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Non-linear materials such as upconverting nanoparticles (UCNPs) are emerging technology with fast-growing applications in various fields. The power density dependence of the emission quantum yield (QY) of these non-linear materials makes them challenging to characterize using currently available commercial QY systems. We propose a multimodal system to measure QY over a wide dynamic range (1:104), which takes into account and compensates for various distorting parameters (scattering, beam profile, inner filter effect and bandwidth of emission lines). For this, a beam shaping approach enabling speckle free beam profiles of two different sizes (530 µm or 106 µm) was employed. This provides low noise high-resolution QY curves. In particular, at low power densities, a signal-to-noise ratio of >50 was found. A Tm-based core-shell UCNP with excitation at 976 nm and emission at 804 nm was investigated with the system.

Evaluating the optical properties of biological tissues is needed to achieve accurate dosimetry during photodynamic therapy (PDT). Currently, accurate assessment of the photosensitizer (PS) concentration by fluorescence measurements during PDT is typically hindered by the lack of information about tissue optical properties. In the present work, a hand-held fiber-optic probe instrument monitoring fluorescence and reflectance is used for assessing blood volume, reduced scattering coefficient, and PS concentration facilitating accurate dosimetry for PDT. System validation was carried out on tissue phantoms using nonlinear least squares support machine regression analysis. It showed a high correlation coefficient (>0.99) in the prediction of the PS concentration upon a large variety of phantom optical properties. In vivo measurements were conducted in a PDT chlorine e6 dose escalating trial involving 36 male Swiss mice with Ehrlich solid tumors in which fluences of 5, 15, and 40 J cm−2 were delivered at two fluence rates (100 and 40 mW cm−2). Remarkably, quantitative measurement of fluorophore concentration was achieved in the in vivo experiment. Diffuse reflectance spectroscopy (DRS) system was also used to independently measure the physiological properties of the target tissues for result comparisons. Then, blood volume and scattering coefficient measured by the fiber-optic probe system were compared with the corresponding result measured by DRS and showed agreement. Additionally, tumor hemoglobin oxygen saturation was measured using the DRS system. Overall, the system is capable of assessing the implicit photodynamic dose to predict the PDT outcome.

The intention with this chapter is to briefly review the capabilities made possible in the field of biomedical diagnostics and treatment by employing upconverting nanoparticles (UCNPs), as well as the importance of appropriate light sources for such applications. The field of UCNPs in biomedicine has grown rapidly the last decade, since they first were made sufficiently small and bright to be of real interest for biomedical applications. This research has been reviewed previously, while this chapter will focus on recent advances in the use of UCNPs for preclinical applications and diagnostic assays using laser diode excitation.

The quantum yield is a critically important parameter in the development of lanthanide-based upconverting nanoparticles (UCNPs) for use as novel contrast agents in biological imaging and optical reporters in assays. The present work focuses on the influence of the beam profile in measuring the quantum yield (ϕ) of nonscattering dispersions of nonlinear upconverting probes, by establishing a relation between ϕ and excitation light power density from a rate equation analysis. A resulting 60% correction in the measured ϕ due to the beam profile utilized for excitation underlines the significance of the beam profile in such measurements, and its impact when comparing results from different setups and groups across the world.

We have synthesized and evaluated in tissue phantom measurements a new type of Nd-codoped upconverting nanoparticles. They provide improved signal strengths from deep regions in a tissue phantom as compared to conventional upconverting nanoparticles, a result also suggesting they will provide less issues with heating the tissue during measurements.

Activities for deep tissue imaging and photoactivation will be presented. Wihin Biophotonics@Tyndall projects based on upconverting nanoparticles and ultrasound optical tomography will be pursued. Data from collaborative research will be given.

Optical techniques for tissue diagnostics currently are experiencing tremendous growth in biomedical applications, mainly due to their noninvasive, inexpensive, and real-time functionality. Here, we demonstrate a hand-held fiber optic probe instrument based on fluorescence/reflectance spectroscopy for precise tumor delin- eation. It is mainly aimed for brain tumor resection guidance with clinical adaptation to minimize the disruption of the standard surgical workflow and is meant as a complement to the state-of-the-art fluorescence surgical microscopy technique. Multiple light sources with fast pulse modulation and detection enable precise quantifi- cation of protoporphyrin IX (PpIX), tissue optical properties, and ambient light suppression. Laboratory measure- ments show the system is insensitive to strong ambient light. Validation measurements of tissue phantoms using nonlinear least squares support vector machines (LS-SVM) regression analysis demonstrate an error of

Glioblastoma multiforme (GBM) has long been known as the most common and aggressive form of brain malignancy. The morphological similarities of the malignant and surrounding tissue cause difficulties to distinct the tumors during surgery. In order to achieve better results in resecting malignant brain tumors, a fiber based optical system which can be used intraoperative is developed in this project. In this context, the system hardware details, system controlling interfaces and laboratory testing results are presented. Based on the results obtained from various tests with tissue-equivalent phantoms, the system is proved to have stable performance, robust structure, and have good linearity as well as high sensitivity to low PpIX concentration under strong ambient light conditions. (Less)

Total resection of glioblastoma multiform (GBM), the most common and aggressive malignant brain tumor, is challenging among other things due to difficulty in intraoperative discrimination between normal and residual tumor cells. This project demonstrates the potential of a system based on a combination of autofluorescence and diffuse reflectance spectroscopy to be useful as an intraoperative guiding tool. In this context, a system based on 5 LEDs coupled to optical fibers was employed to deliver UV/visible light to the sample sequentially. Remitted light from the tissue; including diffuse reflected and fluorescence of endogenous and exogenous fluorophores, as well as its photobleaching product, is transmitted to one photodiode and four avalanche photodiodes. This instrument has been evaluated with very promising results by performing various tissue-equivalent phantom laboratory and clinical studies on skin lesions.

Ytterbium (Yb 3+ )-sensitized upconverting nanoparticles (UCNPs) are excited at 975 nm causing relatively high absorption in tissue. A new type of UCNPs with neodymium (Nd 3+ ) and Yb 3+ codoping is excitable at a 808-nm wavelength. At this wavelength, the tissue absorption is lower. Here we quantify, both experimentally and theoretically, to what extent Nd 3+ -doped UCNPs will provide an increased signal at larger depths in tissue compared to conventional 975-nm excited UCNPs.

Deep tissue excitation of upconverting nanoparticles is limited for biomedical applications by water absorption. By modifying the nanoparticles to shift the excitation wavelength, we demonstrate better depth sensitivity.