Compact Probe Research Articles

Ultrathin visible-light OCT endomicroscopy for in vivo ultrahigh-resolution neuroimaging in deep brain

Deep-brain neuroimaging, a task that demands high-resolution imaging techniques for visualizing intricate brain structures, assessing deep-seated disease histopathology, and offering real-time intervention guidance, is challenged by the resolution-depth trade-off of current methods. We propose an optical coherence tomography (OCT) endomicroscopy device for high-resolution in vivo imaging of deep brain microstructures and histopathology. A unique liquid shaping technique enables the direct fabrication of a microlens on the fiber tip of the imaging probe, optimizing imaging performance parameters, such as longitudinal focal shift, focused spot size, and working distance. In addition, a broadband visible-light source enhances axial resolution and OCT imaging contrast. As a result, the first monolithic visible-light OCT (vis-OCT) endomicroscope, with a submillimeter outer diameter (∼0.4 mm), is presented, achieving an ultrahigh resolution of 1.4 μm axial × 4.5 μm transverse in air. This compact probe allows minimally invasive in vivo deep-brain imaging in mice at a depth of 7.2 mm. Key regions in the mouse deep brain, such as the isocortex, corpus callosum, and caudate putamen, were successfully identified using our vis-OCT endomicroscope. In addition, we examined the myeloarchitectures and cytoarchitectures in the isocortex. Our findings demonstrate that the vis-OCT endomicroscope offers enhanced visualization of myelinated axon fibers and nerve fiber bundles compared to its 800 nm counterpart. This vis-OCT endomicroscope, overcoming resolution and imaging depth limitations of conventional methods, offers a novel tool for minimally invasive, ultrahigh-resolution in vivo deep brain neuroimaging.

Sensitivity-enhanced optical fiber probe-type humidity sensor based on CaAlg film

Optical fiber probe-type humidity sensors based on calcium alginate (CaAlg) hydrogel films are proposed. The sensor is based on the Michelson interferometer (MI) and constructed by splicing a tapered multimode fiber (MMF) in the middle of two single-mode fibers (SMFs). One of the 1.5 cm long SMFs is coated with CaAlg hydrogel film and can be regarded as the sensor probe. The sensitivity of the sensor is 0.31015 nm/%RH. The high sensitivity, low temperature crosstalk, compact probe structure, and stability of the sensor allow it to be used for humidity monitoring in a variety of complex environments.

High-precision dynamic axial clearance measurement method based on an all-fiber heterodyne microwave-AMCW with an all-phase tracking algorithm

Rotor-stator axial clearance is critical to the safety and efficiency of major rotating machinery. However, factors such as high-speed rotation, narrow space, high temperature, and vibration present significant challenges for high-precision dynamic measurement of axial clearance. This paper proposes an axial clearance measurement method based on an all-fiber heterodyne microwave amplitude-modulated continuous wave (microwave-AMCW) system combined with an all-phase tracking algorithm, characterized by high precision, wide bandwidth, and a large measurement range. To mitigate environmental influences, a heterodyne all-fiber microwave-AMCW optical path structure is developed, and a compact dual-core fiber sensor probe is designed. The all-phase tracking algorithm is introduced to enhance dynamic precision and expand bandwidth. Additionally, what we believe to be a novel bandwidth test method based on time division multiplexing is proposed to evaluate the system's wide-bandwidth performance. The proposed system's performance is validated through simulations and experiments. The results demonstrate that the system exhibits excellent resistance to environmental interference, with a measurement range up to 24.5 mm and a static precision better than 4.5µm. Dynamic experiments further confirm the algorithm's effectiveness, achieving a precision better than 5.3µm at 100kHz bandwidth. Compared to other clearance measurement algorithms including the Hilbert transform and FFT, the proposed method reduces dynamic error by over 74%.

Feasibility of Monitoring Tissue Properties During Microcirculation Disorder Using a Compact Fiber-Based Probe With Sapphire Tip.

One of the urgent tasks of modern medicine is to detect microcirculation disorder during surgery to avoid possible consequences like tissue hypoxia, ischemia, and necrosis. To address this issue, in this article, we propose a compact probe with sapphire tip and optical sensing based on the principle of spatially resolved diffuse reflectance analysis. It allows for intraoperative measurement of tissue effective attenuation coefficient and its alteration during the changes of tissue condition, caused by microcirculation disorder. The results of experimental studies using (1) a tissue-mimicking phantom based on lipid emulsion and hemoglobin and (2) a model of hindlimb ischemia performed in a rat demonstrated the ability to detect rapid changes of tissue attenuation confirming the feasibility of the probe to sense the stressful exposure. Due to a compact design of the probe, it could be useful for rather wide surgical operations and diagnostic purposes as an auxiliary instrument.

Wavefront shaping and imaging through a multimode hollow-core fiber

Multimode fibers recently emerged as compact minimally-invasive probes for high-resolution deep-tissue imaging. However, the commonly used silica fibers have a relatively low numerical aperture (NA) limiting the spatial resolution of a probe. On top of that, light propagation within the solid core generates auto-fluorescence and Raman background, which interferes with imaging. Here we propose to use a hollow-core fiber to solve these problems. We experimentally demonstrate spatial wavefront shaping at the multimode hollow-core fiber output with tunable high-NA. We demonstrate raster-scan and speckle-based compressive imaging through a multimode hollow-core fiber.

Strategic approaches to enhance efficiency and commercial feasibility of copper-based surface plasmon resonance sensing

Despite enormous progress in the field of surface plasmon resonance (SPR) imaging sensor technology in the past three decades, noble metals like Au and Ag, despite their drawbacks, continue to be the metals of choice for plasmonic sensing layers. The conventional architecture of the SPR sensor based on gold/silver and glass prism hinders scaling, portability, and industrial manufacturing. In this contribution, we present a novel architecture of SPR sensor using copper on polycarbonate prism as a cost-effective, scalable, and mass-producible alternative. Various optimization techniques, such as interface layer, protective encapsulation, and 2D affinity layer are explored to address the challenges related to the practical application of copper in a plasmonic sensor. Our results show that optimized architectures of SPR sensor based on copper has a sensitivity of 235.01°/RIU. From a quantitative analysis of the interrelationships among various performance parameters, we have derived a comprehensive sensing parameter that integrates signal quality and sensitivity. The proposed architecture of the copper based SPR sensor can lead to inexpensive, compact, and handy probes that do not sacrifice accuracy or reliability.

Diagnostic potential of blood plasma longitudinal viscosity measured using Brillouin light scattering

Blood plasma viscosity (PV) is an established biomarker for numerous diseases. Measurement of the shear PV using conventional rheological techniques is, however, time consuming and requires significant plasma volumes. Here, we show that Brillouin light scattering (BLS) and angle-resolved spectroscopy measurements of the longitudinal PV from microliter-sized plasma volumes can serve as a proxy for the shear PV measured using conventional viscometers. This is not trivial given the distinct frequency regime probed and the longitudinal viscosity, a combination of the shear and bulk viscosity, representing a unique material property on account of the latter. We demonstrate this for plasma from healthy persons and patients suffering from different severities of COVID-19 (CoV), which has been associated with an increased shear PV. We further show that the additional information contained in the BLS-measured effective longitudinal PV and its temperature scaling can provide unique insight into the chemical constituents and physical properties of plasma that can be of diagnostic value. In particular, we find that changes in the effective longitudinal viscosity are consistent with an increased suspension concentration in CoV patient samples at elevated temperatures that is correlated with disease severity and progression. This is supported by results from rapid BLS spatial-mapping, angle-resolved BLS measurements, changes in the elastic scattering, and anomalies in the temperature scaling of the shear viscosity. Finally, we introduce a compact BLS probe to rapidly perform measurements in plastic transport tubes. Our results open a broad avenue for PV diagnostics based on the high-frequency effective longitudinal PV and show that BLS can provide a means for its implementation.

High-speed forward-viewing optical coherence tomography probe based on Lissajous sampling and sparse reconstruction.

We present a novel endoscopy probe using optical coherence tomography (OCT) that combines sparse Lissajous scanning and compressed sensing (CS) for faster data collection. This compact probe is only 4 mm in diameter and achieves a large field of view (FOV) of 2.25 mm2 and a 10 mm working distance. Unlike traditional OCT systems that use bulky raster scanning, our design features a dual-axis piezoelectric mechanism for efficient Lissajous pattern scanning. It employs compressive data reconstruction algorithms that minimize data collection requirements for efficient, high-speed imaging. This approach significantly enhances imaging speed by over 40%, substantially improving miniaturization and performance for endoscopic applications.

A Novel Small Form-Factor Handheld Optical Coherence Tomography Probe for Oral Soft Tissue Imaging.

Tissue imaging is crucial in oral cancer diagnostics. Imaging techniques such as X-ray imaging, magnetic resonance imaging, optical coherence tomography (OCT) and computed tomography (CT) enable the visualization and analysis of tissues, aiding in the detection and diagnosis of cancers. A significant amount of research has been conducted on designing OCT probes for tissue imaging, but most probes are either heavy, bulky and require external mounting or are lightweight but straight. This study addresses these challenges, resulting in a curved lightweight, low-voltage and compact handheld imaging probe for oral soft tissue examination. To the best of our knowledge, this is the first curved handheld OCT probe with its shape optimized for oral applications. This probe features highly compact all-fiber optics with a diameter of 125 μm and utilizes innovative central deflection magnetic actuation for controlled beam scanning. To ensure vertical stability while scanning oral soft tissues, the fiber was secured through multiple narrow slits at the probe's distal end. This apparatus was encased in a 3D-printed angular cylinder tube (15 mm outer diameter, 12 mm inner diameter and 160 mm in length, weighing < 20 g). An angle of 115° makes the probe easy to hold and suitable for scanning in space-limited locations. To validate the feasibility of this probe, we conducted assessments on a multi-layered imaging phantom and human tissues, visualizing microstructural features with high contrast.

Exonuclease-iii -propelled DNAzyme cascade for sensitive and reliable cervical cancer related miRNA analysis

MicroRNAs (miRNAs) can serve as biomarkers for early-diagnosis, therapy, and postoperative care of cervical cancer. Sensitive and reliable quantification of miRNA remains a huge challenge due to its low expressing levels and background interference. Herein, we propose a novel exonuclease-III (Exo–III)–propelled DNAzyme cascade for sensitive and high-efficient miRNA analysis. This method involves the engineering of compact DNAzyme hairpin probes, including the H1 probe and H2 probe. The H1 probe is designed with exposed analyte recognition subunits that can specifically recognize target miRNA. This recognition triggers two processes: Exo-iii-assisted target regeneration and successive substrate cleavage catalyzed by DNAzyme. The unique character of Exo-III that catalyzes removal of mononucleotides from the blunt or recessed 3′-OH termini of dsDNA confers the approach with a minimal background signal. The multiple signal cycles provided an abundant signal amplification and consequently, the method exhibited a low limit of detection of 3.12 fM, and a better specificity over several homologous miRNAs. In summary, this powerful Exo-III driven DNAzyme cascaded system offers broader and more adaptable methods for comprehending the activities of miRNA in various biological occurrences.

Hemodynamic Bedside Monitoring Instrument with Pressure and Optical Sensors: Validation and Modality Comparison.

Results from two independent clinical validation studies for measuring hemodynamics at the patient's bedside using a compact finger probe are reported. Technology comprises a barometric pressure sensor, and in one implementation, additionally, an optical sensor for photoplethysmography (PPG) is developed, which can be used to measure blood pressure and analyze rhythm, including the continuous detection of atrial fibrillation. The capabilities of the technology are shown in several form factors, including a miniaturized version resembling a common pulse oximeter to which the technology could be integrated in. Several main results are presented: i) the miniature finger probe meets the accuracy requirements of non-invasive blood pressure instrument validation standard, ii) atrial fibrillation can be detected during the blood pressure measurement and in a continuous recording, iii) a unique comparison between optical and pressure sensing mechanisms is provided, which shows that the origin of both modalities can be explained using a pressure-volume model and that recordings are close to identical between the sensors. The benefits and limitations of both modalities in hemodynamic monitoring are furtherdiscussed.

Balanced-detection interferometric cavity-assisted photothermal spectroscopy via collimating fiber-array integration

This work reports on the implementation of a fiber-array with attached microlenses in the balanced-detection Interferometric Cavity-Assisted Photothermal Spectroscopy (ICAPS) scheme, enabling a highly compact probe laser beam path. The sample probe and the reference beam were coupled into a 1-mm spaced Fabry-Perot interferometer with a parallel beam separation of only 1.25 mm. A quantum cascade laser was used to induce photothermal waves, which were detected via a sample probe beam. A reference probe beam was used to realize balanced detection, allowing for significant noise reduction. The sensor’s metrological figures of merit were evaluated by detection of nitric oxide. For the targeted absorption band centered at 1900.08 cm−1 a 1 σ minimum detection limit of 64 ppbv was achieved with a 1-second integration time. This performance corresponds to a normalized noise equivalent absorption of 5.7 ×10−8 cm−1 W Hz−1/2.

Sensing and Controlling Strategy for Upper Extremity Prosthetics Based on Piezoelectric Micromachined Ultrasound Transducer.

Surface electromyography (sEMG) is currently the primary method for user control of prosthetic manipulation. Its inherent limitations of low signal-to-noise ratio, limited specificity and susceptibility to noise, however, hinder successful implementation. Ultrasound provides a possible alternative, but current systems with medical probes are expense, bulky and non-wearable. This work proposes an innovative prosthetic control strategy based on a piezoelectric micromachined ultrasound transducer (PMUT) hardware system. Two PMUT-based probes were developed, comprising a 23×26 PMUT array and encapsulated in Ecoflex material. These compact and wearable probes represent a significant improvement over traditional ultrasound probes as they weigh only 1.8 grams and eliminate the need for ultrasound gel. A preliminary test of the probes was performed in non-disabled subjects performing 12 different hand gestures. The two probes were placed perpendicular to the flexor digitorum superficialis and brachioradialis muscles, respectively, to transmit/receive pulse-echo signals reflecting muscle activities. Hand gesture was correctly predicted 96% of the time with only these two probes. The adoption of the PMUT-based strategy greatly reduced the required number of channels, amount of processing circuit and subsequent analysis. The probes show promise for making prosthesis control more practical and economical.

Equivalent Circuit Analysis for Optimization of Ground plane in a Compact Co-axial Probe Fed Rectangular Microstrip Antenna

Equivalent Circuit Analysis for Optimization of Ground plane in a Compact Co-axial Probe Fed Rectangular Microstrip Antenna

A flexible permanent magnetic field perturbation testing probe based on through-slot flexible magnetic sheet

In the field of non-destructive testing (NDT), the detection of surface cracks using permanent magnetic field perturbation (PMFP) testing has emerged as a novel approach. It is particularly well-suited for detecting ferromagnetic materials due to its capability to identify open cracks, facilitated by a compact and straightforward probe structure. However, the existing rigid PMFP probes pose challenges in terms of shape-conforming, resulting in large lift-off fluctuations during sweeping, and are prone to wear and tear. Furthermore, their suitability is limited when inspecting specimens with various specifications and irregular shapes. To address these issues, this paper proposes a novel PMFP detection method based on the magnetization of a Flexible Magnetic Sheet (FMS). For further optimization, the machining of a through-slot in the FMS, with the magnetic sensor embedded within, serves to capture the magnetic field perturbation. This configuration is employed for the detection of surface defects. Compared to the conventional PMFP method that relies on rigid permanent magnetization, its flexibility makes the proposed method offer notable advantages such as streamlined processing, lightweight construction, and inherent adaptability to various shapes. Moreover, compared to the traditional PMFP structure where the sensor is placed beneath the permanent magnet, the through-plot FMS design exhibits a larger and more uniform magnetic field. Consequently, this feature significantly improves the signal-to-noise ratio by approximately 30%. The flexible testing method has a high application value and can effectively detect rectangular slots of size 1 mm * 1 mm* 12.5 mm and flat-bottom holes of size Φ2mm* 0.5 mm in pipeline testing.

Glovebox-assisted magnetic force microscope for studying air-sensitive samples in a cryogen-free magnet.

Most known two-dimensional magnets exhibit a high sensitivity to air, making direct characterization of their domain textures technically challenging. Herein, we report on the construction and performance of a glovebox-assisted magnetic force microscope (MFM) operating in a cryogen-free magnet, realizing imaging of the intrinsic magnetic structure of water and oxygen-sensitive materials. It features a compact tubular probe for a 50 mm-diameter variable temperature insert installed in a 12T cryogen-free magnet. A detachable sealing chamber can be electrically connected to the tail of the probe, and its pump port can be opened and closed by a vacuum manipulator located on the top of the probe. This sealing chamber enables sample loading and positioning in the glove box and MFM transfer to the magnet maintained in an inert gas atmosphere (in this case, argon and helium gas). The performance of the MFM is demonstrated by directly imaging the surface (using no buffer layer, such as h-BN) of very air-sensitive van der Waals magnetic material chromium triiodide (CrI3) samples at low temperatures as low as 5K and high magnetic fields up to 11.9T. The system's adaptability permits replacing the MFM unit with a scanning tunneling microscope unit, enabling high-resolution atomic imaging of air-sensitive surface samples.

Wearable optical coherence tomography angiography probe for freely moving mice.

Optical coherence tomography (OCT) is an emerging optical imaging technology that holds great potential in medical and biological applications. Apart from its conventional ophthalmic uses, it has found extensive applications in studying various brain activities and disorders in anesthetized/restricted rodents, with a particular focus on visualizing brain blood vessel morphology and function. However, developing a compact wearable OCT probe for studying the brain activity/disorders in freely moving rodents is challenging due to the requirements for stability and lightweight design. Here, we report a robust wearable OCT probe, which, to the best of our knowledge, is the first wearable OCT angiography probe capable of long-term monitoring of mouse brain blood flow. This wearable imaging probe has a maximum scanning speed of 76 kHz, with a 12 µm axial resolution, 5.5 µm lateral resolution, and a large field of view (FOV) of 4 mm × 4 mm. It offers easy assembly and stable imaging, enabling it to capture brain vessels in freely moving rodents. We tested this probe to monitor cerebral hemodynamics for up to 4 hours during the acute ischemic phase after photothrombotic stroke in mice, highlighting the reliability and long-term stability of our probe. This work contributes to the advancement of wearable biomedical imaging.

Multi-Body Biomarker Entrapment System: An All-Encompassing Tool for Ultrasensitive Disease Diagnosis and Epidemic Screening.

Ultrasensitive identification of biomarkers in biofluids is essential for the precise diagnosis of diseases. For the gold standard approaches, polymerase chain reaction and enzyme-linked immunosorbent assay, cumbersome operational steps hinder their point-of-care applications. Here, a bionic biomarker entrapment system (BioES) is implemented, which employs a multi-body Y-shaped tetrahedral DNA probe immobilized on carbon nanotube transistors. Clinical identification of endometriosis is successfully realized by detecting an estrogen receptor, ERβ, from the lesion tissue of endometriosis patients and establishing a standard diagnosis procedure. The multi-body Y-shaped BioES achieves a theoretical limit of detection (LoD) of 6.74 aM and a limit of quantificationof 141aM in a complex protein milieu. Furthermore, the BioES is optimized into a multi-site recognition module for enhanced binding efficiency, realizing the first identification of monkeypox virus antigen A35R and unamplified detection of circulating tumor DNA of breast cancer in serum. The rigid and compact probe framework with synergy effect enables the BioES to target A35R and DNA with a LoD down to 991 and 0.21aM, respectively. Owing to its versatility for proteins and nucleic acids as well as ease of manipulation and ultra-sensitivity, the BioES can be leveraged as an all-encompassing tool for population-wide screening of epidemics and clinical disease diagnosis.

Feasibility studies of multimodal nonlinear endoscopy using multicore fiber bundles for remote scanning from tissue sections to bulk organs

Here, we report on the development and application of a compact multi-core fiber optical probe for multimodal non-linear imaging, combining the label-free modalities of Coherent Anti-Stokes Raman Scattering, Second Harmonic Generation, and Two-Photon Excited Fluorescence. Probes of this multi-core fiber design avoid moving and voltage-carrying parts at the distal end, thus providing promising improved compatibility with clinical requirements over competing implementations. The performance characteristics of the probe are established using thin cryo-sections and artificial targets before the applicability to clinically relevant samples is evaluated using ex vivo bulk human and porcine intestine tissues. After image reconstruction to counteract the data’s inherently pixelated nature, the recorded images show high image quality and morpho-chemical conformity on the tissue level compared to multimodal non-linear images obtained with a laser-scanning microscope using a standard microscope objective. Furthermore, a simple yet effective reconstruction procedure is presented and demonstrated to yield satisfactory results. Finally, a clear pathway for further developments to facilitate a translation of the multimodal fiber probe into real-world clinical evaluation and application is outlined.

Elastocaloric signatures of symmetric and antisymmetric strain-tuning of quadrupolar and magnetic phases in DyB2C2

The adiabatic elastocaloric effect measures the temperature change of a given system with strain and provides a thermodynamic probe of the entropic landscape in the temperature-strain space. Here, we demonstrate that the DC bias strain-dependence of AC elastocaloric effect allows decomposition of the latter into symmetric (rotation-symmetry-preserving) and antisymmetric (rotation-symmetry-breaking) strain channels, using a tetragonal [Formula: see text]-electron intermetallic DyB[Formula: see text]C[Formula: see text]-whose antiferroquadrupolar order breaks local fourfold rotational symmetries while globally remaining tetragonal-as a showcase example. We capture the strain evolution of its quadrupolar and magnetic phase transitions using both singularities in the elastocaloric coefficient and its jumps at the transitions, and the latter we show follows a modified Ehrenfest relation. We find that antisymmetric strain couples to the underlying order parameter in a biquadratic (linear-quadratic) manner in the antiferroquadrupolar (canted antiferromagnetic) phase, which are attributed to a preserved (broken) global tetragonal symmetry, respectively. The broken tetragonal symmetry in the magnetic phase is further evidenced by elastocaloric strain-hysteresis and optical birefringence. Additionally, within the staggered quadrupolar order, the observed elastocaloric response reflects a quadratic increase of entropy with antisymmetric strain, analogous to the role magnetic field plays for Ising antiferromagnetic orders by promoting pseudospin flips. Our results demonstrate AC elastocaloric effect as a compact and incisive thermodynamic probe into the coupling between electronic degrees of freedom and strain in free energy, which holds the potential for investigating and understanding the symmetry of a wide variety of ordered phases in broader classes of quantum materials.