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Unformatted text preview: -v 1 7.4.5 Micrometer and Nanometer Biosensing Applications \J‘IHr I :n II DIUMEUILAL Ul’l R.) AND LASERS each patient so that not only the path length but alignment remains fixed each time a. reading is taken. In most tissues, including the eye, the change in rotation due to other" chiral molecules such as proteins needs to be accommodated in any final instrument: In addition, most other tissues also have a birefringence associated with them would need to be accounted for in a final polarimetric glucose sensor. The birefringence and retardation of the polarized light and polarized scatte ' ii»- of the tissue is the signal rather than the noise when using polarized light tissue characterization. For example, a scanning laser polarimeter has been .-" to measure changes in retardation of the polarized light impinging on the re ' w“ nerve fiber layer. It has been shown that scanning laser polarimetry provides statistic ally significant higher retardation for normal eyes in certain regions over glauco... eyes. Images generated from the scattering of various forms of polarized light ha .2 also been shown to be able to differentiate between cancer versus normal fibrob V Developments in microtechnology and, in particular, nanotechnology are transfo IT? mg the fields of biosensors, prosthesis and implants, and medical diagnostics. In t -" of medical diagnostics, these devices are being used for external, lab-on-a-chip . I throughput screening for analyzing blood and other samples. Many researchei's companies are developing nanotechnology applications for use inside the body : anticancer drugs, insulin pumps, and gene therapy. Others are working on pros . devices that include nanostructured materials. One nanotechnology that has come to the forefront is that of quantum - ' Quantum dots are devices capable of confining electrons in three dimensions i space small enough that their quantum (wavelike) behavior dominates over,r“' classical (particle-like) behavior. At room temperature, confinement spaces of V 30 nm or smaller are typically required. Once the electrons are confined, they one another and no two electrons can have the same quantum state. Thus, 1- electrons in a quantum dot will form shells and orbitals highly reminiscent of : ones in an atom, and will exhibit many of the optical, electrical, thermal, and ch .. properties of an atom. Quantum dots can be grown chemically as nanoparticles semiconductor surrounded by an insulating layer nearly colloidal in nature. particles can also be deposited onto a substrate, such as a semiconductor patterned with metal electrodes, or they can be crystalized into bulk solids by a V of methods. Either substance can be stimulated with electricity or light (e.g., , order to change its properties. area has been to probe living cells in full color over extended periods of Such a technique could reveal the complex processes that take place in all I organisms in unprecedented detail, such as the development of embryos. ’7 imaging techniques use natural molecules that fluoresce, as discussed such as organic dyes and proteins that are found in jellyfish and fireflies. H 1/.3 I-UNUAMtN IAL) ur FHUIUI I'IIZI‘MflL Il'IEMI'IZU I ix. erncu Ur mac-u each dye emits light over a wide range of wavelengths, which means that their spectra overlap and this makes it difficult to use more than three dyes at a time to tag and image different biological molecules simultaneously. The fluorescence of dyes also tends to fade away quickly over time, whereas semiconductor nanocrystals—quantum dots—can get around these problems. In addition to being brighter and living longer than organic fluorophores, quantum dots have a broader excitation spectrum. This means that a mixture of quantum dots of different sizes can be excited by a light source with a single wavelength, allowing simultaneous detection and imaging in color. Although the preceding example has focused on biomedical sensing using fluores- cent quantum dots, these micro- and nanoparticles can also be made of various materials and used with all of the light propagation methods. For instance, metal nanoparticles such as gold or silver can be used with Raman spectroscopy to produce an effect known as surface-enhanced Raman spectroscopy (SERS) which gives rise to signals a million times more sensitive than regular Raman signals. These same types of metal nano- or microparticles can be injected into cancerous tissue and used as absorbers that when hit with infrared light will absorb the energy, cook the cancerous tumor, and kill it. Since nanoparticle development is still in its infancy, it remains to be seen what other biomedical applications are to come from the combination of these particles with light. 17.5 FUNDAMENTALS OF PHOTOTHERMAL THERAPEUTIC EFFECTS OF LASERS Therapeutic application of a laser is mediated by conversion of photonic energy to absorbed energy within the material phase of the tissue. The primary mode of this energy conversion manifests itself as a nonuniform temperature rise which leads to a series of thermodynamic processes. These thermodynamic processes can then be exploited as a means to affect therapeutic actions such as photothermal coagulation and ablation of tissue. Another mode of interaction is the utilization of the absorbed energy in activation of endogeneous or exogenous photosensitizing agents in a photo— chemical process known as photodynamic therapy. Laser interaction with biological tissue is composed of a combination of optical and thermodynamic processes. An overview of these processes is shown in Figure 17.13. Once laser light is irradiated on tissue, the photons penetrate into the tissue and—depending on the tissue optical properties such as scattering coefficient, absorp— tion coefficient, and refractive index—the energy is distributed within the tissue. A portion of this energy is absorbed by the tissue and is converted into thermal energy, making the laser act as a distributed heat source. This laser-induced heat source in turn initiates a nonequilibrium process of heat transfer manifesting itself by a tem- perature rise in tissue. The combined mechanisms of conduction, convection, and emissive radiation distribute the thermal energy in the tissue, resulting in a time- and space-dependent temperature distribution in the tissue. The temperature distribution ...
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