Three-dimensional microfabrication is essential for microfluidics, micromechanical devices, optical components and architected materials, but current methods often trade resolution for speed: layer-by-layer and point-scanning approaches are slow, whereas fast volumetric printing lacks fine features. Here we show a single-exposure holographic lithography method that prints tall, high-resolution polymer microstructures in about 20 s. An inverse-designed phase mask-an optical element computed to shape light in three dimensions-projects a stable intensity pattern through thick photoresist, overcoming the blurring that normally limits deep photolithography. The method produces lattices, Penrose patterns and micromechanical structures with features as small as 6 µm across volumes up to 800 × 800 × 720 µm3 (corresponding to a print rate of 0.36 × 106 voxels/s), achieving aspect ratios above 120:1. The resulting structures guide liquid by capillary action and predictable mechanical behavior under compression. This approach offers a scalable route to complex 3D microstructures for microfluidics, MEMS, optics and architected materials.

Volumetric lithography offers a path to scalable fabrication of complex three-dimensional (3D) micro- and nanoscale architectures, yet existing approaches are limited by quasi-two-dimensional exposure physics or slow serial writing. We present a single-exposure volumetric fabrication strategy that enables creation of ultrahigh-aspect-ratio 3D structures with 6 um minimum features. An inverse-designed volumetric (holographic) phase mask generates an extended-depth-of-field intensity distribution inside a photoresist volume while preserving high transverse resolution, enabling uniform polymerization of the full volume in a single exposure. With exposure times of approximately 20 s, we fabricate lattices, Penrose tilings, and micromechanical elements with feature sizes down to 6 um over volumes up to 800 x 800 x 720 um^3, achieving aspect ratios exceeding 120:1. Quantitative analysis of capillary flow in hollow lattices demonstrates controlled fluid transport with an effective capillary transport coefficient of 176.3 um/(ms)^(1/2). In situ nanoindentation-based micro-compression reveals that the printed 3D hexagonal close-packed lattices exhibit a well-defined linear elastic regime with an effective Young's modulus of 5.7 GPa, followed by progressive buckling and densification characteristic of mechanically robust cellular architectures. Overlapping, tilted and multi-mask exposures further enable quasi-3D complex geometries with potential for reconfigurability. This approach establishes a new regime of high-throughput volumetric fabrication.

The clinical success of brain computer interfaces (BCI) depends on overcoming both biological and material challenges to ensure a long-term stable connection for neural recording and stimulation. This study systematically quantified damage that microelectrodes sustained during chronical implantation in three people with tetraplegia for 956–2130 days. Using scanning electron microscopy (SEM), we imaged 980 microelectrodes from eleven Neuroport arrays tipped with platinum (Pt, n = 8) and sputtered iridium oxide film (SIROF, n = 3). Arrays were implanted/explanted from posterior parietal, motor and somatosensory cortices across three clinical sites (Caltech/UCLA, Caltech/USC, APL/Johns Hopkins). From the electron micrographs, we quantified and correlated physical damage with functional outcomes measured in vivo, prior to explant (recording quality, noise, impedance and stimulation ability).Despite greater physical degradation, SIROF electrodes were twice as likely to record neural activity than Pt (measured by SNR). For SIROF, 1 kHz impedance significantly correlated with all physical damage metrics, recording metrics, and stimulation performance, suggesting a reliable measurement of in vivo degradation. We observed a new degradation type, primarily on stimulated electrodes (“pockmarked” vs “cracked”) electrodes; however, no significant degradation due to stimulation or amount of charge delivered. We hypothesize erosion of the silicon shank accelerates damage to the electrode / tissue interface, following damage to the tip metal.These findings link quantitative measurements to the microelectrodes’ physical condition and their capacity to record/stimulate. These data could lead to improved manufacturing processes or novel electrode designs to improve long-term performance of BCIs, making them vitally important as multi-year clinical trials of BCIs are becoming more common. Statement of significance Long-term performance stability of the electrode-tissue interface is essential for clinical viability of brain computer interface (BCI) devices; currently, materials degradation is a critical component for performance loss. Across three human participants, ten micro-electrode arrays (plus one control) were implanted for 956–2130 days. Using scanning electron microscopy (SEM), we analyzed degradation of 980 electrodes, comparing two types of commonly implanted electrode tip metals: Platinum (Pt) and Sputtered Iridium Oxide Film (SIROF). We correlated observed degradation with in vivo electrode performance: recording (signal-to-noise ratio, noise, impedance) and stimulation (evoked somatosensory percepts). We hypothesize penetration of the electrode tip by biotic processes leads to erosion of the supporting silicon core, which then accelerates further tip metal damage. These data could lead to improved manufacturing processes or novel electrode designs towards the goal of a stable BCI electrical interface, spanning a multi-decade participant lifetime.

The Utah electrode array (UEA) is a promising microelectrode technology with potential applications to assist patients with sensory loss, spinal cord injuries, and limb loss serving as neural prosthetics and brain-computer interfaces. Performance lifetime of microelectrodes, particularly when used for stimulation, remains one of the challenges for their clinical translation. This study characterizes the stimulation stability of an optimized iridium oxide (IrOx) research metallization for the UEA in comparison to the Blackrock standard practice metallization. The stimulation stability (Stim-Stab) protocol used electrochemical characterization and either 106 or 4 × 106 pulses at 2,100 µA (420 nC/ph) with longitudinal voltage transient measurements and physical characterization to quantify electrode lifetime. Approximately 50

The clinical success of brain computer interfaces (BCI) depends on overcoming both biological and material challenges to ensure a long-term stable connection for neural recording and stimulation. This study systematically quantified damage that microelectrodes sustained during chronical implantation in three people with tetraplegia for 956-2130 days. Using scanning electron microscopy (SEM), we imaged 980 microelectrodes from eleven Neuroport arrays tipped with platinum (Pt, n = 8) and sputtered iridium oxide film (SIROF, n = 3). Arrays were implanted/explanted from posterior parietal, motor and somatosensory cortices across three clinical sites (Caltech/UCLA, Caltech/USC, APL/Johns Hopkins). From the electron micrographs, we quantified and correlated physical damage with functional outcomes measured in vivo, prior to explant (recording quality, noise, impedance and stimulation ability). Despite greater physical degradation, SIROF electrodes were twice as likely to record neural activity than Pt (measured by SNR). For SIROF, 1 kHz impedance significantly correlated with all physical damage metrics, recording metrics, and stimulation performance, suggesting a reliable measurement of in vivo degradation. We observed a new degradation type, primarily on stimulated electrodes ("pockmarked" vs "cracked") electrodes; however, no significant degradation due to stimulation or amount of charge delivered. We hypothesize erosion of the silicon shank accelerates damage to the electrode / tissue interface, following damage to the tip metal. These findings link quantitative measurements to the microelectrodes' physical condition and their capacity to record/stimulate. These data could lead to improved manufacturing processes or novel electrode designs to improve long-term performance of BCIs, making them vitally important as multi-year clinical trials of BCIs are becoming more common. Statement of significance: Long-term performance stability of the electrode-tissue interface is essential for clinical viability of brain computer interface (BCI) devices; currently, materials degradation is a critical component for performance loss. Across three human participants, ten micro-electrode arrays (plus one control) were implanted for 956-2130 days. Using scanning electron microscopy (SEM), we analyzed degradation of 980 electrodes, comparing two types of commonly implanted electrode tip metals: Platinum (Pt) and Sputtered Iridium Oxide Film (SIROF). We correlated observed degradation with in vivo electrode performance: recording (signal-to-noise ratio, noise, impedance) and stimulation (evoked somatosensory percepts). We hypothesize penetration of the electrode tip by biotic processes leads to erosion of the supporting silicon core, which then accelerates further tip metal damage. These data could lead to improved manufacturing processes or novel electrode designs towards the goal of a stable BCI electrical interface, spanning a multi-decade participant lifetime.

This paper reports on a low power 1H-NMR sensor capable of detecting biomarkers and chemicals in the blood flowing through fingers. It uses a trampoline magnetometer, and coils to non-intrusively detect chemicals with unpaired nuclei such as 1H. Molecular electrons shield the external fields by different amounts in different chemicals enabling their unique identification by the Larmor precession frequencies (omega Larmour) of their 1H nuclei. The NMR described here uses high sensitivity, high-Q, 100 kHz - 400 kHz resonant trampoline magnetometers with relative immunity to acoustic noise.

The main objective of this work is to study the coupling between spin transitions or excitations and mechanical excitations in micro-opto-electro-mechanical devices to design efficient spin sensors for quantum computers. We report the effect of spin polarization in negatively charged nitrogen-vacancy (NV-) color centers in diamond and in yttrium-iron-garnets integrated with mechanical resonators. Two mechanical resonators consisting of a stoichiometric silicon nitride trampoline and a piezoelectric disk were used. The results clearly show spin transitions and mechanical vibrations of the resonators are coupled through magneto-elastic and magneto-striction effects.

By engineering the point-spread function (PSF) of single molecules, different fluorophore species can be imaged simultaneously and distinguished by their unique PSF patterns. Here, we insert a silicon-dioxide phase plate at the Fourier plane of the detection path of a wide-field fluorescence microscope to produce distinguishable PSFs (X-PSFs) at different wavelengths. We demonstrate that the resulting PSFs can be localized spatially and spectrally using a maximum-likelihood estimation algorithm and can be utilized for hyper-spectral super-resolution microscopy of biological samples. We produced superresolution images of fixed U2OS cells using X-PSFs for dSTORM imaging with simultaneous illumination of up to three fluorophore species. The species were distinguished only by the PSF pattern. We achieved ∼21-nm lateral localization precision (FWHM) and ∼17-nm axial precision (FWHM) with an average of 1,800 - 3,500 photons per PSF and a background as high as 130 - 400 photons per pixel. The modified PSF distinguished fluorescent probes with ∼80 nm separation between spectral peaks.

We experimentally demonstrate an inverse-designed monochromatic compact dual-layer multi-level diffractive lens integration with wide field-of-view over 100°, ultra-thin (70um total thickness), super-light (< 1 gram) and high resolution, providing new applications for lightweight camera designs.

Objective We developed robust and cost-effective cuff Flex electrodes to facilitate bioelectronic medicine research in mouse models. They utilize polyimide (PI) as a dielectric insulation and iridium oxide (IrO x ) for the electrodes, and are designed to interface small autonomic and somatic nerves (e.g. mouse vagus nerve). Approach Flex electrodes were made using micro-fabrication technology, and innovative integration processes were developed to enable reliable acute and chronic vagus nerve interfaces. The electrochemical properties of Flex electrodes were characterized. Moreover, accelerated aging at 57 °C and stimulation-stability (Stim-Stab) testing (10 9 pulses at ∼ 1.59 mC/cm 2 /phase) were performed to evaluate the lifetime of the PI encapsulation and IrO x electrodes, respectively. Flex electrodes efficacy was demonstrated by stimulating the mouse vagus nerve (∼100 µm) and measuring heart and respiratory rate changes as biomarkers. Results Cost effective and robust lead and connector integration strategies were demonstrated, including small helical leads that improved the lead elongation by > 7x. PI encapsulation had stable impedance spectra for at least 336 days for interdigitated electrodes. Stim-Stab testing using an aggressive paradigm and rigorous optical and electrical characterization, revealed that half of electrodes showed less than minor damage at the endpoints. A trend of decreasing respiratory rate with stimulation current reached statistical significance at 500 µA, demonstrating efficacy for Flex electrodes. Significance Flex electrodes offer demonstrated efficacy, low impedance (443 ± 32 Ω at 10 3 Hz), excellent bench test stability, and cost-effective fabrication. Acute devices are easy to integrate, and mechanically robust chronic devices will be investigated in vivo in future studies. These characteristics make the electrodes well-positioned to advance bioelectronics medicine research by 1) enabling reliable studies with statistically relevant populations of acute mouse models, and 2) offering the potential for a technology that can be used in chronic studies, which scales to very small nerves.

We designed, fabricated and characterized a flat multi-level diffractive lens (MDL) comprised of only silicon with diameter = 15.2mm, focal length of 19mm, and operating over the longwave infrared (LWIR) spectrum of 8um to 14um. We experimentally demonstrated field of view of 46deg, depth of focus >7mm and wavelength-averaged Strehl ratio of 0.46. All these metrics were comparable to those of a conventional refractive lens. The active device thickness is only 8um and its weight (including the silicon substrate) is less than 0.2g.

Microfabricated silicon nitride cantilever beams, with gold disks and triangles were used to study and quantify residual stresses generated by binding with the thiol end groups of Zika aptamers and then with Zika. Binding with aptamers and Zika generated large tensile residual stresses ~ 53 MPa that deflected the beams and changed their reflective color. It also caused the triangular gold patches to detach from their nitride substrates affecting the substrates' “golden” color. Dynamic measurements of the nitride beams' vibrations were used to measure mass loading by Zika with the sensitivity of 2 kHz/ng. The residual stress built-up due to binding with Zika in excess of 9 × 10 4 Zika/beam caused nitride beams to buckle. Zika-induced residual stress measured using the triangular patches was 96 MPa. Large-scale cellulose acetate beams were then used to observe the residual stresses caused by 20 nm gold layer (0.24 MPa), aptamers (0.3 MPa), and then with Zika (0.5 MPa). Acetate beam displacement was used to “sense” Zika with 2 x 10 -6 μm/Zika sensitivity.

Directional deep brain stimulation (DBS) leads have recently been approved and used in patients, and growing evidence suggests that directional contacts can increase the therapeutic window by redirecting stimulation to the target region while avoiding side-effect-inducing regions. We outline the design, fabrication, and testing of a novel directional DBS lead, the μDBS, which utilizes microscale contacts to increase the spatial resolution of stimulation steering and improve the selectivity in targeting small diameter fibers. We outline the steps of fabrication of the μDBS, from an integrated circuit design to post-processing and validation testing. We tested the onboard digital circuitry for programming fidelity, characterized impedance for a variety of electrode sizes, and demonstrated functionality in a saline bath. In a computational experiment, we determined that reduced electrode sizes focus the stimulation effect on small, nearby fibers. Smaller electrode sizes allow for a relative decrease in small-diameter axon thresholds compared to thresholds of large-diameter fibers, demonstrating a focusing of the stimulation effect within small, and possibly therapeutic, fibers. This principle of selectivity could be useful in further widening the window of therapy. The μDBS offers a unique, multiresolution design in which any combination of microscale contacts can be used together to function as electrodes of various shapes and sizes. Multiscale electrodes could be useful in selective neural targeting for established neurological targets and in exploring novel treatment targets for new neurological indications.

Implantable neural microelectrodes are integral components of neuroprosthetic technologies and can transform treatments for many neural-mediated disorders. However, dielectric material degradation during long-term (> 1 year) indwelling periods restricts device functional lifetimes to a few years. This comprehensive work carefully investigates in vivo material degradation and also explores the ability of in vitro Reactive Accelerated Aging (RAA) to evaluate implant stability. Parylene C-coated Utah electrode arrays (UEAs) implanted in feline peripheral nerve for 3.25 years were explanted and compared to RAA-processed devices, aged in phosphate buffered saline (PBS) + 20 mM H2O2 at either 67 or 87 °C (28 or 7 days, respectively). Electron microscopy revealed similar physical damage characteristics between explants and RAA (87° C) devices. Parylene C degradation was overwhelmingly apparent for UEAs from both RAA cohorts. Controls aged in PBS alone displayed almost no damage. Spectroscopic characterization (EDX, XPS, FTIR) found clear indications of oxidation and chlorine abstraction for parylene C aged in vivo . While in vitro aging was also accompanied by signs of oxidation, changes in the chemistry in vivo and in vitro were statistically different. Analysis of RAA- aged devices identified UEA fabrication approaches that may greatly improve device resistance to degradation. This work underscores the need for an improved understanding of in vivo damage mechanisms, to facilitate the critical need for representative in vitro accelerated testing paradigms for long-term implants.

Long-term neural stimulation and recording efficacy is critical for clinical translation of neural interface technologies for use in therapeutic and diagnostic applications. As part of the DARPA HAPTIX program, we will be performing neural stimulation and recording in peripheral nerves of human subjects for more than 1 year, driving the need to improve the electrode metallization. This motivated the development of aggressive in vitro test to evaluate and improve the electrode material and its electrochemical stability. Utah Electrode Arrays (UEAs) with thin film IrOx electrode sites were pulsed at 1,667 Hz for 10 9 pulses using cathodal-first square biphasic current with 200 µs cathodal and anodal phases, a 100 µs interphase period, and amplitudes ranging from 100 µA to 2,100 µA. The pulse frequency and current werewell outside the typical ranges of 50 to 200 Hz and 1 to 100 µA used for physiological stimulation in order to accelerate failure. The voltage waveforms were sampled, and used in combination with electrochemical impedance spectroscopy and cyclic voltammetry to monitor the electrochemical properties of the electrodes. In addition, physical characterization of the electrodes was performed using back-scattered scanning electron microscopy and dual-beam focused ion beam analysis to investigate changes in surface morphology and the layer structure of the electrodes. Electrodes were stimulated at amplitudes up to 1,600 µA without observable degradation of the electrochemical properties or changes morphology. This stimulation had cathodic excursions (E mc ) up to -2 V, which is well outside the water window. Some electrodes stimulated at amplitudes of 2,100 µA experienced modest degradation, and rarely an electrode was damaged catastrophically, with the majority of the tip metal delaminated. The damaged electrodes were investigated with electron microscopy. The dendritic morphology of the IrOx films was fully preserved except during catastrophic failure where no metal remained to observe. Delamination of the films, ranging from either small regions for the majority of samples to nearly complete metal delamination in rare cases, was observed. This strongly suggests that the IrOx material is highly robust and electrochemically stable during aggressive stimulation testing in-vitro . In addition, with cross-sectional analysis of the tip metal using db-FIB, we observed delamination between the tip metal and silicon electrode. We are investigating if this delamination is occurring through a physical process, or is the result of electrochemical etching of the silicon substrate resulting in undercutting of the electrode. In addition, we have developed a highly sensitive method for electrochemically testing neural electrode dielectric encapsulation. By fully encapsulating devices such that the active electrode region is completely insulated by the dielectric film under investigation, we have been able to resolve the time course and evolution of shunt pathways through dielectric defects with much great sensitivity. The fully encapsulated electrodes are characterized using EIS and current leakage measurements as a function of time to monitor changes in the encapsulation. In addition, electrodes that experience failure as, indicated by leakage currents > 1 nA, were decorated by electrochemical Cu plating to localize failures. Device lifetimes and failure modes characterized by these techniques will be reported.

The new microelectrode array device presented is called PerFlexMEA and it enables controlled coupling between myocytes and nonmyocytes used in cardiovascular conduction studies. The device consists of an 8 μm thin parylene microporous membrane with a 4 × 5 microelectrode array patterned on one side. Myocytes and nonmyocytes can be plated on either side of the parylene membrane to create a tissue bilayer. The 3-3.5 μm diameter pores allow inter-layer dye and electrical coupling without transmembrane cell migration. Cell migration was found to vary with cell-type and micropore diameter. Pore density can be varied based on desired coupling ratio. The flexible parylene membrane is packaged between two rigid thermoplastic layers, such that the microelectrode array region is exposed, while the rest of the device remains insulated. The packaged PerFlexMEA fits in a 60 mm culture dish. Recording experiments are performed by simply plugging it into a commercially available multielectrode amplifier system. Recorded signals were processed and analysed using scripts generated in MATLAB. Our experimental results provide evidence of the reliability of this device, as conduction velocity was observed to decrease after inducing lateral hetero-cellular controlled coupling between myocytes and HeLa cells expressing connexin 43.

Charge-pumping represents an unusual approach to MEMS actuation with the potential benefits of large displacement coupled with high force, as well as simple out-of-plane motions, large-scale self-assembly, simple single contact and even the possibility of non-contact actuation. Charge pumping is conducive to energy scavenging techniques such as tribolectric harvesting, useful in aerospace and satellite applications, but it comes at the cost of modifications to the electronics control infrastructure now based on two-terminal (power/ground) voltage and current paradigms. Non-contact examples will be shown, including devices that can be used for microscale biomimetic optics.

Detection of pathogens and relevant genetic markers using their nucleic acid signatures is extremely common due to the inherent specificity genomic sequences provide. One approach for assaying a sample simultaneously for many different targets is the DNA microarray, which consists of several million short nucleic acid sequences (probes) bound to an inexpensive transparent substrate. Typically, complex samples hybridize to the microarray and the pattern of fluorescing probes on the microarray's surface identifies the detected targets. In the case of evolving or newly emergent organisms, a hybridization pattern can occur that differs from any previously known sources. When this happens it can be useful to recover the hybridized DNA from the binding locations of interest for sequencing. Here we present the novel utilization of a focused Infrared (IR) laser to heat user-selected spots on the DNA microarray surface, causing only localized dehybridization and recovery of the desired DNA into an elution buffer where it is available for subsequent amplification or sequencing. The introduction of a focused dehybridization method for spots of interest suppresses the amount of background DNA to be analyzed from downstream processes, and should reduce subsequent sequence assembly errors. This technique could also be applied to high-density protein microarrays where the desire to locally heat spots for release of bound molecules is desired.

We describe an accommodating lens patterned after the crystalline lens of the eye. Our biomimetic MEMS design calls to mind the zonules of zinn which pull radially to stretch the crystalline lens of the eye to modify the optical path. We present initial characterization of the prototype macro-scale device constructed through traditional machining techniques and using a PDMS polymer lens. Testing of the macro-scale lens indicated a 22% change in focal length through the range of radial stretching, with degradation of the spherical lens shape but no hysteresis after low-cycle testing. We also demonstrate a MEMS implementation of the lens actuator constructed using the Sandia SUMMiT-V (TM) surface micromachining process. The optical path of this system is approximately 300 microns in diameter, providing a platform to potential applications improving mobile camera optics and medical imaging.