Advanced Microfabrication Research Articles

Playing with active matter

In the past 20 years, active matter has been a very successful research field, bridging the fundamental physics of nonequilibrium thermodynamics with applications in robotics, biology, and medicine. Active particles, contrary to Brownian particles, can harness energy to generate complex motions and emerging behaviors. Most active-matter experiments are performed with microscopic particles and require advanced microfabrication and microscopy techniques. Here, we propose some macroscopic experiments with active matter employing commercially available toy robots (the Hexbugs). We show how they can be easily modified to perform regular and chiral active Brownian motion and demonstrate through experiments fundamental signatures of active systems such as how energy and momentum are harvested from an active bath, how obstacles can sort active particles by chirality, and how active fluctuations induce attraction between planar objects (a Casimir-like effect). These demonstrations enable hands-on experimentation with active matter and showcase widely used analysis methods.

Self-Calibratable Absolute Modular Rotary Encoder: Development and Experimental Research.

Advanced microfabrication technologies have revolutionized the field of reflective encoders by integrating all necessary optical components and electronics into a miniature single-chip solution. Contemporary semiconductor sensors could operate at wide tolerance ranges that make them ideal for integration into compact and lightweight modular encoder kit systems. However, in order to achieve the high accuracy of the operating encoder, precise mechanical installation is still needed. To overcome this issue and exploit the full potential of modern sensors, the self-calibratable absolute modular rotary encoder is developed. The equal division average (EDA) method by combining the angular position readings from multiple optical sensors is used to simplify the installation process and ensure the high accuracy of the system. The produced prototype encoder is experimentally tested vs. the reference encoder and the measurement deviations of using different numbers and arrangements of optical sensors are determined. The obtained results show encoder ability to handle the mounting errors and minimize the initial system deviation by more than 90%.

Coupling Microdroplet-Based Sample Preparation, Multiplexed Isobaric Labeling, and Nanoflow Peptide Fractionation for Deep Proteome Profiling of the Tissue Microenvironment.

There is increasing interest in developing in-depth proteomic approaches for mapping tissue heterogeneity in a cell-type-specific manner to better understand and predict the function of complex biological systems such as human organs. Existing spatially resolved proteomics technologies cannot provide deep proteome coverage due to limited sensitivity and poor sample recovery. Herein, we seamlessly combined laser capture microdissection with a low-volume sample processing technology that includes a microfluidic device named microPOTS (microdroplet processing in one pot for trace samples), multiplexed isobaric labeling, and a nanoflow peptide fractionation approach. The integrated workflow allowed us to maximize proteome coverage of laser-isolated tissue samples containing nanogram levels of proteins. We demonstrated that the deep spatial proteomics platform can quantify more than 5000 unique proteins from a small-sized human pancreatic tissue pixel (∼60,000 μm2) and differentiate unique protein abundance patterns in pancreas. Furthermore, the use of the microPOTS chip eliminated the requirement for advanced microfabrication capabilities and specialized nanoliter liquid handling equipment, making it more accessible to proteomic laboratories.

A High-Aspect-Ratio Deterministic Lateral Displacement Array for High-Throughput Fractionation.

Future industrial applications of microparticle fractionation with deterministic lateral displacement (DLD) devices are hindered by exceedingly low throughput rates. To enable the necessary high-volume flows, high flow velocities as well as high aspect ratios in DLD devices have to be investigated. However, no experimental studies have yet been conducted on the fractionation of bi-disperse suspensions containing particles below 10 µm with DLD at a Reynolds number (Re) above 60. Furthermore, devices with an aspect ratio of more than 4:1, which require advanced microfabrication, are not known in the DLD literature. Therefore, we developed a suitable process with deep reactive ion etching of silicon and anodic bonding of a glass lid to create pressure-resistant arrays. With a depth of 120 µm and a gap of 23 µm between posts, a high aspect ratio of 6:1 was realized, and devices were investigated using simulations and fractionation experiments. With the two-segmented array of 3° and 7° row shifts, critical diameters of 8 µm and 12 µm were calculated for low Re conditions, but it was already known that vortices behind the posts can shift these values to lower critical diameters. Suspensions with polystyrene particles in different combinations were injected with an overall flow rate of up to 15 mL/min, corresponding to Re values of up to 90. Suspensions containing particle combinations of 2 µm with 10 µm as well as 5 µm with 10 µm were successfully fractionated, even at the highest flow rate. Under these conditions, a slight widening of the displacement position was observed, but there was no further reduction in the critical size as it was for Re = 60. With an unprecedented fractionation throughput of nearly 1 L per hour, entirely new applications are being developed for chemical, pharmaceutical, and recycling technologies.

Procedure in developing a longitudinal-torsional vibration-assisted micro-milling system

Micromachining is an advanced microfabrication technique for micro-sized or micro-accuracy products through subtractive manufacturing such as micro-milling. Vibration-assisted machining (VAM) is a method in which small amplitude vibrations are applied to the tool or workpiece to enhance the fabrication process. Milling results could be improved by adding longitudinal and torsional vibration to the tool using piezoelectric components vibrating at the ultrasonic frequency with an amplitude of less than 1 μm is used. A slip ring is required to transmit electric power from a static structure to a rotating frame. After the power has been transmitted to the system, an ultrasonic horn, called an acoustic horn or sonotrode, amplifies the vibrations at the tool’s tip. Since the excitation vibration is only longitudinal, the magnification of the vibration at the tooltip is also only longitudinal. Grooves are added to the side of the ultrasonic horn to produce torsional vibrations. This vibration is then simulated through finite element analysis software, explicitly using explicit dynamics. A 3D simulation is run for a quarter cycle of micro-milling through a Ti-6Al-4V material. It could be concluded that the LTVAM application may improve machining quality, such as temperature reduction of up to 9%, cutting force reduction of up to 35%, and surface roughness improvement of up to 27%.

Wearable ultrasound technology

The use of wearable electronic devices that can acquire vital signs from the human body noninvasively and continuously is a significant trend for healthcare. The combination of materials design and advanced microfabrication techniques enables the integration of various components and devices onto a wearable platform, resulting in functional systems with minimal limitations on the human body. Physiological signals from deep tissues are particularly valuable as they have a stronger and faster correlation with the internal events within the body compared to signals obtained from the surface of the skin. In this presentation, I will demonstrate a soft ultrasonic technology that can noninvasively and continuously acquire dynamic information about deep tissues and central organs. I will also showcase examples of this technology's use in recording blood pressure and flow waveforms in central vessels, monitoring cardiac chamber activities, and measuring core body temperatures. The soft ultrasonic technology presented represents a platform with vast potential for applications in consumer electronics, defense medicine, and clinical practices.

Building Biomaterials to Mimic 3D Cell-Cell Junctions.

Cell-cell interactions typically occur in a 3D context that is distinct from conventional 2D cell-substrate interactions in a Petri dish. Here, we describe a benchtop method to combine a 2D extracellular matrix surface with a 3D, vertical boundary functionalized with the extracellular domain of E-cadherin. The methodology is suitable for any biology laboratory without requiring advanced microfabrication equipment or training. Overall, this cell-mimetic interface uniquely recapitulates key aspects of cell-cell adhesion and can serve as a versatile, reductionist technique to study general cell-cell interactions in a 3D context.

Design and Analysis of a Rotational Mixer to produce 3D Bioprinting Gyroid-Helical-Patterned Scaffolds for Tissue Engineering Applications.

Tissue engineering scaffolds require complex networks for nutrient diffusion and cell attachment. They must have specific surface area and curvature, and often need a multimaterial composition, demanding advanced micro-fabrication methods. 3D extrusion bioprinting offers versatility to manufacture different scaffold, and strategies for multimaterial printing have been introduced. We propose a method to fabricate scaffolds based on gyroid-helical-patterned microfibers, providing a platform to study the effect of the gyroid minimum curvature on cellular processes, since the geometry wont be layer-by-layer approximated. The pattern is obtained by mixing inks using a gyroid-helix shaped rotational mixer, modifying the extruder of a conventional 3D printer. The mixer was simulated using computational fluid dynamics tools, varying the volumetric flow to obtain different gyroid-thickness. Due to its surface area minimization, it shows lower energy requirements than state-of-art fluid mixers, with a pressure drop of 1.7%, a power number of 39, and a rotation-induced shear stress of ∼400 Pa, enabling the use of cell-embedded bioinks.

Beginner's Guide to Micro- and Nanoscale Electrochemical Additive Manufacturing.

Electrochemical additive manufacturing is an advanced microfabrication technology capable of producing features of almost unlimited geometrical complexity. A unique combination of the capacity to process conductive materials, design freedom, and micro- to nanoscale resolution offered by these electrochemical techniques promises tremendous opportunities for a multitude of future applications spanning microelectronics, sensing, robotics, and energy storage. This review aims to equip readers with the basic principles of electrochemical 3D printing at the small length scale. By describing the basic principles of electrochemical additive manufacturing technology and using the recent advances in the field, this beginner's guide illustrates how controlling the fundamental phenomena that underpin the print process can be used to vary dimensions, morphology, and microstructure of printed structures.

Fabricating 1D stretchable fiber-shaped electronics based on inkjet printing technology for wearable applications

Advanced microfabrication on small and curved fiber surfaces remains a critical challenge and an urgent need to develop high-performance fiber-shaped electronics and advance the next generation of wearable electronics technology. In this study, we propose the preparation of 1D stretchable fiber-shaped electronics via inkjet printing technology for wearable applications. Utilizing self-built precision rotary inkjet printing equipment and a surface chemical modification process, we achieve high-precision and customizable microfabrication onto ultra-low diameter fiber surfaces (minimum printing line width of 133 µm and a printable fiber diameter as low as 500 µm with a large curvature of 4000 m−1). More importantly, this fabricating method is non-destructive and can prepare 1D stretchable conductors by printing conductive inks with stretchable structures and optimizing various synthetic fibers, which exhibit remarkable conductivity, mechanical stability, and strain-insensitive properties in practical applications. Furthermore, we demonstrate the performance of several 1D stretchable electronics applications, including a fiber-shaped electrothermal device, triboelectric strain sensor, and supercapacitor. Our work will greatly promote the development of 1D fiber-shaped electronics and smart textiles with wearability, high performance, functional diversification, and low cost.

A microfluidic chip for geoelectrical monitoring of critical zone processes.

We miniaturize geoelectrical acquisition using advanced microfabrication technologies to investigate coupled processes in the critical zone. We focus on the development of the complex electrical conductivity acquisition with the spectral induced polarization (SIP) method on a microfluidic chip equipped with electrodes. SIP is an innovative detection method that has the potential to monitor biogeochemical processes. However, due to the lack of microscale visualization of the processes, the interpretation of the SIP response remains under debate. This approach at the micrometer scale allows working in well-controlled conditions, with real-time monitoring by high-speed and high-resolution microscopy. It enables direct observation of microscopic reactive transport processes in the critical zone. We monitor the dissolution of pure calcite, a common geochemical reaction studied as an analog of the water-mineral interactions. We highlight the strong correlation between SIP response and dissolution through image processing. These results demonstrate that the proposed technological advancement will provide a further understanding of the critical zone processes through SIP observation.

Erratum to: Enabling electrically tunable radio frequency components with advanced microfabrication and thin film techniques

Erratum to: Enabling electrically tunable radio frequency components with advanced microfabrication and thin film techniques

Enabling electrically tunable radio frequency components with advanced microfabrication and thin film techniques

Enabling electrically tunable radio frequency components with advanced microfabrication and thin film techniques

Preparation Technology of Stretchable Electrode Based on Laser Cutting

Wearable electronics have showed their profound impact in military, sports, medical and other fields, but their large-scale applications are still limited due to high manufacturing costs. As an advanced micro-fabrication process, laser processing technology has the advantages of high speed, high flexibility, strong controllability, environmental protection and non-contact in preparing micro-nano structures of wearable electronics. In this paper, a 355 nm ultraviolet laser was used to pattern the copper foil pasted on the flexible substrate, and the interconnection electrodes and wires were constructed. A processing method of multi-parallel line laser cutting and high-speed laser scanning is proposed to separate and assist in peeling off excess copper foil. The process parameters are optimized. A stretchable 3 × 3 light-emitting diode (LED) array was prepared and its performance was tested. The results showed that the LED array can work normally under the conditions of folding, bending and stretching, and the stretch rate can reach more than 50%. A stretchable temperature measurement circuit that can be attached to a curved surface was further fabricated, which proves the feasibility of this process in the fabrication of small-scale flexible wearable electronic devices. Requiring no wet etching or masking process, the proposed process is an efficient, simple and low-cost method for the fabrication of stretchable circuits.

Construction of in vitro 3-D model for lung cancer-cell metastasis study

BackgroundCancer metastasis is the main cause of mortality in cancer patients. However, the drugs targeting metastasis processes are still lacking, which is partially due to the short of effective in vitro model for cell invasion studies. The traditional 2-D culture method cannot reveal the interaction between cells and the surrounding extracellular matrix during invasion process, while the animal models usually are too complex to explain mechanisms in detail. Therefore, a precise and efficient 3-D in vitro model is highly desirable for cell invasion studies and drug screening tests.MethodsPrecise micro-fabrication techniques are developed and integrated with soft hydrogels for constructing of 3-D lung-cancer micro-environment, mimicking the pulmonary gland or alveoli as in vivo.ResultsA 3-D in vitro model for cancer cell culture and metastasis studies is developed with advanced micro-fabrication technique, combining microfluidic system with soft hydrogel. The constructed microfluidic platform can provide nutrition and bio-chemical factors in a continuous transportation mode and has the potential to form stable chemical gradient for cancer invasion research. Hundreds of micro-chamber arrays are constructed within the collagen gel, ensuring that all surrounding substrates for tumor cells are composed of natural collagen hydrogel, like the in vivo micro-environment. The 3-D in vitro model can also provide a fully transparent platform for the visual observation of the cell morphology, proliferation, invasion, cell-assembly, and even the protein expression by immune-fluorescent tests if needed.The lung-cancer cells A549 and normal lung epithelial cells (HPAEpiCs) have been seeded into the 3-D system. It is found out that cells can normally proliferate in the microwells for a long period. Moreover, although the cancer cells A549 and alveolar epithelial cells HPAEpiCs have the similar morphology on 2-D solid substrate, in the 3-D system the cancer cells A549 distributed sparsely as single round cells on the extracellular matrix (ECM) when they attached to the substrate, while the normal lung epithelial cells can form cell aggregates, like the structure of normal tissue. Importantly, cancer cells cultured in the 3-D in vitro model can exhibit the interaction between cells and extracellular matrix. As shown in the confocal microscope images, the A549 cells present round and isolated morphology without much invasion into ECM, while starting from around Day 5, cells changed their shape to be spindle-like, as in mesenchymal morphology, and then started to destroy the surrounding ECM and invade out of the micro-chambers.ConclusionsA 3-D in vitro model is constructed for cancer cell invasion studies, combining the microfluidic system and micro-chamber structures within hydrogel. To show the invasion process of lung cancer cells, the cell morphology, proliferation, and invasion process are all analyzed. The results confirmed that the micro-environment in the 3-D model is vital for revealing the lung cancer cell invasion as in vivo.

Scalable Thousand Channel Penetrating Microneedle Arrays on Flex for Multimodal and Large Area Coverage BrainMachine Interfaces.

The Utah array powers cutting-edge projects for restoration of neurological function, such as BrainGate, but the underlying electrode technology has itself advanced little in the last three decades. Here, advanced dual-side lithographic microfabrication processes is exploited to demonstrate a 1024-channel penetrating silicon microneedle array (SiMNA) that is scalable in its recording capabilities and cortical coverage and is suitable for clinical translation. The SiMNA is the first penetrating microneedle array with a flexible backing that affords compliancy to brain movements. In addition, the SiMNA is optically transparent permitting simultaneous optical and electrophysiological interrogation of neuronal activity. The SiMNA is used to demonstrate reliable recordings of spontaneous and evoked field potentials and of single unit activity in chronically implanted mice for up to 196 days in response to optogenetic and to whisker air-puff stimuli. Significantly, the 1024-channel SiMNA establishes detailed spatiotemporal mapping of broadband brain activity in rats. This novel scalable and biocompatible SiMNA with its multimodal capability and sensitivity to broadband brain activity will accelerate the progress in fundamental neurophysiological investigations and establishes a new milestone for penetrating and large area coverage microelectrode arrays for brain-machine interfaces.

RF Performance Benchmarking of TSV Integrated Surface Electrode Ion Trap for Quantum Computing

Surface electrode ion trap is highly promising for practical quantum computing due to its superior controllability on the trapped ions. With advanced microfabrication techniques, silicon has been developed as an ion trap substrate for delicate surface electrodes design and monolithic electro-optical components integration. However, the high RF loss of silicon hinders the possible large-scale implementation. In this work, we demonstrate a through silicon via (TSV) integrated ion trap, which has low RF loss due to the elimination of wire bonding (WB) pads on the surface and the miniaturization of form factor. We also fabricate two types of conventional WB traps with or without a grounding screen layer. The RF performances of different ion traps are tested and compared, in terms of on-chip S-parameter, postpackaging resonance, and resulting power loss. The results show that the TSV trap has low S21 (~0.2 dB at 50 MHz), high <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$Q$ </tex-math></inline-formula> factor (~22), and low power loss (0.26 W) compared to WB traps. In addition, 3-D finite element modeling (FEM) is employed for electric field visualization and RF loss analysis of different traps. The extracted results from the modeling show a decent agreement with the measurements. In addition to various RF tests, the design, fabrication, and ion trapping operation of different ion traps are presented. This work provides insights into RF loss of ion trapping devices and offers a new solution for RF loss reduction.

Fast prototyping using 3D printed templates and flexible fluoropolymer microcapillary films offers enhanced micromixing in immobilised (bio)catalytic reactions

Microreactors offer large surface-area-to-volume (SAV) ratios and short diffusion distances, yet, even at sub-millimetre space, there remains a level of mass transfer control of reactions. This can be minimised using passive micromixers currently requiring access to advanced microfabrication techniques. We report the fast fabrication and in-depth micromixing characterisation of inexpensive non-linear microstructure prototypes using, for the first time, a flexible fluoropolymer microcapillary film (MCF) re-shaped, post-extrusion, with 3D printed templates offering in-flow enhancement of mass transfer in immobilised (bio)catalytic reactions not previously studied for this type of micro-engineered material. The versatile “push-and-click” 3D printed templates allow one-step production of multi-bored, non-invasive micromixers with simple architectures, namely ‘square’, ‘zigzag’ and ‘wavy’ geometries without the limitations of conventional microfluidic devices. The passive micromixers were numerically evaluated using Computational Fluid Dynamics (CFDs) and extensively validated experimentally using novel Residence time distribution (RTD) data which assessed the role of Reynold numbers (0.6 – 60) and molecular diffusion coefficients (10−6 –10−11 m2/s), providing significant in-depth understanding of fluid flow distribution. By evaluating the in-flow oxidative coupling reaction of o-phenylenediamine (OPD, a chromogenic substrate) to 2,3-diaminophenazine (DAP) with an immobilised enzyme, horseradish peroxidase (HRP), we demonstrated the reaction rates in the ‘square’ and ‘zigzag’ (sharp bends) were improved by ∼43 and ∼46% respectively, compared to straight microcapillaries. This is linked to enhanced radial fluid movement. The proposed prototypes can be readily tailored for facilitated fabrication of practical high-performance microreactors suited for heterogeneous assays or in-flow (bio)catalytic reactions in non-microdevice dedicated labs.

Whispering-gallery mode InGaN microdisks on GaN substrates.

Microdisks fabricated with III-nitride materials grown on GaN substrates are demonstrated, taking advantage of the high material quality of homoepitaxial films and advanced micro-fabrication processes. The epitaxial structure consists of InGaN/GaN multi-quantum wells (MQWs) sandwiched between AlGaN/GaN and InAlN/GaN superlattices as cladding layers for optical confinement. Due to lattice-matched growth with low dislocations, an internal quantum efficiency of ∼40% is attained, while the sidewalls of the etched 8 µm-diameter microdisks patterned by microsphere lithography are optically smooth to promote the formation of whispering-gallery modes (WGMs) within the circular optical cavities. Optically pumped lasing with low threshold of ∼5.2 mJ/cm2 and quality (Q) factor of ∼3000 at the dominant lasing wavelength of 436.8 nm has been observed. The microdisks also support electroluminescent operation, demonstrating WGMs consistent with the photoluminescence spectra and with finite-difference time-domain (FDTD) simulations.

(Invited) Adding a New Sensing Dimension to Soft Electronics: From the Skin to below the Skin

Soft electronic devices that can noninvasively and continuously acquire vital signs from the human body represent an important trend for healthcare. Combined strategies of materials design and advanced microfabrication allow the integration of a variety of components and devices on a soft platform, resulting in functional systems with minimal constraints on the human body. In this presentation, I will demonstrate a wearable multichannel patch that can sense a collection of signals from the human skin in a wireless mode. Additionally, integrating high-performance ultrasonic transducers on the stretchable substrate adds a new third dimension to the detection range of conventional soft electronics. Ultrasound waves can penetrate the skin and noninvasively capture dynamic events in deep tissues, such as blood pressure and blood flow waveforms in central arteries and veins. This soft platform holds profound implications for a wide range of applications in consumer electronics, sports medicine, defense, and clinical practices. Figure 1