New opportunities for light-based tumor treatment with an “iron fist”

The efficacy of photodynamic treatments of tumors can be significantly improved by using a new generation of nanoparticles that take advantage of the unique properties of the tumor microenvironmen

Avoiding induced heating in optical trap

Paloma Rodríguez-Sevilla, Yuhai Zhang, Patricia Haro-González, Francisco Sanz-Rodríguez, Francisco Jaque, José García Sole, Xiaogang Liu, Daniel Jaque, "Avoiding induced heating in optical trap", Optical Trapping and Optical Micromanipulation XIV, Proc. SPIE 10347 - 1034716 (25 August 2017); doi: 10.1117/12.2276355. ne print or electronic copy may be made for personal use only. Systematic reproduction and distribution, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper are prohibited.Proceedings of XIV Optical Trapping and Optical Micromanipulation Conference (San Diego, California, United States)Luminescence of a single upconverting particle (NaYF 4 :Er 3+ ,Yb 3+ ) can be used to determine the optical trap temperature due to the partial absorption of the trapping beam either by the medium (water) or the optically trapped particle itself. This fact is an important drawback can be reduced by shifting the trapping wavelength out of the water absorption band, or by using time-modulated laser trapping beams. Both approaches have been studied and the results have shown that the thermal loading due to the trapping radiation can be minimized.This work was supported by the Spanish Ministerio de Educación y Ciencia (MAT2016-75362-C3-1-R) and by COST Action 1403. P.H.G. thanks the Spanish Ministerio de Economía y Competitividad (MINECO) for the Juan de la Cierva- Incorporación program. P.R.S. thanks MINECO and the Fondo Social Europeo (FSE) for the “Promoción del talento y su Empleabilidad en I+D+i” statal program (BES-2014-069410

Luminescence based temperature bio-imaging: Status, challenges, and perspectives

The only way to get thermal images of living organisms without perturbing them is to use luminescent probes with temperature-dependent spectral properties. The acquisition of such thermal images becomes essential to distinguish various states of cells, to monitor thermogenesis, to study cellular activity, and to control hyperthermia therapy. Current efforts are focused on the development and optimization of luminescent reporters such as small molecules, proteins, quantum dots, and lanthanide-doped nanoparticles. However, much less attention is devoted to the methods and technologies that are required to image temperature distribution at both in vitro or in vivo levels. Indeed, rare examples can be found in the scientific literature showing technologies and materials capable of providing reliable 2D thermal images of living organisms. In this review article, examples of 2D luminescence thermometry are presented alongside new possibilities and directions that should be followed to achieve the required level of simplicity and reliability that ensure their future implementation at the clinical level. This review will inspire specialists in chemistry, physics, biology, medicine, and engineering to collaborate with materials scientists to jointly develop novel more accurate temperature probes and enable mapping of temperature with simplified technical mean

Luminescence thermometry for brain activity monitoring: A perspective

Minimally invasive monitoring of brain activity is essential not only to gain understanding on the working principles of the brain, but also for the development of new diagnostic tools. In this perspective we describe how brain thermometry could be an alternative to conventional methods (e.g., magnetic resonance or nuclear medicine) for the acquisition of thermal images of the brain with enough spatial and temperature resolution to track brain activity in minimally perturbed animals. We focus on the latest advances in transcranial luminescence thermometry introducing a critical discussion on its advantages and shortcomings. We also anticipate the main challenges that the application of luminescent nanoparticles for brain thermometry will face in next years. With this work we aim to promote the development of near infrared luminescence for brain activity monitoring, which could also benefit other research areas dealing with the brain and its illnessesThis work was financed by the Spanish Ministerio de Innovación y Ciencias under project NANONERV PID 2019-106211RB-I00. BD acknowledges support from the Australian Research Council (DE200100985), RMIT University (Vice-Chancellor’s Fellowship Programme) and the Australian Academy of Sciences (JG Russell Award). PR-S is grateful for a Juan de la Cierva—Incorporación scholarship (IJC2019-041915-I). AB acknowledges funding from Comunidad de Madrid through TALENTO grant ref. 2019-T1/IND-14014. EX is grateful for a Juan de la Cierva - Incorporación scholarship (IJC2020-045229-I

Neural networks push the limits of luminescence lifetime nanosensing

Luminescence lifetime-based sensing is ideally suited to monitor biological systems due to its minimal invasiveness and remote working principle. Yet, its applicability is limited in conditions of low signal-to-noise ratio (SNR) induced by, e.g., short exposure times and presence of opaque tissues. Herein this limitation is overcome by applying a U-shaped convolutional neural network (U-NET) to improve luminescence lifetime estimation under conditions of extremely low SNR. Specifically, the prowess of the U-NET is showcased in the context of luminescence lifetime thermometry, achieving more precise thermal readouts using Ag2S nanothermometers. Compared to traditional analysis methods of decay curve fitting and integration, the U-NET can extract average lifetimes more precisely and consistently regardless of the SNR value. The improvement achieved in the sensing performance using the U-NET is demonstrated with two experiments characterized by extreme measurement conditions: thermal monitoring of free-falling droplets, and monitoring of thermal transients in suspended droplets through an opaque medium. These results broaden the applicability of luminescence lifetime-based sensing in fields including in vivo experimentation and microfluidics, while, hopefully, spurring further research on the implementation of machine learning (ML) in luminescence sensingThis work was financed by the Spanish Ministerio de Innovación y Ciencias under Project Nos. RTI2018-101050-J-I00, NANONERV PID2019-106211RB-I00, NANOGRANZ PID2021-123318OB-I00, TED2021-132317- I00B, and EIN2020-112419. Additional funding was provided by the European Union Horizon 2020 FETOpen project NanoTBTech (Grant No. 801305) and by the Comunidad Autónoma de Madrid (S2022/BMD7403 REMIN-CM). R.M. is grateful to the Spanish Ministerio de Ciencia e Innovación for support to research through a Ramón y Cajal Fellowship (RYC2021-032913-I). L.M. acknowledges a scholarship from the China Scholarship Council (No. 202108350018). I.Z.-G. thanks UCM-Santander for a predoctoral contract (CT63/19-CT64/19). P.R.-S. is grateful for a Juan de la Cierva-Incorporación scholarship (Grant No. IJC2019-041915-I

Bias in Intracellular Luminescence Thermometry: The Case of the Green Fluorescent Protein

Measurement of intracellular temperature in a fast, accurate, reliable, and remote manner is crucial for the understanding of cellular processes. Nanothermometers based on the green fluorescence protein (GFP) are of special interest because intracellular temperature readouts can be obtained from the analysis of the polarization state of its luminescence. Despite the good results provided by GFP thermometers, the reliability of their intracellular thermal readouts is still a question of debate. Here, light is shed on this issue by introducing cell activity as a relevant bias mechanism that prevents the use of GFP for reliable intranuclear thermal measurements. Experimental evidence that this lack of reliability can affect not only GFP but also other widely used thermometers such as semiconductor nanocrystals is provided. It is discussed how differences observed between calibration curves obtained in presence and absence of cell activity can inform about the presence of bias. The presented results and discussion are aimed to warn the community working in intracellular thermometry and encourage authors to approach the issue in a conscious manner. The performance and reliability of the chosen intracellular thermometers must be judiciously assessed. This is the only way intracellular thermometry can progress and deliver indisputable resultsThis work was financed by the Spanish Ministerio de Innovación y Ciencias under Project Nos. RTI2018-101050-J-I00, NANONERV PID2019- 106211RB-I00, and EIN2020-112419. Additional funding was provided by the European Union Horizon 2020 FETOpen project NanoTBTech (Grant No. 801305). P.R.-S. is grateful for a Juan de la Cierva – Incorporación scholarship (Grant No. IJC2019-041915-I). A.E. is grateful to Retos Projects Program of the Spanish Ministry of Science, Innovation, and Universities, the Spanish State Research Agency, co-funded by the European Regional Development Fund (A.E. is an EMBO Young Investigator). S.T. is grateful to AECC (Spanish Association Against Cancer) IDEAS21989THOM

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-

Bismuth selenide nanostructured clusters as optical coherence tomography contrast agents: beyond gold-based particles

Optical coherence tomography (OCT) is an imaging technique currently used in clinical practice to obtain optical biopsies of different biological tissues in a minimally invasive way. Among the contrast agents proposed to increase the efficacy of this imaging method, gold nanoshells (GNSs) are the best performing ones. However, their preparation is generally time-consuming, and they are intrinsically costly to produce. Herein, we propose a more affordable alternative to these contrast agents: Bi2Se3 nanostructured clusters with a desert rose-like morphology prepared via a microwave-assisted method. The structures are prepared in a matter of minutes, feature strong near-infrared extinction properties, and are biocompatible. They also boast a photon-to-heat conversion efficiency of close to 50%, making them good candidates as photothermal therapy agents. In vitro studies evidence the prowess of Bi2Se3 clusters as OCT contrast agents and prove that their performance is comparable to that of GNSsJ.Y. acknowledges the support from the China Scholarship Council (CSC file no. 201704910867). R.M. acknowledges the support of the European Commission through the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie Grant agreement no. 797945 (LANTERNS). This work was supported by the Spanish Ministry of Economy and Competitiveness under projects MAT2017-83111R, MAT2017-85617-R, and PID2019- 106211RB-I00, by the Instituto de Salud Carlos III (PI16/ 00812), by the Comunidad Autonoma de Madrid (B2017/ ́ BMD-3867 RENIM-CM), and cofinanced by the European Structural and Investment Fun

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

Thermoresponsive Polymeric Nanolenses Magnify the Thermal Sensitivity of Single Upconverting Nanoparticles

Lanthanide-based upconverting nanoparticles (UCNPs) are trustworthy workhorses in luminescent nanothermometry. The use of UCNPs-based nanothermometers has enabled the determination of the thermal properties of cell membranes and monitoring of in vivo thermal therapies in real time. However, UCNPs boast low thermal sensitivity and brightness, which, along with the difficulty in controlling individual UCNP remotely, make them less than ideal nanothermometers at the single-particle level. In this work, it is shown how these problems can be elegantly solved using a thermoresponsive polymeric coating. Upon decorating the surface of NaYF4:Er3+,Yb3+ UCNPs with poly(N-isopropylacrylamide) (PNIPAM), a >10-fold enhancement in optical forces is observed, allowing stable trapping and manipulation of a single UCNP in the physiological temperature range (20–45 °C). This optical force improvement is accompanied by a significant enhancement of the thermal sensitivity— a maximum value of 8% °C+1 at 32 °C induced by the collapse of PNIPAM. Numerical simulations reveal that the enhancement in thermal sensitivity mainly stems from the high-refractive-index polymeric coating that behaves as a nanolens of high numerical aperture. The results in this work demonstrate how UCNP nanothermometers can be further improved by an adequate surface decoration and open a new avenue toward highly sensitive single-particle nanothermometryThis work was supported by the Ministerio de Ciencia e Innovación de España (PID2019-106211RB-I00 PID2019-105195RA-I00 and MAT2017- 83111R), by the Comunidad de Madrid (S2017/BMD-3867 RENIM-CM), co-financed by European Structural and Investment Fund and by the Universidad Autónoma de Madrid and Comunidad Autónoma de Madrid (SI1/PJI/2019-00052 and PR38/21-36 ANTICIPA-CM). D.L. acknowledges a scholarship from the China Scholarship Council (201808350097). J.R.B. acknowledges the support from Carl Tryggers Foundation (CTS18:229). M.I.M acknowledges financial support from the Spanish Ministerio de Ciencia e Innovación, through the “María de Maeztu” Programme for Units of Excellence in R&D (CEX2018-000805-M) and the MELODIA PGC2018-095777-B-C22 proje