Ultra-stable nano-micro bubbles in a biocompatible medium for safe delivery of anti-cancer drugs.

We conducted a series of experimental investigations to generate laser-stimulated millimeter bubbles (MBs) around silver nanoparticles (AgNPs) and thoroughly examined the mechanism of bubble formation within this nanocomposite system. One crucial aspect we explored was the lifetime and kinetics of these bubbles, given that bubbles generated by plasmonic nanoparticles are known to be transient with short durations. Surprisingly, our findings revealed that the achieved lifetime of these MBs extended beyond seven days. This impressive longevity far surpasses what has been reported in the existing literature. Further analysis of the experimental data uncovered a significant correlation between bubble volume and its lifetime. Smaller bubbles demonstrated longer lifetimes compared to larger ones, which provided valuable insights for future applications. The experimental results not only confirmed the validity of our model and simulations but also highlighted essential characteristics, including extended lifetime, matching absorption coefficients, adherence to physical boundary conditions, and agreement with simulated system parameters. Notably, we generated these MBs around functionalized AgNPs in a biocompatible nanocomposite medium by utilizing low-power light excitation. By readily binding potent cancer drugs to AgNPs through simple physical mixing, these medications can be securely encapsulated within bubbles and precisely guided to targeted locations within the human body. This capability to deliver drugs directly to the tumor site, while minimizing contact with healthy tissues, can lead to improved treatment outcomes and reduced side effects, significantly enhancing the quality of life for cancer patients.

Active distance control in multi-capsule endoscopy via closed loop electromagnetic force between capsules.

Capsule endoscopy offers a non-invasive and patient-friendly method for imaging the gastrointestinal tract, boasting superior tissue accessibility compared to traditional endoscopy and colonoscopy. While advances have led to capsules capable of drug delivery, tactile sensing, and biopsy, size constraints often limit a single capsule from having multifunctionality. In response, we introduce multi-capsule endoscopy, where individually ingested capsules, each with unique functionalities, work collaboratively. However, synchronized navigation of these capsules is essential for this approach. In this paper, we present an active distance control strategy using a closed-loop system. This entails equipping one capsule with a sphere permanent magnet and the other with a solenoid. We utilized a Simulink model, incorporating (i) the peristalsis motion on the primary capsule, (ii) a PID controller, (iii) force dynamics between capsules through magnetic dipole approximation, and (iv) position tracking of the secondary capsule. For practical implementation, Hall effect sensors determined the inter-capsule distance, and a PID controller adjusted the solenoid's current to maintain the desired capsule spacing. Our proof-of-concept experiments, conducted on phantoms and ex vivo bovine tissues, pulled the leading capsule mimicking a typical human peristalsis speed of 1 cm/min. Results showcased an inter-capsule distance of 1.94 mm ± 0.097 mm for radii of curvature at 500 mm, 250 mm, and 100 mm, aiming for a 2-mm capsule spacing. For ex vivo bovine tissue, the achieved distance was 0.97 ± 0.28 mm against a target inter-capsule distance of 1 mm. Through the successful demonstration of precise inter-capsule control, this study paves the way for the potential of multi-capsule endoscopy in future research.

Electromagnetically actuated 3D-printed tunable optical slit device.

This paper presents the design, manufacturing, and characterization of a three-dimensional (3D)-printed and electromagnetically actuated adjustable optical slit structure. The device comprises magnet-attached slits connected to the main frame via two springs controlled by external coils. To analyze the forces acting on the springs and simulate the mechanical behavior of the device, we developed both analytical and finite-element models. After fabricating the device using fused deposition, we conducted a series of tests to evaluate its performance. These tests included (1) analyzing the opacity of the slit blade as a function of its thickness, (2) measuring the temperature increase resulting from the power applied to the coils to determine the operable range of the structure, and (3) evaluating the hysteresis, repeatability, and resolution (minimum step) of the device. The experimental works were crucial to assessing the device's practicality and optimizing its performance for specific applications, which reveals a maximum slit width of ∼450µm, with ∼6.4µm step size within this study. Overall, our developed slit device has the potential to be useful in various optics-related laboratories due to its compatibility with conventional 1-inch (25.4 mm) diameter optomechanical mounts, compact form, low power consumption, and rapid prototyping capability with hybrid materials in a cost-friendly fashion, owing to the 3D-printing technology. We discuss an application where the adjustable slit is employed in a combined laser-scanning microscope and a spectrometer, highlighting its versatility and potential for the future.

3D-printed actuator-based beam-steering approach for improved physical layer security in visible light communication.

In this study, we present the design, manufacture, and implementation of a 3D-printed lens scanner-based beam steering for use in visible light communication (VLC) applications. The 5cm×5cm scanner is designed for low-cost 3D printing with fused deposition modeling using polylactic acid. Scanning is facilitated through electromagnetic actuation of the lens frame, carrying a conventional 25 mm lens, from two nearly orthogonal directions. The serpentine spring that connects the lens frame to the external frame is tailored to offer similar spring constants in the directions of actuation and has minimal (<1.5mm) sag due to the mass of the lens. The manufactured actuator was integrated on a miniaturized VLC test bed (70cm×40cm×40cm). Using the test bed, we characterized the applied voltage versus beam displacement behavior of the actuator in the lateral plane and demonstrated beam steering on a moving target with face-recognition feedback. The proposed scheme was targeted to offer an improved security measure in VLC through tracking the legitimate receiver (i.e., via face recognition) and uses the feedback to steer the focused light onto the targeted device. The joint use of focusing and steering features allows for the legitimate receiver to roam within the room while enjoying the improved secrecy due to the focused light. We calculate the secrecy capacity for the demonstrated approach, which compares favorably with a number of jamming, spatial modulation, and beam-forming counterparts. The presented actuator can be used with larger room dimensions, yet upscaling to larger illumination units will require the use of a lens having smaller focus to address a larger total steering angle.

Effect of Heat Level and Expose Time on Denaturation of Collagen Tissues.

INTRODUCTION: The applied heat level and expose time are main issues in certain operations/applications, such as a laser assisted tissue welding, preparation of collagen-based biomaterials (films, implants). Therefore, the precise investigation of these parameters is crucial. The results can serve as a guideline to assess potential effects while maintaining the functionality of the collagen structures. METHODS: Collagen tissues from rat-tail tendon, calfskin, and bones are soaked in buffer solutions, then examined by microscope at different temperature levels. RESULTS: Increase in temperature reduced the microscopically observed collagen crimp contrast for calfskin and rat-tail tendons but not for bone tissues. The contrast level for rat tail tendon decreased down to 80% of its initial value at 37, 157, and 266 s for 70, 65, and 60 °C, respectively. The decrease in the crimp contrast was about only 25% and 2% at 55 and 50 °C after 2 h, respectively. 50% drop in contrast level was occurred for the skin samples at 16, 90, 110 and 1900 s for 70, 65, and 60 °C, respectively. The bone samples, did not show any significant differences in contrast levels. CONCLUSION: The observed denaturation behaviours are in line with Arrhenius Law. This study could be expanded on to other types of tissues at wider temperature ranges to make a guideline for biological/medical processes that radiate heat in order to assess their side effects on collagen and other proteins.

Scanning fiber microdisplay: design, implementation, and comparison to MEMS mirror-based scanning displays.

In this study, we propose a compact, lightweight scanning fiber microdisplay towards virtual and augmented reality applications. Our design that is tailored as a head-worn-display simply consists of a four-quadrant piezoelectric tube actuator through which a fiber optics cable is extended and actuated, and a reflective (or semi-reflective) ellipsoidal surface that relays the moving tip of the fiber onto the viewer's retina. The proposed display, offers significant advantages in terms of architectural simplicity, form-factor, fabrication complexity and cost over other fiber scanner and MEMS mirror counterparts towards practical realization. We demonstrate the display of various patterns with ∼VGA resolution and further provide analytical formulas for mechanical and optical constraints to compare the performance of the proposed scanning fiber microdisplay with that of MEMS mirror-based microdisplays. Also we discuss the road steps towards improving the performance of the proposed scanning fiber microdisplay to high-definition video formats (such as HD1440), which is beyond what has been achieved by MEMS mirror based laser scanning displays.

Kagome fiber based ultrafast laser microsurgery probe delivering micro-Joule pulse energies.

We present the development of a 5 mm, piezo-actuated, ultrafast laser scalpel for fast tissue microsurgery. Delivery of micro-Joules level energies to the tissue was made possible by a large, 31 µm, air-cored inhibited-coupling Kagome fiber. We overcome the fiber's low NA by using lenses made of high refractive index ZnS, which produced an optimal focusing condition with 0.23 NA objective. The optical design achieved a focused laser spot size of 4.5 µm diameter covering a 75 × 75 µm2 scan area in a miniaturized setting. The probe could deliver the maximum available laser power, achieving an average fluence of 7.8 J/cm2 on the tissue surface at 62% transmission efficiency. Such fluences could produce uninterrupted, 40 µm deep cuts at translational speeds of up to 5 mm/s along the tissue. We predicted that the best combination of speed and coverage exists at 8 mm/s for our conditions. The onset of nonlinear absorption in ZnS, however, limited the probe's energy delivery capabilities to 1.4 µJ for linear operation at 1.5 picosecond pulse-widths of our fiber laser. Alternatives like broadband CaF2 crystals should mitigate such nonlinear limiting behavior. Improved opto-mechanical design and appropriate material selection should allow substantially higher fluence delivery and propel such Kagome fiber-based scalpels towards clinical translation.

A 5-mm piezo-scanning fiber device for high speed ultrafast laser microsurgery.

Towards developing precise microsurgery tools for the clinic, we previously developed image-guided miniaturized devices using low repetition rate amplified ultrafast lasers for surgery. To improve the speed of tissue removal while reducing device diameter, here we present a new 5-mm diameter device that delivers high-repetition rate laser pulses for high speed ultrafast laser microsurgery. The device consists of an air-core photonic bandgap fiber (PBF) for the delivery of high energy pulses, a piezoelectric tube actuator for fiber scanning, and two aspheric lenses for focusing the light. Its inline optical architecture provides easy alignment and substantial size reduction to 5 mm diameter as compared to our previous MEMS-scanning devices while realizing improved intensity squared (two-photon) lateral and axial resolutions of 1.16 µm and 11.46 µm, respectively. Our study also sheds light on the maximum pulse energies that can be delivered through the air-core PBF and identifies cladding damage at the input facet of the fiber as the limiting factor. We have achieved a maximum energy delivery larger than 700 nJ at 92% coupling efficiency. An in depth analysis reveals how this value is greatly affected by possible slight misalignments of the beam during coupling and the measured small beam pointing fluctuations. In the absence of these imperfections, self-phase modulation becomes the limiting factor for the maximum energy delivery, setting the theoretical upper bound to near 2 µJ for a 1-m long, 7-µm, air-core PBF. Finally, the use of a 300 kHz repetition rate fiber laser enabled rapid ablation of 150 µm x 150 µm area within only 50 ms. Such ablation speeds can now allow the surgeons to translate the surgery device as fast as ~4 mm/s to continuously remove a thin layer of a 150 µm wide tissue. Thanks to a high optical transmission efficiency of the in-line optical architecture of the device and improved resolution, we could successfully perform ablation of scarred cheek pouch tissue, drilling through a thin slice. With further development, this device can serve as a precise and high speed ultrafast laser scalpel in the clinic.

Parameters affecting ultrafast laser microsurgery of subepithelial voids for scar treatment in vocal folds.

Toward developing a new method for restoring tissue viscoelasticity in scarred vocal folds, we previously proposed a method to localize biomaterials within subepithelial voids ablated using ultrafast laser pulses. The clinical implementation of this method necessitates the quantification of the laser parameters for ablating scarred tissue. Here, we present a comprehensive study of these parameters including ablation threshold and bubble lifetime in healthy and scarred tissues. We also present a new method for extracting tissue-specific ablation threshold and scattering lengths of different tissue layers. This method involves finding the ablation threshold at multiple depths and solving the equations based on Beer's law of light attenuation for each depth to estimate the unknown parameters. Measured threshold fluences were 1.75 J/cm2 for vocal folds and 0.5 J/cm2 for cheek pouches for 3-ps, 776-nm laser pulses. Scarred pouches exhibited 30% lower threshold than healthy pouches, possibly due to the degraded mechanical properties of scarred collagen during wound healing. The analysis of tissue architecture indicated a direct correlation between the ablation threshold and tissue tensile strength and that the bubble lifetime is inversely related to tissue stiffness. Overall, this study sheds light on the required laser parameters for successful implementation of ultrafast laser ablation for phonosurgery.

Sensitivity enhancement of grating interferometer based two-dimensional sensor arrays using two-wavelength readout.

Diffraction gratings integrated with microelectromechanical systems (MEMS) sensors offer displacement measurements with subnanometer sensitivity. However, the sensitivity of the interferometric readout may drop significantly based on the gap between the grating and the reference surface. A two-wavelength (2-λ) readout method was previously tested using a single MEMS sensor for illustrating increased displacement measurement capability. This work demonstrates sensitivity enhancement on a sensor array with large scale parallelization (~20,000 sensors). The statistical representation, which is developed to model sensitivity enhancement within a grating based sensor array, is supported by experimental results using a thermal sensor array. In the experiments, two lasers at different wavelengths (633 and 650 nm) illuminate the thermal sensor array from the backside, time-sequentially. The diffracted first order light from the array is imaged onto a single CCD camera. The target scene is reconstructed by observing the change in the first diffracted order diffraction intensity for both wavelengths. Merging of the data from two measurements with two lasers was performed by taking the larger of the two CCD measurements with respect to the reference image for each sensor. ~30% increase in the average sensitivity was demonstrated for a 160×120 pixel IR sensor array. Proposed architecture is also applicable to a variety of sensing applications, such as parallel biosensing and atomic force microscopy, for improved displacement measurements and enhanced sensitivity.

Fourier optics analysis of grating sensors with tilt errors.

Dynamic diffraction gratings can be microfabricated with precision and offer extremely sensitive displacement measurements and light intensity modulation. The effect of pure translation of the moving part of the grating on diffracted order intensities is well known. This study focuses on the parameters that limit the intensity and the contrast of the interference. The effects of grating duty cycle, mirror reflectivities, sensor tilt and detector size are investigated using Fourier optics theory and Gaussian beam optics. Analytical findings reveal that fringe visibility becomes <0.3 when the optical path variation exceeds half the wavelength within the grating interferometer. The fringe visibility can be compensated by monitoring the interfering portion of the diffracted order light only through detector size reduction in the expense of optical power. Experiments were conducted with a grating interferometer that resulted in an eightfold increase in fringe visibility with reduced detector size, which is in agreement with theory. Findings show that diffraction grating readout principle is not limited to translating sensors but also can be used for sensors with tilt or other deflection modes.

Optical design and imaging performance testing of a 9.6-mm diameter femtosecond laser microsurgery probe.

We present the optical design of a 9.6-mm diameter fiber-coupled probe for combined femtosecond laser microsurgery and nonlinear optical imaging. Towards enabling clinical use, we successfully reduced the dimensions of our earlier 18-mm microsurgery probe by half, while improving optical performance. We use analytical and computational models to optimize the miniaturized lens system for off-axis scanning aberrations. The optimization reveals that the optical system can be aberration-corrected using simple aspheric relay lenses to achieve diffraction-limited imaging resolution over a large field of view. Before moving forward with custom lenses, we have constructed the 9.6-mm probe using off-the-shelf spherical relay lenses and a 0.55 NA aspheric objective lens. In addition to reducing the diameter by nearly 50% and the total volume by 5 times, we also demonstrate improved lateral and axial resolutions of 1.27 µm and 13.5 µm, respectively, compared to 1.64 µm and 16.4 µm in our previous work. Using this probe, we can successfully image various tissue samples, such as rat tail tendon that required 2-3 × lower laser power than the current state-of-the-art. With further development, image-guided, femtosecond laser microsurgical probes such as this one can enable physicians to achieve the highest level of surgical precision anywhere inside the body.

Lamellar grating optimization for miniaturized fourier transform spectrometers.

Microfabricated Lamellar grating interferometers (LGI) require fewer components compared to Michelson interferotemeters and offer compact and broadband Fourier transform spectrometers (FTS) with good spectral resolution, high speed and high efficiency. This study presents the fundamental equations that govern the performance and limitations of LGI based FTS systems. Simulations and experiments were conducted to demonstrate and explain the periodic nature of the interferogram envelope due to Talbot image formation. Simulations reveal that the grating period should be chosen large enough to avoid Talbot phase reversal at the expense of mixing of the diffraction orders at the detector. Optimal LGI grating period selection depends on a number of system parameters and requires compromises in spectral resolution and signal-to-bias ratio (SBR) of the interferogram within the spectral range of interest. New analytical equations are derived for spectral resolution and SBR of LGI based FTS systems.

Measuring local RF heating in MRI: Simulating perfusion in a perfusionless phantom.

PURPOSE: To overcome conflicting methods of local RF heating measurements by proposing a simple technique for predicting in vivo temperature rise by using a gel phantom experiment. MATERIALS AND METHODS: In vivo temperature measurements are difficult to conduct reproducibly; fluid phantoms introduce convection, and gel phantom lacks perfusion. In the proposed method the local temperature rise is measured in a gel phantom at a timepoint that the phantom temperature would be equal to the perfused body steady-state temperature value. The idea comes from the fact that the steady-state temperature rise in a perfused body is smaller than the steady-state temperature increase in a perfusionless phantom. Therefore, when measuring the temperature on a phantom there will be the timepoint that corresponds to the perfusion time constant of the body part. RESULTS: The proposed method was tested with several phantom and in vivo experiments. Instead, an overall average of 30.8% error can be given as the amount of underestimation with the proposed method. This error is within the variability of in vivo experiments (45%). CONCLUSION: With the aid of this reliable temperature rise prediction the amount of power delivered by the scanner can be controlled, enabling safe MRI examinations of patients with implants.