Gerd Keiser

Review of diverse optical fibers used in biomedical research and clinical practice

Optical fiber technology has significantly bolstered the growth of photonics applications in basic life sciences research and in biomedical diagnosis, therapy, monitoring, and surgery. The unique operational characteristics of diverse fibers have been exploited to realize advanced biomedical functions in areas such as illumination, imaging, minimally invasive surgery, tissue ablation, biological sensing, and tissue diagnosis. This review paper provides the necessary background to understand how optical fibers function, to describe the various categories of available fibers, and to illustrate how specific fibers are used for selected biomedical photonics applications. Research articles and vendor data sheets were consulted to describe the operational characteristics of conventional and specialty multimode and single-mode solid-core fibers, double-clad fibers, hard-clad silica fibers, conventional hollow-core fibers, photonic crystal fibers, polymer optical fibers, side-emitting and side-firing fibers, middle-infrared fibers, and optical fiber bundles. Representative applications from the recent literature illustrate how various fibers can be utilized in a wide range of biomedical disciplines. In addition to helping researchers refine current experimental setups, the material in this review paper will help conceptualize and develop emerging optical fiber-based diagnostic and analysis tools.

Fast Photoresponse and Long Lifetime UV Photodetectors and Field Emitters Based on ZnO/Ultrananocrystalline Diamond Films

We have designed photodetectors and UV field emitters based on a combination of ZnO nanowires/nanorods (ZNRs) and bilayer diamond films in a metal-semiconductor-metal (MSM) structure. The ZNRs were fabricated on different diamond films and systematic investigations showed an ultra-high photoconductive response from ZNRs prepared on ultrananocrystalline diamond (UNCD) operating at a lower voltage of 2 V. We found that the ZNRs/UNCD photodetector (PD) has improved field emission properties and a reduced turn-on field of 2.9 V μm(-1) with the highest electron field emission (EFE) by simply illuminating the sample with ultraviolet (UV) light. The photoresponse (Iphoto /Idark ) behavior of the ZNRs/UNCD PD exhibits a much higher photoresponse (912) than bare ZNRs (229), ZNRs/nanocrystalline diamond (NCD; 518), and ZNRs/microcrystalline diamond (MCD; 325) under illumination at λ=365 nm. A photodetector with UNCD films offers superior stability and a longer lifetime compared with carbon materials and bare ZNRs. The lifetime stability of the ZNRs/UNCD-based device is about 410 min, which is markedly superior to devices that use bare ZNRs (92 min). The ZNRs/UNCD PD possesses excellent photoresponse properties with improved lifetime and stability; in addition, ZNRs/UNCD-based UV emitters have great potential for applications such as cathodes in flat-panel displays and microplasma display devices.

Electroabsorption Modulated Lasers With High Immunity to Residual Facet Reflection by Using Lasers With Partially Corrugated Gratings

Residual facet reflection can significantly degrade the performance of electroabsorption modulated lasers (EMLs) operating at high data rates. This issue also complicates the fabrication and characterization of the highly demanded light sources for optical interconnects and transmission. It is desired to optimize the device structure to make EMLs robust and immune to residual facet reflection. EMLs with a partially corrugated-grating DFB section are designed and optimized to have much improved tolerance to the residual optical reflection from the modulator output facet. By designing the laser section with an appropriate grating length and linear gain coefficient, the EML can have good tolerance to residual facet reflection. The analysis indicates that 100% yield can be obtained with the optimal design. If the EML needs to operate over a wide ranges of gain coefficient and facet reflection, >70% of yield can still be obtained.

Optical Probes and Biosensors

Optical probes and photonics-based biosensors are important tools in most biophotonics diagnostic, therapeutic, imaging, and health-status monitoring instrumentation setups. These devices can selectively detect or analyze specific biological elements, such as microorganisms, organelles, tissue samples, cells, enzymes, antibodies, and nucleic acids derived from human and animal tissue and body fluids, cell cultures, foods, or air, water, soil, and vegetation samples. Of particular interest for biosensing processes are optical fiber probes, nanoparticle-based sensors, optical fiber and waveguide substance sensors, photodetector arrays, fiber Bragg grating sensors, and surface plasmon resonance devices.

Fundamentals of Light Sources

A broad selection of light sources is available for the biophotonics UV, visible, or infrared regions. These sources include arc lamps, light emitting diodes, laser diodes, superluminescent diodes, and various types of gas, solid-state, and optical fiber lasers. This chapter first defines terminology used in radiometry, which deals with the measurement of optical radiation. Understanding this terminology is important when determining and specifying the degrees of interaction of light with tissue. Next the characteristics of optical sources for biophotonics are described. This includes the spectrum over which the source emits, the emitted power levels as a function of wavelength, the optical power per unit solid angle emitted in a given direction, the light polarization, and the coherence properties of the emission. In addition, depending on the operating principles of the light source, it can emit light in either a continuous mode or a pulsed mode.

A simple design approach of a micro-lens array for fiber optic applications

The implementation of a freeform lens at the end of an optical fiber delivery line is an attractive method to make efficient use of the rapidly expanding light-emitting diode technology for illumination applications. Of particular interest for intelligent homes and extended smart lighting system usage is the design of a freeform lens for creating a uniform illumination pattern with various shapes. For this, first a collimating lens must be created for making the output rays collimated, and then a micro-lens array needs to be built at the lens exit surface by changing the angle of the incident ray in order to meet the light distribution requirements. We present a novel design of a uniform illumination lighting system consisting of a plastic optical fiber and a freeform lens. The resulting illumination pattern has about 91% uniformity on the target plane.

Stimulated Raman Scattering Microscopy for Brain Imaging: Basic Principle, Measurements, and Applications

Stimulated Raman scattering (SRS) microscopy has proven to be a powerful imaging modality over the past decade due to its intrinsic capacity to provide a molecular fingerprint of the target specimen by detecting the vibrational energies associated with its chemical bonds. In fact, SRS automatically avoids the cumbersome process of attaching a fluorophore or fluorescence protein which may alter the intrinsic folding of the molecules due to its larger size and heavier molecular weight. Being a nonlinear imaging technique, SRS also enjoys other advantages such as pinhole-less three-dimensional optical sectioning, non-invasive observation, deep tissue penetration. Additionally, in contrast to coherent anti-Stokes Raman scattering (CARS), which is another coherent Raman technique, SRS signal is identical to spontaneous Raman spectra, linearly dependent on concentration, and free from non-resonant background. In this chapter, the basic principle of SRS microscopy and the corresponding advantages are elucidated. An overview of the advances in SRS measurements is also presented. Specifically, the recent progress in the instrumentation and chemistry related to both label-free and vibrational label-assisted SRS microscopy is reviewed with special emphasis on the brain imaging applications.

Multiscale and Multimodal Imaging for Connectomics

Recent advances in optical imaging tools for mapping the structural and functional connectomes have greatly augmented our understanding of the brains. The brain is a multilayered and multicompartmental organ where the structures possess multiple length scales, ranging from nanometer (single synapses) to centimeter (whole intact organ), and its functions take place at multiple timescales, ranging from sub-milliseconds (synaptic events) to years (behavioral changes). Therefore, neuroscientists need to image neurocircuits not only at nanometric spatial resolution but also in millisecond time frame in large brain volumes to adequately study neuronal functions. An ideal tool for brain imaging should provide high speed, high resolution, and high contrast with deep penetration in large tissue volumes and sufficient molecular specificity. Toward this end, recent progresses in the optical brain imaging technologies have allowed extracting unprecedented insights into brain. In this chapter, we discuss the various imaging modalities aiming for high-throughput brain imaging, as well as the challenges encountered in imaging the connectome.

Basic Principles of Light

The purpose of this chapter is to present an overview of the fundamental behavior of light. Having a good grasp of the basic principles of light is important for understanding how light interacts with biological matter, which is the basis of biophotonics. A challenging aspect of applying light to biological materials is that the optical properties of the materials generally vary with the light wavelength and can depend on factors such as the optical power per area irradiated, the temperature, the light exposure time, and light polarization. The following topics are included in this chapter: the characteristics of lightwaves, polarization, quantization and photon energy, reflection and refraction, and the concepts of interference and coherence.

Fundamentals of Optical Detectors

The photodetection devices used in biophotonics disciplines are semiconductor-based pin and avalanche photodiodes, photomultiplier tubes, and optical detector arrays. The photodetectors can be either single-channel elements or multichannel devices. With a single-channel element only one spectral channel in a biophotonics setup can be monitored at any instance in time. However, multichannel devices can measure multiple spectral channels simultaneously or observe spatial channels individually in different time sequences. Associated with photodetection setups is the need for optical filters, optical couplers, and optical circulators. Optical filters selectively transmit light in one or more specific bands of wavelengths. Optical couplers split or combine two or more light streams, tap off a small portion of optical power for monitoring purposes, or transfer a selective range of optical power. An optical circulator is a non-reciprocal multi-port device that directs light sequentially from port to port in only one direction.