Matjaž Humar

Bioabsorbable polymer optical waveguides for deep-tissue photomedicine.

Advances in photonics have stimulated significant progress in medicine, with many techniques now in routine clinical use. However, the finite depth of light penetration in tissue is a serious constraint to clinical utility. Here we show implantable light-delivery devices made of bio-derived or biocompatible, and biodegradable polymers. In contrast to conventional optical fibres, which must be removed from the body soon after use, the biodegradable and biocompatible waveguides may be used for long-term light delivery and need not be removed as they are gradually resorbed by the tissue. As proof of concept, we demonstrate this paradigm-shifting approach for photochemical tissue bonding (PTB). Using comb-shaped planar waveguides, we achieve a full thickness (>10 mm) wound closure of porcine skin, which represents ∼10-fold extension of the tissue area achieved with conventional PTB. The results point to a new direction in photomedicine for using light in deep tissues.

Photonic hydrogel sensors.

Analyte-sensitive hydrogels that incorporate optical structures have emerged as sensing platforms for point-of-care diagnostics. The optical properties of the hydrogel sensors can be rationally designed and fabricated through self-assembly, microfabrication or laser writing. The advantages of photonic hydrogel sensors over conventional assay formats include label-free, quantitative, reusable, and continuous measurement capability that can be integrated with equipment-free text or image display. This Review explains the operation principles of photonic hydrogel sensors, presents syntheses of stimuli-responsive polymers, and provides an overview of qualitative and quantitative readout technologies. Applications in clinical samples are discussed, and potential future directions are identified.

Step‐Index Optical Fiber Made of Biocompatible Hydrogels

A biocompatible step-index optical fiber made of poly(ethylene glycol) and alginate hydrogels is demonstrated. The fabricated fiber exhibits excellent light-guiding efficiency in biological tissues. Moreover, the core of hydrogel fibers can be easily doped with functional molecules and nanoparticles for localized light emission, sensing, and therapy.

Toward biomaterial-based implantable photonic devices

Abstract Optical technologies are essential for the rapid and efficient delivery of health care to patients. Efforts have begun to implement these technologies in miniature devices that are implantable in patients for continuous or chronic uses. In this review, we discuss guidelines for biomaterials suitable for use in vivo. Basic optical functions such as focusing, reflection, and diffraction have been realized with biopolymers. Biocompatible optical fibers can deliver sensing or therapeutic-inducing light into tissues and enable optical communications with implanted photonic devices. Wirelessly powered, light-emitting diodes (LEDs) and miniature lasers made of biocompatible materials may offer new approaches in optical sensing and therapy. Advances in biotechnologies, such as optogenetics, enable more sophisticated photonic devices with a high level of integration with neurological or physiological circuits. With further innovations and translational development, implantable photonic devices offer a pathway to improve health monitoring, diagnostics, and light-activated therapies.

Cellular dye lasers: lasing thresholds and sensing in a planar resonator

Biological cell lasers are promising novel building blocks of future biocompatible optical systems and offer new approaches to cellular sensing and cytometry in a microfluidic setting. Here, we demonstrate a simple method for providing optical gain by using a variety of standard fluorescent dyes. The dye gain medium can be located inside or outside a cell, or in both, which gives flexibility in experimental design and makes the method applicable to all cell types. Due to the higher refractive index of the cytoplasm compared to the surrounding medium, a cell acts as a convex lens in a planar Fabry-Perot cavity. Its effect on the stability of the laser cavity is analyzed and utilized to suppress lasing outside cells. The resonance modes depend on the shape and internal structure of the cell. As proof of concept, we show how the laser output modes are affected by the osmotic pressure.

Optical lens-microneedle array for percutaneous light delivery

The limited penetration depth of light in skin tissues is a practical bottleneck in dermatologic applications of light-induced therapies, including anti-microbial blue light therapy and photodynamic skin cancer therapy. Here, we demonstrate a novel device, termed optical microneedle array (OMNA), for percutaneous light delivery. A prototype device with a 11 by 11 array of needles at a spacing of 1 mm and a length of 1.6 mm was fabricated by press-molding poly-(lactic acid) (PLA) polymers. The device also incorporates a matched microlens array that focuses the light through the needle tips at specific points to achieve an optimal intensity profile in the tissue. In experiments done with bovine tissues, the OMNA enabled us to deliver a total of 7.5% of the input photons at a wavelength of 491 nm, compared to only 0.85% without the device. This 9-fold enhancement of light delivery was close to the prediction of 10.8 dB by ray-tracing simulation and is expected to increase the effective treatment depth of anti-microbial blue light therapy significantly from 1.3 to 2.5 mm in human skin.

Lasing properties of polymerized chiral nematic Bragg onion microlasers

Dye doped photocurable cholesteric liquid crystal was used to produce solid Bragg onion omnidirectional lasers. The lasers were produced by dispersing and polymerizing chiral nematic LC with parallel surface anchoring of LC molecules at the interface, extracted and transferred into another medium. Lasing characteristics were studied in carrier medium with different refractive index. The lasing in spherical cholesteric liquid crystal was attributed to two mechanisms, photonic bandedge lasing and lasing of whispering-gallery modes. The latter can be suppressed by using a higher index carrier fluid to prevent total internal reflection on the interface of the spheres. Pulse-to-pulse stability and threshold characteristics were also studied and compared to non-polymerized lasers. The polymerization process greatly increases the lasing stability.

Biomaterial microlasers implantable in the cornea, skin, and blood

Stand-alone laser particles that are implantable into biological tissues have potential to enable novel optical imaging, diagnosis and therapy. Here we demonstrate several types of biocompatible microlasers and their lasing action within biological systems. Dye-doped polystyrene beads were embedded in the cornea and optically pumped to generate narrowband emission. We fabricated microbeads with poly(lactic-co-glycolic acid) and poly(lactic acid)-substances approved for medical use-and demonstrate lasing from within tissues and whole blood. Furthermore, we demonstrate biocompatible cholesterol-derivative microdroplet lasers via self-assembly to an onion-like radially-resonant photonic crystal structure.

Whispering-gallery-mode emission from biological luminescent protein microcavity assemblies

Fluorescence and bioluminescence are widely used to study biological systems from molecular to whole organism level. However, their broadband emission is often a bottleneck for sensitive spectral measurements and multiplexing. To overcome the limitation, the emitters can be coupled with optical cavity modes to generate narrowband spectral features. Here we demonstrate several types of emitter-resonator complexes made of fluorescent or bioluminescent proteins and artificially or naturally formed optical resonators. We engineered cells to express green fluorescent protein (GFP) fused with ABHD5, which binds to oil or lipid droplets supporting whispering gallery modes (WGM). The genetically-integrated complexes feature well-defined WGM spectral peaks. We measured WGM peaks from GFP-coated BaTiO3 beads (2.56 μm in diameter) during mitosis. Finally, we demonstrate cavity-enhanced bioluminescence using luciferase-coated beads and biochemical excitation. The ability to tailor spontaneous emission by cavity resonance inside biological systems should have applications in biological sensing, imaging and cell tagging.