High Penetration Depth Research Articles

A phased array ultrasonic transducer linear sinusoidal driving system for ultrasound neuromodulation

Ultrasound application has been proven to be a promising noninvasive neuromodulation technique due to the high penetration depth, and high focusing properties. Compared to single-element ultrasonic transducers, phased array transducers have the advantages of adjustable focusing targets and higher focusing accuracy, making them more suitable for transcranial neuromodulation technology. However, there is currently limited research on phased array ultrasonic transducer linear sinusoidal driving systems for precise transcranial neuromodulation. This paper develops a new type of phased array linear driving system, using sine wave as input wave, and designs a new OCL-AB power amplifier circuit based on the Output CapitorLess circuit (OCL) and Class-AB circuit. Furthermore, the dedicated input signal generator and focusing control module are designed and combined with the excitation circuit to form a balanced transformerless (BTL) structure to further boost the output voltage. The experimental results show that the 16-channel prototype of the system can meet various parameter requirements for neural regulation under standard mode ±60 V and BTL mode ±120 V output voltage at 100KHz-1 MHz, and has smaller focusing spot and higher frequency accuracy.

Narrow Bandgap Schottky Heterojunction Sonosensitizer with High Electron-Hole Separation Boosted Sonodynamic Therapy in Bladder Cancer.

Sonodynamic therapy (SDT) is applied to bladder cancer (BC) given its advantages of high depth of tissue penetration and nontoxicity due to the unique anatomical location of the bladder near the abdominal surface. However, low electron-hole separation efficiency and wide bandgap of sonosensitizers limit the effectiveness of SDT. This study aims to develop a TiO2-Ru-PEG Schottky heterojunction sonosensitizer with high electron-hole separation and narrow bandgap for SDT in BC. Density functional theory (DFT) calculations and experiments collectively demonstrate that the bandgap of TiO2-Ru-PEG is reduced due to the Schottky heterojunction with the characteristic of crystalline-amorphous interface formed by the deposition of ruthenium (Ru) within the shell layer of TiO2. Thanks to the enhancement of oxygen adsorption and the efficient separation of electron-hole pairs, TiO2-Ru-PEG promotes the generation of reactive oxygen species (ROS) under ultrasound (US) irradiation, resulting in cell cycle arrest and apoptosis of bladder tumor cells. The in vivo results prove that TiO2-Ru-PEG boosted the subcutaneous and orthotopic bladder tumor models while exhibiting good safety. This study adopts the ruthenium complex for optimizing sonosensitizers, contributing to the progress of SDT improvement strategies and presenting a paradigm for BC therapy.

Photodynamic therapy with redaporfin activated by pulsed laser light

SignificanceRedaporfin is a photosensitizer under clinical trials for head and neck cancer. In previous work, a continuous light source was used in several tumor models, either in vitro or in vivo. However, the use of pulsed light (PL) sources can bring advantages to photodynamic therapy, such as higher penetration depths. ApproachTo study the influence of the light source in the efficacy of redaporfin-PDT, balb/c mice were inoculated with subcutaneous CT26 tumors. Redaporfin was activated using a PL source at 750 nm, with a repetition rate of 20 Hz and an energy per pulse of 24 mJ/cm2. Illumination time ranged from 5 to 15 min. ResultsThe results show an acute inflammatory response followed by a fast shrinkage and necrosis of the tumors and no significant side effects. ConclusionsThe activation of redaporfin with PL leads to good response of the tumors and further studies are being held to optimize the treatment conditions.

Metallurgical and mechanical properties evaluation of the activated flux tungsten inert gas weldments

The activated flux tungsten inert gas welding process is an attractive joining technique to increase the depth of penetration in a single pass. In the last two decades, the research on activated flux tungsten inert gas welding increased drastically. Despite enhanced weld penetration, activated flux tungsten inert gas is not frequently implemented in industries because of a lack of information about the process. However, research on activated flux tungsten inert gas welding has significantly increased in the last decade due to the widespread information related to the advancements in weld penetration and mechanical properties of the activated flux tungsten inert gas process. The activated flux tungsten inert gas welding process provides a high single pass depth of penetration along with good mechanical properties compared to the tungsten inert gas welding process. The current work offers an in-depth analysis of the activated flux tungsten inert gas welding process mechanism, advancement in activated flux tungsten inert gas methodology to improve weld bead geometry, and mechanical and corrosion behaviour of the weldments. The current work also highlights recent progress made in the field of dissimilar metal joining using the activated flux tungsten inert gas welding process.

Modification of a desktop FFF printer via NIR laser addition for upconversion 3D printing

Traditional photopolymer-based 3D printing methods require sequential printing of thin layers, due to short penetration depths of UV or blue light sources used by these techniques. In contrast, upconversion 3D printing circumvents the layer-by-layer limitation by taking advantage of upconversion luminescence processes and the high penetration depths offered by near-infrared (NIR) lasers, allowing for selective crosslinking of voxels at any depth or position within the resin container. The implementation of this technique required the construction of a 3D printer with the ability of focusing the laser on any point of the space. For this, a low-cost fused filament fabrication (FFF) printer was modified by incorporating a 980 nm laser and laser control circuit. The total cost of the parts required for modification was £180. With enhanced penetration depths up to 5.8 cm, this method also allows for printing inside or through existing 3D printed parts. This opens doors for restoration of broken items, in situ bioprinting, 3D-circuitry, and notably, 3D printing inside cavities of a different material, illustrating numerous opportunities for practical applications.

Mimicking Motor Proteins: Wall-Guided Self-Navigation of Microwheels.

Untethered micro/nanorobots (MNRs) show great promise in biomedicine. However, high-precision targeted in vivo navigation of MNRs into both deep and tiny microtube networks comes with big challenges because the present medical imaging cannot simultaneously meet the requirements of high resolution, high penetration depth, and high real-time performance. Inspired by intracellular motor proteins that transport cargo along cytoskeletal tracks, this study proposed a microtube inwall-guided targeted self-navigation strategy of magnetic microwheels (μ-wheels) that relies only on interactions with a microtube inwall, compared to conventional techniques that rely on real-time imaging and tracking of MNRs. By presetting the direction of the rotating magnetic field, the μ-wheel realized targeted navigation along the inwall. The propulsion principles behind it are elaborated. The targeted self-navigation of the μ-wheels in three-dimensional microtube networks, a spiral microtube, and an intrahepatic bile duct of a pig was conducted. Lastly, based on the strategy, a practical tumor early detection method was proposed and verified by means of magnetic resonance imaging. The microtube inwall-guided targeted self-navigation strategy reduces the dependence of in vivo targeted navigation of MNRs on the real-time performance of medical imaging technology and greatly contributes to the development of MNRs in biomedical applications.

Rational Design of NIR-II Ratiometric Fluorescence Probes for Accurate Bioimaging and Biosensing In Vivo.

Intravital fluorescence imaging in the second near-infrared window (NIR-II, 900-1700nm) has emerged as a promising method for non-invasive diagnostics in complex biological systems due to its advantages of less background interference, high tissue penetration depth, high imaging contrast, and sensitivity. However, traditional NIR-II fluorescence imaging, which is characterized by the "always on" or "turn on" mode, lacks the ability of quantitative detection, leading to low reproducibility and reliability during bio-detection. In contrast, NIR-II ratiometric fluorescence imaging can realize quantitative and reliable analysis and detection in vivo by providing reference signals for fluorescence correction, generating new opportunities and prospects during in vivo bioimaging and biosensing. In this review, the current design strategies and sensing mechanisms of NIR-II ratiometric fluorescence probes for bioimaging and biosensing applications are systematically summarized. Further, current challenges, future perspectives and opportunities for designing NIR-II ratiometric fluorescence probes are also discussed. It is hoped that this review can provide effective guidance for the design of NIR-II ratiometric fluorescence probes and promote its adoption in reliable biological imaging and sensing in vivo.

In Silico Analysis of Natural Plant-Derived Cyclotides with Antifungal Activity against Pathogenic Fungi.

Fungal infections in plants, animals, and humans are widespread across the world. Limited classes of antifungal drugs to treat fungal infections and loss of drug efficacy due to rapidly evolving fungal strains pose a challenge in the agriculture and health sectors. Hence, the search for a new class of antifungal agents is imperative. Cyclotides are cyclic plant peptides with multiple bioactivities, including antifungal activity. They have six conserved cysteine residues forming three disulfide linkages (CI-CIV, CII-CV, CIII-CVI) that establish a Cyclic Cystine Knot (CCK) structure, making them extremely resistant to chemical, enzymatic, and thermal attacks. This in silico analysis of natural, plant-derived cyclotides aimed to assess the parameters that can assist and hasten the process of selecting the cyclotides with potent antifungal activity and prioritize them for in vivo/ in vitro experiments. The objective of this study was to conduct in silico studies to compare the physicochemical parameters, sequence diversity, surface structures, and membrane-cyclotide interactions of experimentally screened (from literature survey) potent (MIC ≤ 20 μM) and non-potent (MIC > 20 μM) cyclotides for antifungal activity. Cyclotide sequences assessed for antifungal activity were retrieved from the database (Cybase). Various online and offline tools were used for sequence-based studies, such as physicochemical parameters, sequence diversity, and neighbor-joining trees. Structure-based studies involving surface structure analysis and membrane-cyclotide interaction were also carried out. All investigations were conducted in silico. Physicochemical parameter values, viz. isoelectric point, net charge, and the number of basic amino acids, were significantly higher in potent cyclotides compared to non-potent cyclotides. The surface structure of potent cyclotides showed a larger hydrophobic patch with a higher number of hydrophobic amino acids. Furthermore, the membrane-cyclotide interaction studies of potent cyclotides revealed lower transfer free energy (ΔG transfer) and higher penetration depth into fungal membranes, indicating higher binding stability and membrane-disruption ability. These in silico studies can be applied for rapidly identifying putatively potent antifungal cyclotides for in vivo and in vitro experiments, which will ultimately be relevant in the agriculture and pharmaceutical sectors.

Thin flexible photoacoustic endoscopic probe with a distal-driven micro-step motor for pump-probe-based high-specific molecular imaging.

Conventional photoacoustic endoscopy (PAE) is mostly for structural imaging, and its molecular imaging ability is quite limited. In this work, we address this issue and present the development of a flexible acoustic-resolution-based photoacoustic endoscopic (AR-PAE) probe with an outer diameter of 8 mm. This probe is driven by a micro-step motor at the distal end, enabling flexible and precise angular step control to synchronize with the optical parametric oscillator (OPO) lasers. This probe retains the high spatial resolution, high penetration depth, and spectroscopic imaging ability of conventional AR-PAE. Moreover, it is capable for background-free high-specific photoacoustic molecular imaging with a novel pump-probe detection technique, as demonstrated by the distribution visualizing of the FDA approved contrast agent methylene blue (MB) in an ex-vivo pig ileum. This proposed method represents an important technical advancement in multimodal PAE, and can potentially make considerable contributions across various biomedical fields.

Defect‐Repaired g‐C3N4 Nanosheets: Elevating the Efficacy of Sonodynamic Cancer Therapy Through Enhanced Charge Carrier Migration

AbstractSonodynamic therapy (SDT) has garnered growing interest owing to its high tissue penetration depth and minimal side effects. However, the lack of efficient sonosensitizers remains the primary limiting factor for the clinical application of this treatment method. Here, defect‐repaired graphene phase carbon nitride (g‐C3N4) nanosheets are prepared and utilized for enhanced SDT in anti‐tumor treatment. After defect engineering optimization, the bulk defects of g‐C3N4 are significantly reduced, resulting in higher crystallinity and exhibiting a polyheptazine imide (PHI) structure. Due to the more extended conjugated structure of PHI, facilitating faster charge transfer on the surface, it exhibits superior SDT performance for inducing apoptosis in tumor cells. This work focuses on introducing a novel carbon nitride nanomaterial as a sonosensitizer and a strategy for optimizing sonosensitizer performance by reducing bulk defects.

Defect-Repaired g-C3N4 Nanosheets: Elevating the Efficacy of Sonodynamic Cancer Therapy Through Enhanced Charge Carrier Migration.

Sonodynamic therapy (SDT) has garnered growing interest owing to its high tissue penetration depth and minimal side effects. However, the lack of efficient sonosensitizers remains the primary limiting factor for the clinical application of this treatment method. Here, defect-repaired graphene phase carbon nitride (g-C3N4) nanosheets are prepared and utilized for enhanced SDT in anti-tumor treatment. After defect engineering optimization, the bulk defects of g-C3N4 are significantly reduced, resulting in higher crystallinity and exhibiting a polyheptazine imide (PHI) structure. Due to the more extended conjugated structure of PHI, facilitating faster charge transfer on the surface, it exhibits superior SDT performance for inducing apoptosis in tumor cells. This work focuses on introducing a novel carbon nitride nanomaterial as a sonosensitizer and a strategy for optimizing sonosensitizer performance by reducing bulk defects.

Carboxyl-Modified Quantum Dots for NIR-IIb Bone Marrow Imaging.

Real-time, noninvasive, and nonradiative bone imaging can directly visualize bone health but requires bone-targeted probes with high specificity. Herein, we propose that carboxyl-rich fluorescent nanoprobes are easily absorbed by macrophages in bone marrow during circulation, enabling optical bone marrow imaging in vivo. We used PbS/CdS core-shell quantum dots with NIR-IIb (1500-1700 nm) emission as substrates to prepare the carboxyl-rich nanoprobe. In vivo NIR-IIb fluorescence imaging with the nanoprobes showed high resolution and penetration depth in bone tissues and allowed for imaging-guided fracture diagnosis. Bone tissue slices showed substantial accumulation of carboxyl nanoprobes in the bone marrow and strong colocalization with macrophages. Similar results with CdSe quantum dots and an organic nanofluorophore suggest that carboxyl surface modification is effective to achieve bone marrow targeting, providing a novel strategy for developing bone/bone marrow imaging probes.

Mechanochemical Activation of DNAzyme by Ultrasound.

Controlling the activity of DNAzymes by external triggers is an important task. Here a temporal control over DNAzyme activity through a mechanochemical pathway with the help of ultrasound (US) is demonstrated. The deactivation of the DNAzyme is achieved by hybridization to a complementary strand generated through rolling circle amplification (RCA), an enzymatic polymerization process. Due to the high molar mass of the resulting polynucleic acids, shear force can be applied on the RCA strand through inertial cavitation induced by US. This exerts mechanical force and leads to the cleavage of the base pairing between RCA strand and DNAzyme, resulting in the recovery of DNAzyme activity. This is the first time that this release mechanism is applied for the activation of catalytic nucleic acids, and it has multiple advantages over other stimuli. US has higher penetration depth into tissues compared to light, and it offers a more specific stimulus than heat, which has also limited use in biological systems due to cell damage caused by hyperthermia. This approach is envisioned to improve the control over DNAzyme activity for the development of reliable and specific sensing applications.

Noninvasive neuromodulation of subregions of the human insula differentially affect pain processing and heart-rate variability: a within-subjects pseudo-randomized trial.

The insula is an intriguing target for pain modulation. Unfortunately, it lies deep to the cortex making spatially specific noninvasive access difficult. Here, we leverage the high spatial resolution and deep penetration depth of low-intensity focused ultrasound (LIFU) to nonsurgically modulate the anterior insula (AI) or posterior insula (PI) in humans for effect on subjective pain ratings, electroencephalographic (EEG) contact heat-evoked potentials, as well as autonomic measures including heart-rate variability (HRV). In a within-subjects, repeated-measures, pseudo-randomized trial design, 23 healthy volunteers received brief noxious heat pain stimuli to the dorsum of their right hand during continuous heart-rate, electrodermal, electrocardiography and EEG recording. Low-intensity focused ultrasound was delivered to the AI (anterior short gyrus), PI (posterior longus gyrus), or under an inert Sham condition. The primary outcome measure was pain rating. Low-intensity focused ultrasound to both AI and PI similarly reduced pain ratings but had differential effects on EEG activity. Low-intensity focused ultrasound to PI affected earlier EEG amplitudes, whereas LIFU to AI affected later EEG amplitudes. Only LIFU to the AI affected HRV as indexed by an increase in SD of N-N intervals and mean HRV low-frequency power. Taken together, LIFU is an effective noninvasive method to individually target subregions of the insula in humans for site-specific effects on brain biomarkers of pain processing and autonomic reactivity that translates to reduced perceived pain to a transient heat stimulus.

Laser Beam Welding under Vacuum of Hot-Dip Galvanized Constructional Steel

Hot-dip galvanized components offer a great potential for corrosion protection of up to 100 years, while laser beam welding in vacuum (LaVa) has the advantage of high penetration depths Combined, this process chain can be economically used in steel construction of bridges, wind turbines, or other steel constructions. Therefore, investigations of butt joint welding of galvanized 20 mm thick S355M steel plates using LaVa were carried out. The butt joints were prepared under different cutting edges such as flame-cut, sawn, and milled edges, and they were studied with and without the zinc layer in the joint gap. For this purpose, the laser parameters such as the beam power, welding speed, focus position, and working pressure all varied, as did the oscillation parameters. The welds performed using an infinity oscillation with an amplitude of 5 mm represented a pore-free weld up to a zinc layer thickness of 400 µm in the joint gap. The seam undercut increased with increasing the zinc layer thickness in the joint gap, which can be explained by the evaporating zinc and consequently the missing material, since no filler material was used. The joint welds with zinc only on the sheet surface achieved a sufficient weld quality without pores.

Five near-infrared-emissive graphene quantum dots for multiplex bioimaging

Due to high tissue penetration depth and low autofluorescence backgrounds, near-infrared (NIR) fluorescence imaging has recently become an advantageous diagnostic technique used in a variety of fields. However, most of the NIR fluorophores do not have therapeutic delivery capabilities, exhibit low photostabilities, and raise toxicity concerns. To address these issues, we developed and tested five types of biocompatible graphene quantum dots (GQDs) exhibiting spectrally-separated fluorescence in the NIR range of 928–1053 nm with NIR excitation. Their optical properties in the NIR are attributed to either rare-earth metal dopants (Ho-NGQDs, Yb-NGQDs, Nd-NGQDs) or defect-states (nitrogen doped GQDS (NGQDs), reduced graphene oxides) as verified by Hartree-Fock calculations. Moderate up to 1.34% quantum yields of these GQDs are well-compensated by their remarkable >4 h photostability. At the biocompatible concentrations of up to 0.5–2 mg ml−1 GQDs successfully internalize into HEK-293 cells and enable in vitro imaging in the visible and NIR. Tested all together in HEK-293 cells five GQD types enable simultaneous multiplex imaging in the NIR-I and NIR-II shown for the first time in this work for GQD platforms. Substantial photostability, spectrally-separated NIR emission, and high biocompatibility of five GQD types developed here suggest their promising potential in multianalyte testing and multiwavelength bioimaging of combination therapies.

Fluorescence-Recovered Wearable Hydrogel Patch for In Vitro Detection of Glucose Based on Rare-Earth Nanoparticles.

The physiological state of the human body can be indicated by analyzing the composition of sweat. In this research, a fluorescence-recovered wearable hydrogel patch has been designed and realized which can noninvasively monitor the glucose concentration in human sweat. Rare-earth nanoparticles (RENPs) of NaGdF4 doped with different elements (Yb, Er, and Ce) are synthesized and optimized for better luminescence in the near-infrared second (NIR-II) and visible region. In addition, RENPs are coated with CoOOH of which the absorbance has an extensive peak in the visible and NIR regions. The concentration of H2O2 in the environment can be detected by the fluorescence recovery degree of CoOOH-modified RENPs based on the fluorescence resonance energy transfer effect. For in vivo detection, the physiological state of oxidative stress at tumor sites can be visualized through its fluorescence in NIR-II with low background noise and high penetration depth. For the in vitro detection, CoOOH-modified RENP and glucose oxidase (GOx) were doped into a polyacrylamide hydrogel, and a patch that can emit green upconversion fluorescence under a 980 nm laser was prepared. Compared with the conventional electrochemical detection method, the fluorescence we presented has higher sensitivity and linear detection region to detect the glucose. This improved anti-interference sweat patch that can work in the dark environment was obtained, and the physiological state of the human body is conveniently monitored, which provides a new facile and convenient method to monitor the sweat status.

Preparation of rare earth-doped nano-fluorescent materials in the second near-infrared region and their application in biological imaging.

Second near-infrared (NIR-II) fluorescence imaging (FLI) has gained widespread interest in the biomedical field because of its advantages of high sensitivity and high penetration depth. In particular, rare earth-doped nanoprobes (RENPs) have shown completely different physical and chemical properties from macroscopic substances owing to their unique size and structure. This paper reviews the synthesis methods and types of RENPs for NIR-II imaging, focusing on new methods to enhance the luminous intensity of RENPs and multi-band imaging and multi-mode imaging of RENPs in biological applications. This review also presents an overview of the challenges and future development prospects based on RENPs in NIR-II regional bioimaging.

Near-infrared fluorescence probes based on disassembly-induced emission pyrene derivatives

The fluorescence emission included near infrared and was significantly enhanced (50 times) by co-assembly with cucurbit[8]uril.

Miniaturized photoacoustic/ultrasound endoscopic imaging probe for molecular imaging of deep tissues

Colorectal cancer is one of the leading causes of cancer-related deaths worldwide. Traditional gastrointestinal endoscopes for colorectal cancer mainly rely on optical endoscope and ultrasound endoscope. Owing to significant light scattering in tissues the optical endoscope is limited to superficial tissue imaging, while the ultrasound endoscope, despite deeper penetration, provides limited molecular imaging capabilities. In this work, we build a miniaturized handheld photoacoustic/ultrasound dual-modality endoscopic probe to address these problems. It has a small size of 8 mm, and presents the dual advantages of high penetration depth and superior molecular imaging capability, marking a significant advancement over traditional methods. Results show that this probe achieves a high lateral resolution of 345 μm for photoacoustic imaging and 185 μm for ultrasound imaging at a depth of 12 mm within tissues. It also exhibits the ability to effectively image complex structural targets, as demonstrated by the imaging of a phantom with an embedded metal mesh. Furthermore, the probe adopts an innovative pump-probe method, which effectively mitigates interference from blood and other background tissues, thereby achieving high-specificity photoacoustic molecular imaging. This ability is first confirmed by imaging the distribution of methylene blue (MB) in a phantom, and then by observing the distribution of MB in the depth of tumor in mice. This handheld photoacoustic/ultrasound endoscopic probe has the advantages of small size, high penetration depth, high spatial resolution, and superior molecular imaging ability, and is expected to become an important diagnostic tool for colorectal cancer and other gastrointestinal cancer. This study can provide strong support for early diagnosis and treatment monitoring, potentially revolutionizing the detection and management of these diseases.