Spatially controlled photothermal heating of bladder tissue through single-walled carbon nanohorns delivered with a fiberoptic microneedle device.

Laser-based photothermal therapies for urothelial cell carcinoma (UCC) are limited to thermal ablation of superficial tumors, as treatment of invasive lesions is hampered by shallow light penetration in bladder tissue at commonly used therapeutic wavelengths. This study evaluates the utilization of sharp, silica, fiberoptic microneedle devices (FMDs) to deliver single-walled carbon nanohorns (SWNHs) serving as exogenous chromophores in conjunction with a 1,064-nm laser to amplify thermal treatment doses in a spatially controlled manner. Experiments were conducted to determine the lateral and depth dispersal of SWNHs in aqueous solution (0.05 mg/mL) infused through FMDs into the wall of healthy, inflated, ex vivo porcine bladders. SWNH-perfused bladder regions were irradiated with a free-space, CW, 1,064-nm laser in order to determine the SWNH efficacy as exogenous chromophores within the organ. SWNHs infused at a rate of 50 µL/min resulted in an average lateral expansion rate of 0.36 ± 0.08 cm(2)/min. Infused SWNHs dispersal depth was limited to the urothelium and muscular propria for 50 µL/min infusions of 10 min or less, but dispersed through the entire thickness after a 15-min infusion period. Irradiation of SWNH-perfused bladder tissue with 1,064 nm laser light at 0.95 W/cm(2) over 40 s exhibited a maximum increase of approximately 19 °C compared with an increase of approximately 3 °C in a non-perfused control. The results indicate that these silica FMDs can successfully penetrate into the bladder wall to rapidly distribute SWNHs with some degree of lateral and depth control and that SWNHs may be a viable exogenous chromophore for photothermal amplification of laser-based UCC treatments.

Mechanical strengthening of fiberoptic microneedles using an elastomeric support.

BACKGROUND AND OBJECTIVES: Microneedles made from silica fiberoptics permit transmission and collection of light, which is an important functional advantage over metal or silicon microneedles. This added functionality may enhance or even enable new percutaneous light-based clinical diagnostic and therapeutic procedures. Micron-diameter fiberoptic microneedles, created from solid fibers capable of light emission and detection, are designed to penetrate several millimeters into tissue while minimizing tissue invasion and disruption. The mechanical strength (critical buckling force) of high aspect ratio (length to diameter) microneedles is a potential problem, which has motivated our invention of an elastomeric support device. In this study, we have tested our hypothesis that embedding the microneedles in an elastomeric support medium may increase microneedle critical buckling force. MATERIALS AND METHODS: The critical buckling force of silica microneedles with 55, 70, and 110 µm diameters and 3 mm lengths were measured with and without a surrounding elastomeric support (PDMS, polydimethylsiloxane). These experimental results were compared to theoretical calculations generated by the Rayleigh-Ritz buckling model. The insertion force required to penetrate ex vivo porcine skin was measured for microneedles with 55 and 70 µm diameters. RESULTS: Use of the PDMS support increased critical buckling force for microneedles of 55, 70, and 110 µm diameters by an average of 610%, 290%, and 33%, respectively. Theoretical calculations by the Rayleigh-Ritz model consistently overestimated the experimentally determined strengthening, but correlated highly with the greater enhancement offered to thinner microneedles. Aided by mechanical strengthening, microneedles 55 µm in diameter were able to repeatedly penetrate. CONCLUSIONS: The critical buckling force of microneedles can be increased substantially to allow extremely high-aspect ratio microneedles, 55-110 µm in diameter and 3 mm in length, to penetrate ex vivo porcine skin. By this strengthening method, the safety and reliability of microneedles in potential clinical applications can be considerably enhanced.

Fiberoptic microneedles: novel optical diffusers for interstitial delivery of therapeutic light.

BACKGROUND AND OBJECTIVES: Photothermal therapies have limited efficacy and application due to the poor penetration depth of light inside tissue. In earlier work, we described the development of novel fiberoptic microneedles to provide a means to mechanically penetrate dermal tissue and deliver light directly into a localized target area.This paper presents an alternate fiberoptic microneedle design with the capability of delivering more diffuse, but therapeutically useful photothermal energy. Laser lipolysis is envisioned as a future clinical application for this design. MATERIALS AND METHODS: A novel fiberoptic microneedle was developed using hydrofluoric acid etching of optical fiber to permit diffuse optical delivery. Microneedles etched for 10, 30, and 50 minutes, and an optical fiber control were compared with three techniques. First, red light delivery from the microneedles was evaluated by imaging the reflectance of the light from a white paper.Second, spatial temperature distribution of the paper in response to near-IR light (1,064 nm, 1 W CW) was recorded using infrared thermography. Third, ex vivo adipose tissue response during 1,064 nm, (5 W CW)irradiation was recorded with bright field microscopy. RESULTS: Acid etching exposed a 3 mm length of the fiber core, allowing circumferential delivery of light along this length. Increasing etching time decreased microneedle diameter, resulting in increased uniformity of red and 1,064 nm light delivery along the microneedle axis. For equivalent total energy delivery, thinner microneedles reduced carbonization in the adipose tissue experiments. CONCLUSIONS: We developed novel microscale optical diffusers that provided a more homogeneous light distribution from their surfaces, and compared performance to a flat-cleaved fiber, a device currently utilized in clinical practice. These fiberoptic microneedles can potentially enhance clinical laser procedures by providing direct delivery of diffuse light to target chromophores, while minimizing undesirable photothermal damage in adjacent, non-target tissue.

Effects of Microneedle Design Parameters on Hydraulic Resistance.

Microneedles have been an expanding medical technology in recent years due to their ability to penetrate tissue and deliver therapy with minimal invasiveness and patient discomfort. Variations in design have allowed for enhanced fluid delivery, biopsy collection, and the measurement of electric potentials. Our novel microneedle design attempts to combine many of these functions into a single length of silica tubing capable of both light and fluid delivery terminating in a sharp tip of less than 100 microns in diameter. This manuscript focuses on the fluid flow aspects of the design, characterizing the contributions to hydraulic resistance from the geometric parameters of the microneedles. Experiments consisted of measuring the volumetric flow rate of de-ionized water at set pressures (ranging from 69-621 kPa) through a relevant range of tubing lengths, needle lengths, and needle tip diameters. Data analysis showed that the silica tubing (~150 micron bore diameter) adhered to within ±5% of the theoretical prediction by Poiseuille's Law describing laminar internal pipe flow at Reynolds numbers less than 700. High hydraulic resistance within the microneedles correlated with decreasing tip diameter. The hydraulic resistance offered by the silica tubing preceding the microneedle taper was approximately 1-2 orders of magnitude less per unit length, but remained the dominating resistance in most experiments as the tubing length was >30 mm. These findings will be incorporated into future design permutations to produce a microneedle capable of both efficient fluid transfer and light delivery.

Fiber optic microneedles for transdermal light delivery: ex vivo porcine skin penetration experiments.

Shallow light penetration in tissue has been a technical barrier to the development of light-based methods for in vivo diagnosis and treatment of epithelial carcinomas. This problem can potentially be solved by utilizing minimally invasive probes to deliver light directly to target areas. To develop this solution, fiber optic microneedles capable of delivering light for either imaging or therapy were manufactured by tapering step-index silica-based optical fibers employing a melt-drawing process. Some of the microneedles were manufactured to have sharper tips by changing the heat source during the melt-drawing process. All of the microneedles were individually inserted into ex vivo pig skin samples to demonstrate the feasibility of their application in human tissues. The force on each microneedle was measured during insertion in order to determine the effects of sharper tips on the peak force and the steadiness of the increase in force. Skin penetration experiments showed that sharp fiber optic microneedles that are 3 mm long penetrate through 2 mm of ex vivo pig skin specimens. These sharp microneedles had a minimum average diameter of 73 mum and a maximum tip diameter of 8 mum. Flat microneedles, which had larger tip diameters, required a minimum average diameter of 125 mum in order to penetrate through pig skin samples. Force versus displacement plots showed that a sharp tip on a fiber optic microneedle decreased the skin's resistance during insertion. Also, the force acting on a sharp microneedle increased more steadily compared with a microneedle with a flat tip. However, many of the sharp microneedles sustained damage during skin penetration. Two designs that did not accrue damage were identified and will provide a basis of more robust microneedles. Developing resilient microneedles with smaller diameters will lead to transformative, novel modes of transdermal imaging and treatment that are less invasive and less painful for the patient.