequences.

Microbial resistance to currently available antibiotics poses a great threat in the global fight against infections. An important step in determining bacterial antibiotic resistance can be selective DNA sequence capture and fluorescence labeling. In this paper, we demonstrate the fabrication of simple, robust, inexpensive microfluidic devices for DNA capture and fluorescence detection of a model antibiotic resistance gene sequence. We laser micromachined polymethyl methacrylate microchannels and enclosed them using pressure-sensitive adhesive tapes. We then formed porous polymer monoliths with DNA capture probes in these microchannels and used them for sequence-specific capture, fluorescent labeling, and laser-induced fluorescence detection of picomolar (pM) concentrations of synthetic and plasmid antibiotic resistance gene targets. The relative fluorescence for the elution peaks increased with loaded target DNA concentration. We observed higher fluorescence signal and percent recovery for synthetic target DNA compared to plasmid DNA at the same loaded target concentration. A non-target gene was used for control experiments and produced < 3% capture relative to the same concentration of target. The full analysis process including device fabrication was completed in less than 90 min with a limit of detection of 30 pM. The simplicity of device fabrication and good DNA capture selectivity demonstrated herein have potential for application with processes for bacterial plasmid DNA extraction and single-particle counting to facilitate determination of antibiotic susceptibility. Graphical abstract.

Measurement of Micro Burr and Slot Widths through Image Processing: Comparison of Manual and Automated Measurements in Micro-Milling.

In this study, the burr and slot widths formed after the micro-milling process of Inconel 718 alloy were investigated using a rapid and accurate image processing method. The measurements were obtained using a user-defined subroutine for image processing. To determine the accuracy of the developed imaging process technique, the automated measurement results were compared against results measured using a manual measurement method. For the cutting experiments, Inconel 718 alloy was machined using several cutting tools with different geometry, such as the helix angle, axial rake angle, and number of cutting edges. The images of the burr and slots were captured using a scanning electron microscope (SEM). The captured images were processed with computer vision software, which was written in C++ programming language and open-sourced computer library (Open CV). According to the results, it was determined that there is a good correlation between automated and manual measurements of slot and burr widths. The accuracy of the proposed method is above 91%, 98%, and 99% for up milling, down milling, and slot measurements, respectively. The conducted study offers a user-friendly, fast, and accurate solution using computer vision (CV) technology by requiring only one SEM image as input to characterize slot and burr formation.

Fabrication of Microchannels in a Nodeless Antiresonant Hollow-Core Fiber Using Femtosecond Laser Pulses.

In this work, we present femtosecond laser cutting of microchannels in a nodeless antiresonant hollow-core fiber (ARHCF). Due to its ability to guide light in an air core combined with exceptional light-guiding properties, an ARHCF with a relatively non-complex structure has a high application potential for laser-based gas detection. To improve the gas flow into the fiber core, a series of 250 × 30 µm microchannels were reproducibly fabricated in the outer cladding of the ARHCF directly above the gap between the cladding capillaries using a femtosecond laser. The execution time of a single lateral cut for optimal process parameters was 7 min. It has been experimentally shown that the implementation of 25 microchannels introduces low transmission losses of 0.17 dB (<0.01 dB per single microchannel). The flexibility of the process in terms of the length of the performed microchannel was experimentally demonstrated, which confirms the usefulness of the proposed method. Furthermore, the performed experiments have indicated that the maximum bending radius for the ARHCF, with the processed 100 µm long microchannel that did not introduce its breaking, is 15 cm.

Development of Broadband High-Frequency Piezoelectric Micromachined Ultrasonic Transducer Array.

Piezoelectric micromachined ultrasonic transducers (PMUT) are promising elements to fabricate a two-dimensional (2D) array with a pitch small enough (approximately half wavelength) to form and receive arbitrary acoustic beams for medical imaging. However, PMUT arrays have so far failed to combine the wide, high-frequency bandwidth needed to achieve a high axial resolution. In this paper, a polydimethylsiloxane (PDMS) backing structure is introduced into the PMUTs to improve the device bandwidth while keeping a sub-wavelength (λ) pitch. We implement this backing on a 16 × 8 array with 75 µm pitch (3λ/4) with a 15 MHz working frequency. Adding the backing nearly doubles the bandwidth to 92% (-6 dB) and has little influence on the impulse response sensitivity. By widening the transducer bandwidth, this backing may enable using PMUT ultrasonic arrays for high-resolution 3D imaging.

Fabrication and characterization of femtosecond laser induced microwave frequency photonic fiber grating.

We proposed and fabricated a microwave-frequency photonic fiber grating (MPFG) by femtosecond laser micromachining on optical fibers. Illuminated by low coherent light source, the MPFG can be interrogated using proposed microwave photonic system to show the resonant peaks in microwave frequency domain. We studied the working principle and characteristics of this device. After that, we discussed the influence of fiber type, apodization and light source coherence lengths on this device. The device can also respond to ambient temperature change like fiber optic sensors.