Fluorescent implants

Evidence concerning the identity of the mobile species can be obtained from observation [406,411—413] of the dispositions of product phases and phase boundaries relative to inert and immobile markers implanted at the plane of original contact between reactant surfaces. Movement of the markers themselves is known as the Kirkendall effect [414], Carter [415] has used pores in the material as markers. Product layer thickness has alternatively been determined by the decrease in intensity of the X-ray fluorescence from a suitable element which occurs in the underlying reactant but not in the intervening product layers [416]. 

Modification of Cells for Transport Experiments Experimental control of intracellular environment, 171, 817 implantation of isolated carriers and receptors into living cells by Sendai virus envelope-mediated fusion, 171, 829 resonance energy transfer microscopy visual colocalization of fluorescent lipid probes in liposomes, 171, 850. 

This chapter provides a synopsis of the salient host tissue responses that relate to implanted sensor performance and describes in detail the development and current adaptation of the window chamber-biosensor method to address host tissue factors. The use of normoglycemic and diabetic animal models, specifically the Syrian hamster and Fat Sand Rat, to study the role of the microvasculature on sensor function is described. Limitations of the window chamber-biosensor method are also outlined. Finally, some important and useful features of standard brightfield, fluorescence, confocal, and multiphoton imaging as they apply to the window chamber are noted. 

Figure 10.1 contains an illustration of an implanted fluorescence-based sensor assuming the implanted materials and monitoring system can be designed to have each of the properties described above, this configuration is ideal, as it does not require any transdermal connections or implanted electronics. 

Tissue also contains some endogenous species that exhibit fluorescence, such as aromatic amino acids present in proteins (phenylalanine, tyrosine, and tryptophan), pyridine nucleotide enzyme cofactors (e.g., oxidized nicotinamide adenine dinucleotide, NADH pyridoxal phosphate flavin adenine dinucleotide, FAD), and cross-links between the collagen and the elastin in extracellular matrix.100 These typically possess excitation maxima in the ultraviolet, short natural lifetimes, and low quantum yields (see Table 10.1 for examples), but their characteristics strongly depend on whether they are bound to proteins. Excitation of these molecules would elicit background emission that would contaminate the emission due to implanted sensors, resulting in baseline offsets or even major spectral shifts in extreme cases therefore, it is necessary to carefully select fluorophores for implants. It is also noteworthy that the lifetimes are fairly short, such that use of longer lifetime emitters in sensors would allow lifetime-resolved measurements to extract sensor emission from overriding tissue fluorescence. 

SMSI (Montgomery County, MD www.s4ms.com/) is developing a fully implantable system that integrates fluorescence glucose-sensing chemistry, light source, detector,... 

McShane MJ, Russell RJ, Pishko MV, Cote GL. Glucose monitoring using implanted fluorescent microspheres. IEEE Engineering in Medicine and Biology Magazine 2000, 19, 36 15. 

McShane MJ, Rastegar S, Pishko M, Cote GL. Monte Carlo modeling for implantable fluorescent analyte sensors. IEEE Transactions on Biomedical Engineering 2000, 47, 624-632. 

The measured signal from an in vivo fluorescence-based sensor depends on both the quantum yield of the fluorophore, which is the ratio of emitted photons to absorbed photons, and the absorption of the excited and emitted light by the surrounding tissue.12-15 While SWNT have a much lower quantum yield than many visible fluorophores, the most important factor for depth of implantation actually turns out to be the absorption coefficient of the surrounding medium.16,17 A one-dimensional absorption-fluorescence model can be used to compare the suitability of fluorophores for in vivo applications ... 

Figure 11.6 Dialysis capillary setup that could be used to employ the SWNT sensing system in vivo. The dextran-SWNT and Con A mixture is retained in the capillary while glucose is free to diffuse across the membrane. A biocompatible hydrogel, filled with VEGF, can be used to coat the capillary. Such a system could be implanted beneath the skin, with SWNT excitation from a laser photodiode and fluorescence detection from a CCD camera. Adapted with permission from Ref. 17.

Apart from Eu3+ and Tb3+, few studies have been reported on optical properties of lanthanide ions doped in ZnS nanociystals. Bol et al. (2002) attempted to incorporate Er3"1" in ZnS nanociystal by ion implantation. They annealed the sample at a temperature up to 800 °C to restore the crystal structure around Er3"1", but no Er3"1" luminescence was observed. Schmidt et al. (1998) employed a new synthesis strategy to incorporate up to 20 at% Er3"1" into ZnS (1.5-2 nm) cluster solutions which were stabilized by (aminopropyl)triethoxysilane (AMEO). Ethanolic AMEO-stabilized Er ZnS clusters in solutions fluoresce 200 times stronger at 1540 nm than that of ethanolic AMEO-Er complexes. This is explained by the very low phonon energies in ZnS QDs, and indicates that Er3+ ions are trapped inside chalcogenide clusters. However the exact position of Er3+ in ZnS clusters remains unknown. Further spectroscopic and structural analyses are required in order to obtain more detailed information. 

Tsuji, H., Sakai, N., Sugahara, H., Gotoh, Y. and Ishikawa, J. (2005). Silver negative-ion implantation to sol-gel Ti02 film for improving photocatalytic property under fluorescent light. Nucl. Instrum. Methods Phys. Res. Sect. B-Beam Interact. Mater. Atoms 237(1-2), 433 137. 

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