Flexible Probe Research Articles

Skin‐Like Transparent Sensor Sheet for Remote Healthcare Using Electroencephalography and Photoplethysmography

AbstractThe growing demand for efficient home healthcare applications for brain disorder diagnostics and treatment has inspired the development of wearable devices for monitoring brain activity. However, flexible probes that have improved biocompatibility for wearable devices are markedly affected by noise due to contact interface issues. In this study, a stretchable (≤1500% strain) and transparent (over 85% transmittance) biocompatible electrode that steadily adheres to skin is developed to fabricate an imperceptible sheet‐type device that wirelessly records electroencephalograms (EEGs). The multifunctional characteristic of the electrode results from the double‐network structure in an elastomer/conductive additive blend on a metal‐nanowire‐based track, which contributed to EEG monitoring with ultralow noise (≈0.14 µV noise floor) and sleep‐stage classification. Furthermore, the optical transparency enabled camera‐based photoplethysmography to detect pulse waves and blood oxygen saturation without interfering with the light path, which is a crucial factor in realizing a remote healthcare system.

Two-photon endomicroscopy with microsphere-spliced double-cladding antiresonant fiber for resolution enhancement.

We demonstrate a miniature fiber-optic two two-photon endomicroscopy with microsphere-spliced double-cladding antiresonant fiber for resolution enhancement. An easy-to-operate process for fixing microsphere permanently in an antiresonant fiber core, by arc discharge, is proposed. The flexible fiber-optic probe is integrated with a parameter of 5.8 mm × 49.1 mm (outer diameter × rigid length); the field of view is 210 µm, the resolution is 1.3 µm, and the frame rate is 0.7 fps. The imaging ability is verified using ex-vivo mouse kidney, heart, stomach, tail tendon, and in-vivo brain neural imaging.

Measurement of low Reynolds number flow emanating from a Turing pattern microchannel array using a modified Bernoulli equation technique

An experimental investigation of the air flow emanating from a Turing pattern microchannel array into an open atmosphere at very low Reynolds (Re) numbers is presented. As designed, the microchannel structure has channel sizes ranging between 0.6 mm and 1.5 mm with a depth of 0.6 mm. The development of a modified Bernoulli equation analysis method to determine fluid flow speed is introduced. Specifically, a low cost, large (11.11 mm inner diameter) flexible tube probe was employed to measure the fluid total pressure field distribution at a fixed distance from the outlets of the microchannel array. Using subsequent numerical modeling of the outlet-to-tube fluid flow interactions, a flow speed dependent correction factor for the determined dynamic pressure field is proposed. The experimentally measured fluid flow distribution is consistent with the expected flow field pattern obtained by additional computational modeling of flow through and exiting the entire Turing pattern microchannel manifold structure. The pressure measurement and post-processing technique for determining flow velocity may be adapted to a wide range of low-speed (e.g., Re≤100) fluid flow measurement scenarios.

Analytical solutions for flexible circular spiral eddy current array coils inside a conductive tube under different operation modes

The eddy current induction of flexible eddy current array probe composed of thin curved circular spiral coils is studied using the second-order vector potential formalism. The analytical expressions of self-and mutual impedance change of coil array element inside a conductive tube under three standard eddy current array operation modes are derived. They are self-transmitting and receiving, absolute and differential transmit-receive, respectively. Further derivation shows that the coefficient matrices of characteristic equations in these modes are the same regardless of whether the element is placed inside or outside a tube, but the non-homogeneous terms are different. Therefore, the solution to another case can be obtained quickly through the transformation relationship. The experimental results show that the theoretical predictions are consistent with the experiment over the 5 kHz–1 MHz excitation frequency range. At the same time, the real and imaginary part errors of impedance change are analyzed, and the application of small inductance flexible coil in three operation modes is discussed. Finally, these expressions provide academic support for the eddy current testing of pipeline defects and their significance in the inversion of tube electromagnetic properties.

Cleanroom strategies for micro- and nano-fabricating flexible implantable neural electronics.

Implantable electronic neural interfaces typically take the form of probes and are made with rigid materials such as silicon and metals. These have advantages such as compatibility with integrated microchips, simple implantation and high-density nanofabrication but tend to be lacking in terms of biointegration, biocompatibility and durability due to their mechanical rigidity. This leads to damage to the device or, more importantly, the brain tissue surrounding the implant. Flexible polymer-based probes offer superior biocompatibility in terms of surface biochemistry and better matched mechanical properties. Research which aims to bring the fabrication of electronics on flexible polymer substrates to the nano-regime is remarkably sparse, despite the push for flexible consumer electronics in the last decade or so. Cleanroom-based nanofabrication techniques such as photolithography have been used as pattern transfer methods by the semiconductor industry to produce single nanometre scale devices and are now also used for making flexible circuit boards. There is still much scope for miniaturizing flexible electronics further using photolithography, bringing the possibility of nanoscale, non-invasive, high-density flexible neural interfacing. This work explores the fabrication challenges of using photolithography and complementary techniques in a cleanroom for producing flexible electronic neural probes with nanometre-scale features.This article is part of the theme issue 'Advanced neurotechnologies: translating innovation for health and well-being'.

Solid-phase microextraction: a fit-for-purpose technique in biomedical analysis.

Solid-phase microextraction (SPME) possesses unique features that allow it to be used in analyses that would not be possible with traditional sample-preparation methods. The simplicity of SPME protocols and extraction devices makes it a uniform platform for analyzing biological samples, either via the headspace or in direct immersion mode. Furthermore, flexible probe design enables SPME to be applied to target objects of different sizes, offering analysis on a scale ranging “from single cell to living organs”. SPME microfibers are minimally invasive, which enables them to be applied for the spatial and temporal monitoring of target analytes or to assess changes in the entire metabolome or lipidome. Furthermore, SPME permits the capture of the elusive portion of the metabolome, thus complementing exhaustive methods that are biased towards highly abundant and stable species. Significantly, SPME can be interfaced with analytical instrumentation to create a rapid diagnostic tool. However, despite these advantages, SPME has some limitations that must be well-understood and addressed. This paper presents examples of up-to-date applications of SPME, challenges related to particular studies, and future perspectives regarding the application of SPME in biomedical analysis.

Optimization of a flexible fiber-optic probe for epi-mode quantitative phase imaging.

Quantitative oblique back-illumination microscopy (qOBM) is an emerging label-free optical imaging technology that enables 3D, tomographic quantitative phase imaging (QPI) with epi-illumination in thick scattering samples. In this work, we present a robust optimization of a flexible, fiber-optic-based qOBM system. Our approach enables in silico optimization of the phase signal-to-noise-ratio over a wide parameter space and obviates the need for tedious experimental optimization which could easily miss optimal conditions. Experimental validations of the simulations are also presented and sensitivity limits for the probe are assessed. The optimized probe is light-weight (∼40g) and compact (8mm in diameter) and achieves a 2µm lateral resolution, 6µm axial resolution, and a 300µm field of view, with near video-rate operation (10Hz, limited by the camera). The phase sensitivity is <20nm for a single qOBM acquisition (at 10Hz) and a lower limit of ∼3 nm via multi-frame averaging. Finally, to demonstrate the utility of the optimized probe, we image (1) thick, fixed rat brain samples from a 9L gliosarcoma tumor model and (2) freshly excised human brain tissues from neurosurgery. Acquired qOBM images using the flexible fiber-optic probe are in excellent agreement with those from a free-space qOBM system (both in-situ), as well as with gold-standard histopathology slices (after tissue processing).

Flexible Multichannel Neural Probe Developed by Electropolymerization for Localized Stimulation and Sensing

AbstractMiniaturization and minimization of mechanical mismatch in neural probes have been two well‐proven directions in suppressing immune response and improving spatial resolution for neuronal stimulations and recordings. While the high impedance brought by the miniaturization of electrodes has been addressed by using conductive polymers coatings in multiple reports, the stiffness of such coatings remains orders of magnitude higher than that of the brain tissue. Here, a flat neural probe based on a highly flexible microelectrode array with electrodeposited hydrogel coatings poly(2‐hydroxyethyl methacrylate) (pHEMA) and conductive polymer poly(3,4‐ethylenedioxythiophene) polystyrene sulfonate (PEDOT/PSS), with a cross‐section area at only 300 µm × 2.5 µm is presented. The PEDOT/PSS coating provides a low interfacial impedance, and the pHEMA deposition bridges the mechanical mismatch between the probe and the brain tissues. The two layers of polymers modification enhance the signal‐to‐noise ratio and allow the microelectrodes array to be engineered for both recording and stimulation purposes. Besides, in vivo testing of microelectrode arrays implanted in rat hippocampus confirms a high senstivity in neural signal recording and excellent charge injection capacity which can induce long‐term potentiation in neural activities in the hippocampus. The probes provide a robust and low‐cost solution to the brain interfaces problem.

Insertion mechanics of amorphous SiC ultra-micro scale neural probes

Objective. Trauma induced by the insertion of microelectrodes into cortical neural tissue is a significant problem. Further, micromotion and mechanical mismatch between microelectrode probes and neural tissue is implicated in an adverse foreign body response (FBR). Hence, intracortical ultra-microelectrode probes have been proposed as alternatives that minimize this FBR. However, significant challenges in implanting these flexible probes remain. We investigated the insertion mechanics of amorphous silicon carbide (a-SiC) probes with a view to defining probe geometries that can be inserted into cortex without buckling. Approach. We determined the critical buckling force of a-SiC probes as a function of probe geometry and then characterized the buckling behavior of these probes by measuring force–displacement responses during insertion into agarose gel and rat cortex. Main results. Insertion forces for a range of probe geometries were determined and compared with critical buckling forces to establish geometries that should avoid buckling during implantation into brain. The studies show that slower insertion speeds reduce the maximum insertion force for single-shank probes but increase cortical dimpling during insertion of multi-shank probes. Significance. Our results provide a guide for selecting probe geometries and insertion speeds that allow unaided implantation of probes into rat cortex. The design approach is applicable to other animal models where insertion of intracortical probes to a depth of 2 mm is required.

Microwave Ablation for Malignant Central Airway Obstruction: A Pilot Study

Background: Malignant central airway obstruction (CAO) is a debilitating complication of primary lung cancer and pulmonary metastases. Therapeutic bronchoscopy is used to palliate symptoms and/or bridge to further therapy. Microwave ablation (MWA) heats tissue by creating an electromagnetic field around an ablation device. We present a pilot study utilizing endobronchial MWA via flexible bronchoscopy as a novel modality for the management of malignant CAO. Methods: Therapeutic bronchoscopy with a flexible MWA probe was performed in 8 cases. We reviewed tumor size, previous ablative techniques, number of applications, ablation time, amount of energy delivered, rate of successful recanalization, complications, and 30-day follow-up. Results: Successful airway recanalization was achieved in all cases. No complications were noted. In 1 case, tumor in-growth within a silicone stent was ablated with no damage to the stent. Discussion: Endobronchial MWA is a novel technique for tumor destruction while maintaining an airway axis. The oven effect and air gap around a tumor allow for safe and effective tissue devitalization and hemostasis without a thermal effect on structures surrounding the airway.

Research Progress on the Flexibility of an Implantable Neural Microelectrode.

Neural microelectrode is the important bridge of information exchange between the human body and machines. By recording and transmitting nerve signals with electrodes, people can control the external machines. At the same time, using electrodes to electrically stimulate nerve tissue, people with long-term brain diseases will be safely and reliably treated. Young’s modulus of the traditional rigid electrode probe is not matched well with that of biological tissue, and tissue immune rejection is easy to generate, resulting in the electrode not being able to achieve long-term safety and reliable working. In recent years, the choice of flexible materials and design of electrode structures can achieve modulus matching between electrode and biological tissue, and tissue damage is decreased. This review discusses nerve microelectrodes based on flexible electrode materials and substrate materials. Simultaneously, different structural designs of neural microelectrodes are reviewed. However, flexible electrode probes are difficult to implant into the brain. Only with the aid of certain auxiliary devices, can the implant be safe and reliable. The implantation method of the nerve microelectrode is also reviewed.

Scalable batch fabrication of ultrathin flexible neural probes using a bioresorbable silk layer

Flexible intracerebral probes for neural recording and electrical stimulation have been the focus of many research works to achieve better compliance with the surrounding tissue while minimizing rejection. Strategies have been explored to find the best way to insert flexible probes into the brain while maintaining their flexibility once positioned. Here, we present a novel and versatile scalable batch fabrication approach to deliver ultrathin and flexible probes consisting of a silk-parylene bilayer. The biodegradable silk layer, whose degradation time is programmable, provides a temporary and programmable stiffener to allow the insertion of ultrathin parylene-based flexible devices. Our innovative and robust batch fabrication technology allows complete freedom over probe design in terms of materials, size, shape, and thickness. We demonstrate successful ex vivo insertion of the probe with acute high-fidelity recordings of epileptic seizures in field potentials as well as single-unit action potentials in mouse brain slices. Our novel technological solution for implanting ultraflexible devices in the brain while minimizing rejection risks shows high potential for use in both brain research and clinical therapies.

Colocalized, bidirectional optogenetic modulations in freely behaving mice with a wireless dual-color optoelectronic probe

Optogenetic methods provide efficient cell-specific modulations, and the ability of simultaneous neural activation and inhibition in the same brain region of freely moving animals is highly desirable. Here we report bidirectional neuronal activity manipulation accomplished by a wireless, dual-color optogenetic probe in synergy with the co-expression of two spectrally distinct opsins (ChrimsonR and stGtACR2) in a rodent model. The flexible probe comprises vertically assembled, thin-film microscale light-emitting diodes with a lateral dimension of 125 × 180 µm2, showing colocalized red and blue emissions and enabling chronic in vivo operations with desirable biocompatibilities. Red or blue irradiations deterministically evoke or silence neurons co-expressing the two opsins. The probe interferes with dopaminergic neurons in the ventral tegmental area of mice, increasing or decreasing dopamine levels. Such bidirectional regulations further generate rewarding and aversive behaviors and interrogate social interactions among multiple mice. These technologies create numerous opportunities and implications for brain research.

Bimetallic metal-organic framework derived 3D hierarchical NiO/Co3O4/C hollow microspheres on biodegradable garbage bag for sensitive, selective, and flexible enzyme-free electrochemical glucose detection

Hierarchical NiO/Co 3 O 4 /C hollow architectures acquired from metal organic frameworks on biodegradable corn starch bag is exploited as a binder less and flexible electrochemical probe for high performance enzyme-fee glucose sensor. • NiO/Co 3 O 4 /C hollow architectures were prepared using Ni-Co/MOF sacrificial templates. • Impacts of catalyst’s molecular/electronic structures on GEOR are realized with DFT. • Ni 3+ /Co 4+ centres involved glucose electrooxidation mechanism is validated. • NiO/Co 3 O 4 /C/BCSB demonstrated sensitive, selective and flexible glucose detection. • NiO/Co 3 O 4 /C’s competence in real sample glucose sensing is realized with human serum. The hierarchical hollow architectured NiO/Co 3 O 4 /C is developed using the sacrificial template of Ni-Co MOF and the proximity of Ni(II)/Co(II) ions with organic ligand in Ni-Co MOF accelerates the generation of tightly pinned NiO/Co 3 O 4 nanostructures with carbon. The elevated charge-transfer process among the constituents of as-formulated nanocatalysts and their structural and electronic relationship are established with DFT studies. The hollow architecture of NiO/Co 3 O 4 /C exposes both the inner and outer surfaces for an effectual glucose utilization, whilst the carbon interlaced metal nanoparticles and binary metal oxide synergism enumerate, respectively, the continual electron mobility and catalytically active channels, accelerating NiO/Co 3 O 4 /C loaded Biodegradable corn starch bag’s (BCSB) enzyme-free glucose sensing performance in human serum with high sensitivity and selectivity. The consistent flexible glucose electrooxidation acquired for NiO/Co 3 O 4 /C/BCSB under variant bending angles along with other unique concerts establish the bendable, binder-less, stable, reusable, and eco-friendly electrochemical probes for the evolution of revolutionary electrochemical diagnosis devices.

Augmented fluoroscopy guided transbronchial pulmonary microwave ablation using a steerable sheath.

BackgroundTransbronchial microwave ablation (MWA) is a promising novel therapy. Despite advances in bronchoscopy and virtual navigation, real time image guidance of probe delivery is lacking, and distal maneuverability is limited. Cone-beam computed tomography (CBCT) based augmented fluoroscopy guidance using steerable sheaths may help overcome these shortcomings. The aim of this study was to evaluate feasibility and accuracy of augmented fluoroscopy guided transbronchial MWA with a steerable sheath and without a bronchoscope.MethodsIn this prospective study, procedures were performed under general anesthesia. Extra-bronchial lung synthetic targets were placed percutaneously. Target and airways extracted from CBCT, with planned bronchial parking point close to the target were overlaid on live fluoroscopy. Endobronchial navigation was solely performed under augmented fluoroscopy guidance. A 6.5 Fr steerable sheath was parked in the bronchus per plan, and a flexible MWA probe was inserted coaxially then advanced through the bronchus wall towards the target. Final in-target position was confirmed by CBCT. Only one ablation of 100 W-5 min was performed per target. Animals were euthanized and pathology analysis of the lungs was performed.ResultsEighteen targets with a median largest diameter of 9 mm (interquartile range, 7–11 mm) were ablated in 9 pigs. Median needle-target center distance was 2 mm (interquartile range, 0–4 mm), and was higher for lower/middle than for upper lobes [0 mm (interquartile range, 0–4 mm) vs. 4 mm (interquartile range, 3–8 mm), P=0.04]. No severe complications or pneumothorax occurred. Two cases of rib fractures in the ablation zone resolved after medical treatment. Median longest axis of the ablation zone on post-ablation computed tomography was 38 mm (interquartile range, 30–40 mm). Histology showed coagulation necrosis of ablated tissue.ConclusionsTransbronchial MWA under augmented fluoroscopy guidance using a steerable sheath is feasible and accurate.

Simultaneous Evaluation of Permeability and Permittivity Using a Flexible Microstrip Line-Type Probe up to 67 GHz

Complex relative permeability and permittivity were evaluated simultaneously in the band of 100 MHz–67 GHz using a flexible microstrip line-type probe. In principle, the probe can evaluate the permeability and permittivity of electromagnetic materials regardless of size. The measured permeability and permittivity were obtained from the transmission coefficient ( <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$S_{21}$ </tex-math></inline-formula> ). Since <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$S_{21}$ </tex-math></inline-formula> under the infinite magnetic field can be estimated by changing the dc magnetic field stepwise, the magnetic and dielectric signals were separated accurately. The complex permeability and permittivity of a NiZn ferrite sheet (10 mm <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\times10$ </tex-math></inline-formula> mm, 0.1 mm thick) and polytetrafluoroethylene (PTFE) (25 mm <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\times25$ </tex-math></inline-formula> mm, 0.79 mm thick) were evaluated accurately.

Flexible Neural Probes with Optical Artifact-Suppressing Modification and Biofriendly Polypeptide Coating.

The advent of optogenetics provides a well-targeted tool to manipulate neurons because of its high time resolution and cell-type specificity. Recently, closed-loop neural manipulation techniques consisting of optical stimulation and electrical recording have been widely used. However, metal microelectrodes exposed to light radiation could generate photoelectric noise, thus causing loss or distortion of neural signal in recording channels. Meanwhile, the biocompatibility of neural probes remains to be improved. Here, five kinds of neural interface materials are deposited on flexible polyimide-based neural probes and illuminated with a series of blue laser pulses to study their electrochemical performance and photoelectric noises for single-unit recording. The results show that the modifications can not only improve the electrochemical performance, but can also reduce the photoelectric artifacts. In particular, the double-layer composite consisting of platinum-black and conductive polymer has the best comprehensive performance. Thus, a layer of polypeptide is deposited on the entire surface of the double-layer modified neural probes to further improve their biocompatibility. The results show that the biocompatible polypeptide coating has little effect on the electrochemical performance of the neural probe, and it may serve as a drug carrier due to its special micromorphology.

A Versatile Platform for Sensitive and Label-Free Identification of Biomarkers through an Exo-III-Assisted Cascade Signal Amplification Strategy.

The development of a versatile and sensitive analytical biomarker detection platform is important for both early diagnosis and treatment of diseases. In the present study, we propose a novel fluorescence-based, ultrasensitive, and label-free biomarker detection platform. This platform relies on a flexible probe design compatible for multiple biomarker identification and Exo-III enzyme-triggered cascade signal amplification. We have validated that this label-free platform exhibits high sensitivity and specificity. Indeed, this platform exhibited brilliant analytical performance in qualifying a carcinoembryonic antigen and small extracellular vesicles (sEVs). It also shows excellent capability in multiplexing mapping of surface proteins of various cancer-derived sEVs. Therefore, we believe that the proposed sensing platform has great potential for clinical diagnosis and anticancer drug development.

Bridging pico-to-nanonewtons with a ratiometric force probe for monitoring nanoscale polymer physics before damage

Understanding the transmission of nanoscale forces in the pico-to-nanonewton range is important in polymer physics. While physical approaches have limitations in analyzing the local force distribution in condensed environments, chemical analysis using force probes is promising. However, there are stringent requirements for probing the local forces generated before structural damage. The magnitude of those forces corresponds to the range below covalent bond scission (from 200 pN to several nN) and above thermal fluctuation (several pN). Here, we report a conformationally flexible dual-fluorescence force probe with a theoretically estimated threshold of approximately 100 pN. This probe enables ratiometric analysis of the distribution of local forces in a stretched polymer chain network. Without changing the intrinsic properties of the polymer, the force distribution was reversibly monitored in real time. Chemical control of the probe location demonstrated that the local stress concentration is twice as biased at crosslinkers than at main chains, particularly in a strain-hardening region. Due to the high sensitivity, the percentage of the stressed force probes was estimated to be more than 1000 times higher than the activation rate of a conventional mechanophore.

Ultrasonic Inspection for Welds with Irregular Curvature Geometry Using Flexible Phased Array Probes and Semi-Auto Scanners: A Feasibility Study

Pipes of various shapes constitute pipelines utilized in industrial sites. These pipes are coupled through welding, wherein complex curvatures such as a flange, an elbow, a reducer, and a branch pipe are often found. Using phased array ultrasonic testing (PAUT) to inspect weld zones with complex curvatures is faced with different challenges due to parts that are difficult to contact with probes, small-diameter pipes, spatial limitations due to adjacent pipes, nozzles, and sloped shapes. In this study, we developed a flexible PAUT probe (FPAPr) and a semi-automatic scanner that was improved to enable stable FPAPr scanning for securing its inspection data consistency and reproducibility. A mock-up test specimen was created for a flange, an elbow, a reducer, and a branch pipe. Artificial flaws were inserted into the specimen through notch and hole processing, and simulations and verification experiments were performed to verify the performance and field applicability of the FPAPr and semi-automatic scanner.