skip to main content

Title: Ultrafast laser surgery probe for sub-surface ablation to enable biomaterial injection in vocal folds

Creation of sub-epithelial voids within scarred vocal folds via ultrafast laser ablation may help in localization of injectable therapeutic biomaterials towards an improved treatment for vocal fold scarring. Several ultrafast laser surgery probes have been developed for precise ablation of surface tissues; however, these probes lack the tight beam focusing required for sub-surface ablation in highly scattering tissues such as vocal folds. Here, we present a miniaturized ultrafast laser surgery probe designed to perform sub-epithelial ablation in vocal folds. The requirement of high numerical aperture for sub-surface ablation, in addition to the small form factor and side-firing architecture required for clinical use, made for a challenging optical design. An Inhibited Coupling guiding Kagome hollow core photonic crystal fiber delivered micro-Joule level ultrashort pulses from a high repetition rate fiber laser towards a custom-built miniaturized objective, producing a 1/e2focal beam radius of 1.12 ± 0.10 μm and covering a 46 × 46 μm2scan area. The probe could deliver up to 3.8 μJ pulses to the tissue surface at 40% transmission efficiency through the entire system, providing significantly higher fluences at the focal plane than were required for sub-epithelial ablation. To assess surgical performance, we performed ablation studies on freshly excised porcine hemi-larynges and found that large area sub-epithelial voids could be created within vocal folds by mechanically translating the probe tip across the tissue surface using external stages. Finally, injection of a model biomaterial into a 1 × 2 mm2void created 114 ± 30 μm beneath the vocal fold epithelium surface indicated improved localization when compared to direct injection into the tissue without a void, suggesting that our probe may be useful for pre-clinical evaluation of injectable therapeutic biomaterials for vocal fold scarring therapy. With future developments, the surgical system presented here may enable treatment of vocal fold scarring in a clinical setting.

more » « less
Author(s) / Creator(s):
; ; ; ; ; ; ; ;
Publisher / Repository:
Nature Publishing Group
Date Published:
Journal Name:
Scientific Reports
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Background/Objectives

    Tightly‐focused ultrafast laser pulses (pulse widths of 100 fs–10 ps) provide high peak intensities to produce a spatially confined tissue ablation effect. The creation of sub‐epithelial voids within scarred vocal folds (VFs) via ultrafast laser ablation may help to localize injectable biomaterials to treat VF scarring. Here, we demonstrate the feasibility of this technique in an animal model using a custom‐designed endolaryngeal laser surgery probe.


    Unilateral VF mucosal injuries were created in two canines. Four months later, ultrashort laser pulses (5 ps pulses at 500 kHz) were delivered via the custom laser probe to create sub‐epithelial voids of ~3 × 3‐mm2in both healthy and scarred VFs. PEG‐rhodamine was injected into these voids. Ex vivo optical imaging and histology were used to assess void morphology and biomaterial localization.


    Large sub‐epithelial voids were observed in both healthy and scarred VFs immediately following in vivo laser treatment. Two‐photon imaging and histology confirmed ~3‐mm wide subsurface voids in healthy and scarred VFs of canine #2. Biomaterial localization within a void created in the scarred VF of canine #2 was confirmed with fluorescence imaging but was not visualized during follow‐up two‐photon imaging. As an alternative, the biomaterial was injected into the excised VF and could be observed to localize within the void.


    We demonstrated sub‐epithelial void formation and the ability to inject biomaterials into voids in a chronic VF scarring model. This proof‐of‐concept study provides preliminary evidence towards the clinical feasibility of such an approach to treating VF scarring using injectable biomaterials.

    Level of Evidences

    N/ALaryngoscope, 133:3042–3048, 2023

    more » « less
  2. We present a miniaturized ultrafast laser surgery probe with improved miniaturized optics to deliver higher peak powers and enable higher surgical speeds than previously possible. A custom-built miniaturized CaF2objective showed no evidence of the strong multiphoton absorption observed in our previous ZnS-based probe, enabling higher laser power delivery to the tissue surface for ablation. A Kagome fiber delivered ultrashort pulses from a high repetition rate fiber laser to the objective, producing a focal beam radius of 1.96 μm and covering a 90×90 μm2scan area. The probe delivered the maximum available fiber laser power, providing fluences >6 J/cm2at the tissue surface at 53% transmission efficiency. We characterized the probe’s performance through a parametric ablation study on bovine cortical bone and defined optimal operating parameters for surgery using an experimental- and simulation-based approach. The entire opto-mechanical system, enclosed within a 5-mm diameter housing with a 2.6-mm diameter probe tip, achieved material removal rates >0.1 mm3/min, however removal rates were ultimately limited by the available laser power. Towards a next generation surgery probe, we simulated maximum material removal rates when using a higher power fiber laser and found that removal rates >2 mm3/min could be attained through appropriate selection of laser surgery parameters. With future development, the device presented here can serve as a precise surgical tool with clinically viable speeds for delicate applications such as spinal decompression surgeries.

    more » « less
  3. Abstract

    Biomaterial-enabledde novoformation of non-fibrotic tissue in situ would provide an important tool to physicians. One example application, glottic insufficiency, is a debilitating laryngeal disorder wherein vocal folds do not fully close, resulting in difficulty speaking and swallowing. Preferred management of glottic insufficiency includes bulking of vocal folds via injectable fillers, however, the current options have associated drawbacks including inflammation, accelerated resorption, and foreign body response. We developed a novel iteration of microporous annealed particle (MAP) scaffold designed to provide persistent augmentation. Following a 14-month study of vocal fold augmentation using a rabbit vocal paralysis model, most MAP scaffolds were replaced with tissuede novothat matched the mixture of fibrotic and non-fibrotic collagens of the contralateral vocal tissue. Further, persistent tissue augmentation in MAP-treated rabbits was observed via MRI and via superior vocal function at 14 months relative to the clinical standard.

    more » « less
    more » « less
  5. Lasers are an essential tool in modern medical practice, and their applications span a wide spectrum of specialties. In laryngeal microsurgery, lasers are frequently used to excise tumors from the vocal folds [1]. Several research groups have recently developed robotic systems for these procedures [2-4], with the goal of providing enhanced laser aiming and cutting precision. Within this area of research, one of the problems that has received considerable attention is the automatic control of the laser focus. Briefly, laser focusing refers to the process of optically adjusting a laser beam so that it is concentrated in a small, well-defined spot – see Fig. 1. In surgical applications, tight laser focusing is desirable to maximize cutting efficiency and precision; yet, focusing can be hard to perform manually, as even slight variations (< 1 mm) in the focal distance can significantly affect the spot size. Motivated by these challenges, Kundrat and Schoob [3] recently introduced a technique to robotically maintain constant focal distance, thus enabling accurate, consistent cutting. In another study, Geraldes et al. [4] developed an automatic focus control system based on a miniaturized varifocal mirror, and they obtained spot sizes as small as 380 μm for a CO2 laser beam. Whereas previous work has mainly dealt with the problem of creating – and maintaining – small laser spots, in this paper we propose to study the utility of defocusing surgical lasers. In clinical practice, physicians defocus a laser beam whenever they wish to change its effect from cutting to heating – e.g., to thermally seal a blood vessel [5]. To the best of our knowledge, no previous work has studied the problem of robotically regulating the laser focus to achieve controlled tissue heating, which is precisely the contribution of the present manuscript. In the following sections, we first briefly review the dynamics of thermal laser-tissue interactions and then propose a controller capable of heating tissue according to a prescribed temperature profile. Laser-tissue interactions are generally considered hard to control due to the inherent inhomogeneity of biological tissue [6], which can create significant variability in its thermal response to laser irradiation. In this paper, we use methods from nonlinear control theory to synthesize a temperature controller capable of working on virtually any tissue type without any prior knowledge of its physical properties.

    more » « less