In Vivo Spectral Distortions of Infrared Luminescent Nanothermometers Compromise Their Reliability

“This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Nano, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see: https://pubs.acs.org/doi/full/10.1021/acsnano.9b08824Luminescence nanothermometry has emerged over the past decade as an exciting field of research due to its potential applications where conventional methods have demonstrated to be ineffective. Preclinical research has been one of the areas that have benefited the most from the innovations proposed in the field. Nevertheless, certain questions concerning the reliability of the technique under in vivo conditions have been continuously overlooked by most of the scientific community. In this proof-of-concept, hyperspectral in vivo imaging is used to explain how unverified assumptions about the thermal dependence of the optical transmittance of biological tissues in the so-called biological windows can lead to erroneous measurements of temperature. Furthermore, the natural steps that should be taken in the future for a reliable in vivo luminescence nanothermometry are discussed together with a perspective view of the field after the findings here reportedThis work was supported by the Spanish Ministry of Economy and Competitiveness under projects MAT2016-75362-C3-1-R, MAT2017-83111R, and MAT2017-85617-R, by the Instituto de Salud Carlos III (PI16/00812), and by the Comunidad Autónoma de Madrid (B2017/BMD-3867RENIMCM) and cofinanced by the European Structural and investment fund. Additional funding was provided by the European Union’s Horizon 2020 FET Open programme (grant agreement No 801305), the Fundación para la Investigación Biomédica del Hospital Universitario Ramón y Cajal project IMP18_38 (2018/0265), and also COST action CA17140. Y. Shen acknowledges a scholarship from the China Scholarship Council (No. 201806870023

Quantification of the resonant energy transfer processes in Er3+/Yb3+ co-doped Ca3Al2Si3O12 glasses

The resonant cross relaxation processes between Yb3+ and Er3+ ions in calcium alumino-silicate glasses have been quantified under selective Er3+ excitation. The infrared emission spectra, measured under steady state conditions (CW excitation to the 4I9/2 erbium level), have allowed to obtain an experimental relationship linking the transfer (Yb3+ → Er3+) and back transfer (Er3+ → Yb3+) parameters. These measurements combined with the dynamics of the main emitting levels, measured under pulsed excitation to the 2H11/2 erbium level, have allowed the fully quantification of the energy transfer parameters. The obtained values, C25=5.5×10−18cm3s−1 (Yb3+ → Er3+), C52=1.5×10−18cm3s−1 (Er3+ → Yb3+) and C27=7.6×10−18cm3s−1 (up-conversion mechanism, estimated from the Judd-Ofelt analysis previously reported), can be used to predict the temporal evolution of the main luminescent emission band

The role of tissue fluorescence in in vivo optical bioimaging

The following article appeared in Journal of Applied Physics 128.17 (2020): 171101 and may be found at https://doi.org/10.1063/5.0021854The technological advancements made in optics and semiconductors (e.g., cameras and laser diodes) working with infrared have brought interest in optical bioimaging back to the forefront of research investigating in vivo medical imaging techniques. The definition of the near-infrared transparency windows has turned optical imaging into more than just a method for topical imaging applications. Moreover, this has focused attention back to tissue fluorescence, emissions by tissues and organs that occur when excited by external illumination sources. Most endogenous fluorophores emit in the blue to green range of the electromagnetic spectrum and the resulting tissue fluorescence can be employed in studies from cells to tissue metabolism or avoided by shifting to the red if seen as unwanted autofluorescence. With the more recent move to infrared, it was discovered that autofluorescence is not limited to the visible but also strongly affects in vivo imaging in the infrared. In this Tutorial, we give an overview on tissue fluorescence and tissue interactions with excitation light as well as their effect on in vivo imaging. Furthermore, potential sources of tissue fluorescence in the near-infrared are identified and we describe approaches for successful biomedical imaging in the biological windows, taking into consideration infrared autofluorescence and summarizing techniques for avoiding it in in vivo imaging experimentsThis work was supported by the Spanish Ministry of Economy and Competitiveness under Project No. MAT2016-75362-C3-1-R, the Spanish Ministry of Sciences, Innovation and Universities under Project No. PID2019-106211RB-I00 (NANONERV), by the Instituto de Salud Carlos III (Nos. PI16/00812 and PI19/00565), and through the Comunidad Autónoma de Madrid (No. B2017/ BMD-3867RENIMCM), and co-financed by the European Structural and investment fund. Additional funding was provided by the European Union’s Horizon 2020 FET Open project NanoTBTech (Grant Agreement No. 801305), the Fundación para la Investigación Biomédica del Hospital Universitario Ramón y Cajal under Project No. IMP18_38(2018/0265), and also COST action CA17140. Y.S. acknowledges a scholarship from the China Scholarship Council (No.201806870023), E.X. is grateful for a Juan de la Cierva Formación scholarship (No. FJC2018-036734-I), and D.H.O. is thankful to the Instituto de Salud Carlos III for a Sara Borrell Fellowship (No. CD17/00210). The authors thank Dr. Blanca del Rosal for the helpful discussion and input on the manuscrip

3D Optical Coherence Thermometry Using Polymeric Nanogels

In nanothermometry, the use of nanoparticles as thermal probes enables remote and minimally invasive sensing. In the biomedical context, nanothermometry has emerged as a powerful tool where traditional approaches, like infrared thermal sensing and contact thermometers, fall short. Despite the strides of this technology in preclinical settings, nanothermometry is not mature enough to be translated to the bedside. This is due to two major hurdles: the inability to perform 3D thermal imaging and the requirement for tools that are readily available in the clinics. This work simultaneously overcomes both limitations by proposing the technology of optical coherence thermometry (OCTh). This is achieved by combining thermoresponsive polymeric nanogels and optical coherence tomography (OCT)—a 3D imaging technology routinely used in clinical practice. The volume phase transition of the thermoresponsive nanogels causes marked changes in their refractive index, making them temperature-sensitive OCT contrast agents. The ability of OCTh to provide 3D thermal images is demonstrated in tissue phantoms subjected to photothermal processes, and its reliability is corroborated by comparing experimental results with numerical simulations. The results included in this work set credible foundations for the implementation of nanothermometry in the form of OCTh in clinical practiceThis work was financed by the Spanish Ministerio de Innovación y Ciencia under project NANONERV PID2019-106211RB-I00, NANOGRANZ PID2021-123318OB-I00, PID2020-118878RB-I00, RYC2021-032913-I, and TED2021-132317-I00B and under project COLUMNAS (PID2019- 110632RB-I00), by the Instituto de Salud Carlos III (PI19/00565), by the Comunidad Autónoma de Madrid (S2022/BMD-7403 RENIM-CM and SI3/PJI/2021-00211) and co-financed by the European structural and investment fund. Additional funding was provided by COST action CA17140, supported by COST (European Cooperation in Science and Technology) and the Fundación para la Investigación Biomédica del Hospital Universitario Ramón y Cajal (IMP21_A4 (2021/0427)

The near-infrared autofluorescence fingerprint of the brain

This is the peer reviewed version of the following article: Lifante, J, del Rosal, B, Chaves-Coira, I, Fernández, N, Jaque, D, Ximendes, E. The near-infrared autofluorescence fingerprint of the brain. J. Biophotonics. 2020; 13:e202000154, which has been published in final form at https://doi.org/10.1002/jbio.202000154. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived VersionsThe brain is a vital organ involved in mostof the central nervous system disorders.Their diagnosis and treatment require fast,cost-effective, high-resolution and high-sensitivity imaging. The combinationof a new generation of luminescent nanoparticles and imaging systems work-ing in the second biological window (near-infrared II [NIR-II]) is emerging asa reliable alternative. For NIR-II imaging to become a robust technique at thepreclinical level, full knowledge of the NIR-II brain autofluorescence, responsi-ble for the loss of image resolution and contrast, is required. This work demon-strates that the brain shows a peculiar infrared autofluorescence spectrumthat can be correlated with specific molecular components. The existence ofparticular structures within the brain with well-defined NIR autofluorescencefingerprints is also evidenced, opening the door to in vivo anatomical imaging.Finally, we propose a rational selection of NIR luminescent probes suitable forlow-noise brain imaging based on their spectral overlap with brainautofluorescenceComunidad de Madrid, Grant/AwardNumber: B2017/BMD-3867RENIMCM;European Cooperation in Science andTechnology, Grant/Award Number:CA17140; Fundación para la Investigación Biomédica del Hospital Universitario Ramón y Cajal, Grant/Award Number:IMP18_38(2018/0265); Horizon 2020 Framework Programme, Grant/AwardNumber: 801305; Instituto de Salud CarlosIII, Grant/Award Number: PI16/00812;Ministerio de Ciencia, Innovación y Universidades, Grant/Award Number:FJC2018-036734-I; Ministerio deEconomía y Competitividad, Grant/AwardNumbers: MAT2016-75362-C3-1-R,MAT2017-83111R, MAT2017-85617-

Selective Isolation and Identification of Microorganisms with Dual Capabilities: Leather Biodegradation and Heavy Metal Resistance for Industrial Applications

Tanning, crucial for leather production, relies heavily on chromium yet poses risks due to chromium’s oxidative conversion, leading to significant wastewater and solid waste generation. Physico-chemical methods are typically used for heavy metal removal, but they have drawbacks, prompting interest in eco-friendly biological remediation techniques like biosorption, bioaccumulation, and biotransformation. The EU Directive (2018/850) mandates alternatives to landfilling or incineration for industrial textile waste management, highlighting the importance of environmentally conscious practices for leather products’ end-of-life management, with composting being the most researched and viable option. This study aimed to isolate microorganisms from tannery wastewater and identify those responsible for different types of tanned leather biodegradation. Bacterial shifts during leather biodegradation were observed using a leather biodegradation assay (ISO 20136) with tannery and municipal wastewater as the inoculum. Over 10,000 bacterial species were identified in all analysed samples, with 7 bacterial strains isolated from tannery wastewaters. Identification of bacterial genera like Acinetobacter, Brevundimonas, and Mycolicibacterium provides insights into potential microbial candidates for enhancing leather biodegradability, wastewater treatment, and heavy metal bioremediation in industrial applications.This research was co-financed by the European Union through the European Regional Development Fund, within the Operational Programme of the Valencian Community 2014–2020 within the BIOREQ project with grant number IMDEEA/2021/11; Project UAIND21-02B from University of Alicante

In vivo grading of lipids in fatty liver by near-infrared autofluorescence and reflectance

The prevalence of nonalcoholic fatty liver (NAFLD) is rapidly increasing worldwide. When untreated, it may lead to complications such as liver cirrhosis or hepatocarcinoma. The diagnosis of NAFLD is usually obtained by ultrasonography, a technique that can underestimate its prevalence. For this reason, physicians aspire for an accurate, cost-effective, and noninvasive method to determine both the presence and the specific stage of the NAFLD. In this paper, we report an integrated approach for the quantitative estimation of the density of triglycerides in the liver based on the use of autofluorescence and reflectance signals generated by the abdomen of obese C57BL6/J mice. Singular value decomposition is applied to the generated spectra and its corresponding regression model provided a determination coefficient of 0.99 and a root mean square error of 240 mg/dl. This, in turn, enabled the quantitative imaging of triglycerides density in the livers of mice under in vivo conditionsMinisterio de Ciencia e Innovacion, Grant/Award Number: IJC2020-045229-I; Ministerio de Ciencia e Innovacion, Grant/Award Number: NANONERVPID2019-106211RB-I0

Educación en aulas hospitalarias: Aprendizaje a través de proyectos

Las aulas hospitalarias son unidades escolares específicas dentro de los hospitales. Tienen como objetivo principal atender las actividades académicodocentes de los alumnos hospitalizados. Al mismo tiempo, ayudan a prevenir y evitar el posible desfase formativo que puede sufrir el estudiante a causa de una estancia prolongada en el hospital. Estas aulas hospitalarias están ubicadas en el mismo hospital por su circunstancia. Además, aunque se disponga de las instalaciones y recursos oportunos, no siempre se puede impartir la materia de Tecnología. Por este motivo, el alumnado de secundaria que padece enfermedades de larga duración queda, en ocasiones, exento de realizar los trabajos del curso mencionado. El presente trabajo plantea el aprendizaje de Tecnología en aulas hospitalarias a través de la realización de proyectos. Para ello, se han desarrollado experiencias piloto con alumnos del Máster de Secundaria de la Universidad de Valencia y con niños enfermos de cáncer en las instalaciones de la Asociación de Padres de Niños Enfermos de Cáncer de Valencia (ASPANION)

Early in vivo detection of denervation-induced atrophy by luminescence transient nanothermometry

Denervation induces skeletal muscle atrophy due to the loss of control and feedback with the nervous system. Unfortunately, muscle atrophy only becomes evident days after the denervation event when it could be irreversible. Alternative diagnosis tools for early detection of denervation-induced muscle atrophy are, thus, required. In this work, we demonstrate how the combination of transient thermometry, a technique already used for early diagnosis of tumors, and infrared-emitting nanothermometers makes possible the in vivo detection of the onset of muscle atrophy at short (<1 day) times after a denervation event. The physiological reasons behind these experimental results have been explored by performing three dimensional numerical simulations based on the Pennes' bioheat equation. It is concluded that the alterations in muscle thermal dynamics at the onset of muscle atrophy are consequence of the skin perfusion increment caused by the alteration of peripheral nervous autonomous system. This work demonstrates the potential of infrared luminescence thermometry for early detection of diseases of the nervous system opening the venue toward the development of new diagnosis toolsComunidad de Madrid, Grant/Award Number: S2017/BMD-3867 RENIM-CM; COST action CA17140 (Nano2Clinic); European Structural and Investment Fund and the Ministerio de Economía y Competitividad-MINECO, Grant/Award Number: PID2019-106211RB-I00; Juan de la Cierva scholarship, Grant/Award Number: IJC2020-045229-

Ultrafast direct laser writing of cladding waveguides in the 0.8CaSiO3-0.2Ca3(PO4)2 eutectic glass doped with Nd3+ ions

We report on tubular cladding optical waveguides fabricated in Neodymium doped Wollastonite-Tricalcium Phosphate glass in the eutectic composition. The glass samples were prepared by melting the eutectic powder mixture in a Pt-Rh crucible at 1600 °C and pouring it in a preheated brass mould. Afterwards, the glass was annealed to relieve the inner stresses. Cladding waveguides were fabricated by focusing beneath the sample surface using a pulsed Ti:sapphire laser with a pulsewidth of 120 fs working at 1 kHz. The optical properties of these waveguides have been assessed in terms of near-field intensity distribution and transmitted power, and these results have been compared to previously reported waveguides with double-line configuration. Optical properties have also been studied as function of the temperature. Heat treatments up to 700 °C were carried out to diminish colour centre losses where waveguide's modes and transmitted power were compared in order to establish the annealing temperature at which the optimal optical properties were reached. Laser experiments are in progress to evaluate the ability of the waveguides for 1064 nm laser light generation under 800 nm optical pumpingThis work has been partially supported by the projects MAT2013-48426-C2-1-R, DISFOTINT (MECC, TEC2010-21574-C02-01/02) and MICROSERES (Comunidad de Madrid, P2009/TIC-1476). Dr. Daniel Sola thanks the Bosch and Siemens Home Appliances Group, the 7th Framework Programme EU No 314630-UV Marking and MAT2013-41045-R for the financial support of his contrac