Kenn R. Oldham

chip) achieve a total mechanical scan angle (MSA) of 112° in slow axis resonance, including 11° of addressable static scan angle, and a total MSA of 15° excited at 3 kHz in the fast axis. A bar and hinge simulation model is introduced that accurately captures nonlinear dynamics. These capabilities are suitable for high frame rates in either Lissajous or raster scan patterns in microendoscope form factors, while static scan angle in bending enables significant 1D addressability.

This paper describes fabrication and preliminary testing results for thin-film lead-zirconate-titanate (PZT) unimorphs arranged in arrays to produce continuous, large deformation bending actuation over millimeter scales. Prototype arrays combine individual thin-film PZT elements into a combined <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$5.2 \text{mm} \times 1.5 \text{mm}$</tex> actuator, capable of over 2 mm of tip displacement at 20 V. A novel polymer reinforcement lattice fabricated through refill of high-aspect ratio silicon trenches is used to maintain a uniform, planar structure in the transverse axis of the array, despite the presence of significant residual stress following micro-fabrication. Actuator displacement and curvature are measures, and effective stiffness and blocking force are estimated based on laminate beam models and dynamic frequency response.

Elevated intracranial pressure (ICP) after traumatic brain injury can impede cerebral blood flow and contribute to secondary ischemic injury. However, direct ICP measurement is currently available only through invasive catheterization in critical care settings, while most tools being studied for noninvasive measurement permit only intermittent. This work examines the use of peripheral blood pressure waveform information to infer changes in ICP with a simple peripheral pressure sensor. Waveforms are reproduced by the direct fitting of a fluid circuit model for arterial and intracranial pressure behavior that was previously developed for use with an intraparenchymal catheter. A regression model is established between mean arterial blood pressure, differential ICP as inferred from the circuit model, and reference ICP measurements from invasive catheterization in eleven hospitalized subjects.

Accurate in vivo staging of early gastrointestinal (GI) cancers is critical for selecting between local and systemic therapy. We present a molecularly targeted photoacoustic endoscopy (PAE) system that combines a compact, fiber-scanning side-view probe with a HER2-targeted near-infrared (NIR) contrast agent (KSP*-IRDye800) to assess mucosal and submucosal tumor invasion in vivo. The 4.2 mm diameter probe uses a piezoelectric (PZT) bender to steer a laser beam laterally (±16°) and achieve high-resolution imaging. The system provides 363 μm lateral and 119 μm axial resolution at a depth of 3.1 mm and supports 3D volumetric image acquisition via rotational scanning and linear pullback. In vivo imaging was performed in CPC;Apc mice that spontaneously develop colonic adenomas. The targeted contrast agent demonstrated a significantly higher peak target-to-background (T/B) ratio (3.0 ± 0.3, RSD = 10%) than indocyanine green (ICG, 1.37 ± 0.1), with peak uptake at 1.5 hours post-injection. Adenoma dimensions measured by PAE correlated strongly with histology (ρ = 0.97 for width, ρ = 0.90 for depth), and 3D reconstructions accurately delineated tumor margins. Ex vivo validation confirmed imaging performance and molecular specificity. This work demonstrates the feasibility of targeted PAE for high-resolution, minimally invasive staging of early GI tumors. The system’s resolution and depth performance are sufficient to distinguish between T1a and T1b lesions. Integration of molecular contrast with miniaturized photoacoustic imaging enables real-time assessment of tumor invasion depth and has potential to improve diagnostic accuracy and therapeutic decision-making during endoscopy.

One of the primary objectives of treatment for acute traumatic brain injury is to prevent subsequent ischemic injury. Reliable cerebral blood flow (CBF) monitoring is desirable for accurate clinical assessments and quick interventions, but existing tools can be complex to apply or available only intermittently. This study introduces two new multimodal approaches for relative CBF tracking based on simple sensing elements. In the first approach, sensors are used to augment an existing minimally-invasive intracranial catheter. In the second approach, sensors are worn non-invasively as a ring. Both consist of a photoplethysmogram blood volume sensor and a piezoelectric-based pressure sensor, which are used to capture local cerebral vascular resistance changes that are rarely available in the existing practice. Sensors are tested with (N=8) swine experiments in which multi-modal signals are collected, followed by data cleaning, feature extraction, and long short-term memory (LSTM) regression analysis to identify CBF information carried by intracranial and/or peripheral waveforms. Reference CBF measurements are collected by transcranial Doppler ultrasound. Results indicate that by combining the photoplethysmogram and piezoelectric sensing, a continuous relative CBF tracking method can be obtained. Alone or in combination, the proposed sensors demonstrate a better estimation of CBP changes than the cerebral perfusion pressure.

This article examines interdependent design of an optical path and a microelectromechanical system (MEMS) scanning mirror for a miniature, implantable fluorescence microscope with large working distance (WD). Linearized and numerical ray analyses are used to approximately decouple optical and mechanical functions during design. We then maximize scan rate in the scenario of high-NA focusing with a specified WD and field-of-view (FOV). To do so, dynamic rotational analysis is combined with a novel model for expected failure voltage of parametrically-resonant electrostatic MEMS scanning mirrors. Mirrors parameters are set to optimize mirror speed within constraints fixed by optical specifications, while compatible optical path is selected for small objective diameter. A prototype instrument achieving sub-cellular resolution up to approximately 500 x 500 μm<sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> FOV at up to 300 μm WD is validated on imaging targets and excised mouse brain tissue.

Large-deformation microactuators, organized in origami-inspired panel/hinge architectures, can be used to construct a variety of mechanisms for small-scale manipulation. In such manipulation applications, it is often desirable to measure the interaction forces that arise between the actuation mechanism and the external object. At the micro-scale, force estimation can be challenging due to device variability, constraints on space for sensor integration, and limited sensing resolution. This paper presents a simulation study applying a model-predictive control architecture with two different penalty mechanisms to disturbance force estimation in a panel-hinge micro-structure. The proposed architecture is found to provide improved performance over Kalman filter-based approaches in the context of limited sensor resolution and sampling rate. The different penalty mechanisms offer different advantages with respect to either model parameters mismatch or output noise. Performance trends with model error are assessed, with discussion of practical considerations for implementation with prototype micro-origami structures.

This work introduces a mixed-transducer micro-origami to achieve efficient vibration, controllable motion, and decoupled sensing. Existing micro-origami systems tend to have only one type of transducer (actuator/sensor), which limits their versatility and functionality because any given transducer system has a narrow range of advantageous working conditions. However, it is possible to harness the benefit of different micro-transducer systems to enhance the performance of functional micro-origami. More specifically, this work introduces a micro-origami system that can integrate the advantages of three transducer systems: strained morph (SM) systems, polymer based electro-thermal (ET) systems, and thin-film lead zirconate titanate (PZT) systems. A versatile photolithography fabrication process is introduced to build this mixed-transducer micro-origami system, and their performance is investigated through experiments and simulation models. This work shows that mixed-transducer micro-origami can achieve power efficient vibration with high frequency, large vibration ranges, and little degradation; can produce decoupled folding motion with good controllability; and can accomplish simultaneous sensing and actuation to detect and interact with external environments and small-scale samples. The superior performance of mixed-transducer micro-origami systems makes them promising tools for micro-manipulation, micro-assembly, biomedical probes, self-sensing metamaterials, and more.

We present an implantable probe utilizing single-pixel confocal microscopy based on a scanning micro- mirror for one-photon brain imaging. Addressing the specific needs of expansive fields of view (FOV) and extended working distances, this multi-wavelength, multi-modal probe achieves a subcellular resolution of 1.5 µm within a FOV of roughly 500 &mu;m and a working distance of 250 &mu;m. Our design integrates off- the-shelf optics with the cost-efficiency of inexpensive 3D printing, offering an affordable and effective imaging tool. A customized oval-shaped electrostatic mirror enhances the imaging capability. Validation, using wavelengths of 445, 515, and 561 nm on both microbeads and Brainbow mice specimens, emphasizes the probe's potential for advancing one-photon brain imaging techniques in freely moving animals. The economic and accessible nature of this tool holds promise for broader applications in neuroscience research.

SignificanceA Fabry–Perot (FP) polymer film sensor can be used to detect acoustic waves in a photoacoustic endoscope (PAE) if the dimensions can be adequately scaled down in size. Current FP sensors have limitations in size, sensitivity, and array configurability.AimWe aim to characterize and demonstrate the imaging performance of a miniature FP sensor to evaluate the effects of reduced size and finite dimensions.ApproachA transfer matrix model was developed to characterize the frequency response of a multilayer miniature FP sensor. An analytical model was derived to describe the effects of a substrate with finite thickness. Finite-element analysis was performed to characterize the temporal response of a sensor with finite dimensions. Miniature 2×2 mm2 FP sensors were designed and fabricated using gold films as reflective mirrors on either side of a parylene C film deposited on a glass wafer. A single-wavelength laser was used to interrogate the sensor using illumination delivered by fiber subprobes. Imaging phantoms were used to verify FP sensor performance, and in vivo images of blood vessels were collected from a live mouse.ResultsThe finite thickness substrate of the FP sensor resulted in echoes in the time domain signal that could be removed by back filtering. The substrate acted as a filter in the frequency domain. The finite lateral sensor dimensions produced side waves that could be eliminated by surface averaging using an interrogation beam with adequate diameter. The fabricated FP sensor produced a noise-equivalent pressure = 0.76 kPa, bandwidth of 16.6 MHz, a spectral full-width at-half-maximum = 0.2886 nm, and quality factor Q=2694. Photoacoustic images were collected from phantoms and blood vessels in a live mouse.ConclusionsA miniature wafer-based FP sensor design has been demonstrated with scaled down form factor for future use in PAE.

While the electrothermal actuators are popular among micro-scale devices, the heat transfer process in electrothermally-actuated micro-origami systems can be geometry-dependent due to the large defections that occur with folding. This paper proposes a thermal model based on thermal conduction for an electrothermally-actuated micro-origami system with structure-dependent thermal resistances and capacitances. The model is compared to experimental results for both static and step responses. After calibration, comparison in the static response suggests that the model is able to capture non-linear behaviors due to large folding of the micro-origami system. Several additional nonlinear behaviors are observed from transient step dynamics that are hypothesized to arise from temperature/strain rate-dependent material nonlinearities. After calibration of material properties and introduction of additional residual stress that is related to the heating rate, the model can closely match the experimental step response behavior. This model may help to control the transient folding process of future micro-origami systems.

Abstract A wide-field endoscope that is sensitive to fluorescence can be used as an adjunct to conventional white light endoscopy by detecting multiple molecular targets concurrently. We aim to demonstrate a flexible fiber-coupled accessory that can pass forward through the instrument channel of standard medical endoscopes for clinical use to collect fluorescence images. A miniature scan mirror with reflector dimensions of 1.30 × 0.45 mm 2 was designed, fabricated, and placed distal to collimated excitation beams at λ ex = 488, 660, and 785 nm. The mirror was driven at resonance for wide angular deflections in the X and Y-axes. A large image field-of-view (FOV) was generated in real time. The optomechanical components were packaged in a rigid distal tip with dimensions of 2.6 mm diameter and 12 mm length. The scan mirror was driven at 27.6 and 9.04 kHz in the fast (X) and slow (Y) axes, respectively, using a square wave with 50% duty cycle at 60 V pp to collect fluorescence images at 10 frames per sec. Maximum total divergence angles of ± 27.4° and ± 22.8° were generated to achieve a FOV of 10.4 and 8.4 mm, respectively, at a working distance of 10 mm. Multiplexed fluorescence images were collected in vivo from the rectum of live mice using 3 fluorescently-labeled peptides that bind to unique cell surface targets. The fluorescence images collected were separated into 3 channels. Target-to-background ratios of 2.6, 3.1, and 3.9 were measured. This instrument demonstrates potential for broad clinical use to detect heterogeneous diseases in hollow organs.

A side-view dual axes confocal endomicroscope is demonstrated that can be inserted repetitively in hollow organs of genetically engineered mice for in vivo real-time imaging in horizontal and vertical planes. Near infrared (NIR) excitation at λ ex = 785 nm was used. A monolithic 3-axis parametric resonance scan mirror was fabricated using micro-electro-mechanical systems (MEMS) technology to perform post-objective scanning in the distal end of a 4.19 mm diameter instrument. Torsional and serpentine springs were designed to “switch” the mode of imaging between vertical and horizontal planes by tuning the actuation frequency. This system demonstrated real-time in-vivo images in horizontal and vertical planes with 310 µm depth and 1.75 and 7.5 µm lateral and axial resolution. Individual cells and discrete mucosal structures could be identified.

This paper introduces a model for nonlinear dynamics of a resonant micro-mirror designed for large-angle circular scanning. The mirror is driven by aluminum nitride thin-films within a chip-scale vacuum package, which permits large scan angles to be achieved at low voltages, but with substantial nonlinearity in the mirror’s dynamic response. A nonlinear mirror model is proposed and analyzed to identify major trends in mirror performance and implications for mirror design. Analysis focuses on coupling between two axes, which has not been closely examined for multi-axis micro-mirrors. Coupling between axes is found to be capable of augmenting scan amplitude or causing mirror response to collapse from a circular scan patter to an ellipse or line scan, depending on relative strength of model parameters. Good agreement is achieved between modeled and experimental micro-mirror response, with scan amplitudes near ± 13 degrees under 1.5 V excitation. [2022-0181]

To improve monitoring of cerebral blood flow and arterial response to clinical interventions following acute traumatic brain injury, we have created a small sensor suite that can be mounted around the diameter of a typical intracranial catheter. This instrument is driven by the need to prevent subsequent ischemic injury after a traumatic brain injury, due to elevated intracranial pressure and compromised cerebral autoregulation. To minimize effects on clinician workflow, our sensors can be integrated into catheters that are currently being used in accordance with accepted standards of care. This paper describes the use of a combination of thin piezoelectric material, a photoplethysmogram, and a long short-term memory regression network to track cerebral blood flow fluctuations. The results show a correlation (R2 = 0.76) between beat-to-beat waveform features collected using our sensor suite and reference blood flow measurements by ultrasound imaging. This method we introduce may help give medical professionals timely data on patients’ cerebral hemodynamic status and how well patients responded to clinical interventions.