Optical manipulation of lanthanide-doped nanoparticles: how to overcome their limitations

Since Ashkin's pioneering work, optical tweezers have become an essential tool to immobilize and manipulate microscale and nanoscale objects. The use of optical tweezers is key for a variety of applications, including single-molecule spectroscopy, colloidal dynamics, tailored particle assembly, protein isolation, high-resolution surface studies, controlled investigation of biological processes, and surface-enhanced spectroscopy. In recent years, optical trapping of individual sub-100-nm objects has got the attention of the scientific community. In particular, the three-dimensional manipulation of single lanthanide-doped luminescent nanoparticles is of great interest due to the sensitivity of their luminescent properties to environmental conditions. Nevertheless, it is really challenging to trap and manipulate single lanthanide-doped nanoparticles due to the weak optical forces achieved with conventional optical trapping strategies. This limitation is caused, firstly, by the diffraction limit in the focusing of the trapping light and, secondly, by the Brownian motion of the trapped object. In this work, we summarize recent experimental approaches to increase the optical forces in the manipulation of lanthanide-doped nanoparticles, focusing our attention on their surface modification and providing a critical review of the state of the art and future prospectsThis work was supported by the Ministerio de Ciencia e Innovación de España (PID2019-105195RA-I00) and by Universidad Autónoma de Madrid,Comunidad Autónoma de Madrid(SI1/PJI/2019-00052)

Effect of the Photoexcitation Wavelength and Polarization on the Generated Heat by a Nd-Doped Microspinner at the Microscale

Thermal control at small scales is critical for studying temperature-dependent biological systems and microfluidic processes. Concerning this, optical trapping provides a contactless method to remotely study microsized heating sources. This work introduces a birefringent luminescent microparticle of NaLuF4:Nd3+ as a local heater in a liquid system. When optically trapped with a circularly polarized laser beam, the microparticle rotates and heating is induced through multiphonon relaxation of the Nd3+ ions. The temperature increment in the surrounding medium is investigated, reaching a maximum heating of ≈5 °C within a 30 μm radius around the static particle under 51 mW laser excitation at 790 nm. Surprisingly, this study reveals that the particle’s rotation minimally affects the temperature distribution, contrary to the intuitive expectation of liquid stirring. The influence of the microparticle rotation on the reduction of heating transfer is analyzed. Numerical simulations confirm that the thermal distribution remains consistent regardless of spinning. Instead, the orientation-dependence of the luminescence process emerges as a key factor responsible for the reduction in heating. The anisotropy in particle absorption and the lag between the orientation of the particle and the laser polarization angle contribute to this effect. Therefore, caution must be exercised when employing spinning polarization-dependent luminescent particles for microscale thermal analysis using rotation dynamics.Projects CNS2022-135495, PID2023-151078OB-I00 and TED2021-129937B-I00 funded by MCIN/AEI/10.13039/501100011033 and by the “European Union NextGenerationEU/PRTR”Spanish Ministerio de Universidades, through the FPU program (FPU19/04803)Consejería de Universidad, Investigación e Innovación de la Junta de Andalucía and by FEDER “Una manera de hacer Europa” (P18-FR-3583

Single-Cell Biodetection by Upconverting Microspinners

This is the peer reviewed version of the following article: Ortiz‐Rivero, E., Prorok, K., Skowickł, M., Lu, D., Bednarkiewicz, A., Jaque, D., & Haro‐González, P. (2019). Single‐Cell Biodetection by Upconverting Microspinners. Small, 15(46), 1904154, which has been published in final form at https://doi.org/10.1002/smll.201904154. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived VersionsNear-infrared-light-mediated optical tweezing of individual upconverting particles has enabled all-optical single-cell studies, such as intracellular thermal sensing and minimally invasive cytoplasm investigations. Furthermore, the intrinsic optical birefringence of upconverting particles renders them light-driven luminescent spinners with a yet unexplored potential in biomedicine. In this work, the use of upconverting spinners is showcased for the accurate and specific detection of single-cell and single-bacteria attachment events, through real-time monitoring of the spinners rotation velocity of the spinner. The physical mechanisms linking single-attachment to the angular deceleration of upconverting spinners are discussed in detail. Concomitantly, the upconversion emission generated by the spinner is harnessed for simultaneous thermal sensing and thermal control during the attachment event. Results here included demonstrate the potential of upconverting particles for the development of fast, high-sensitivity, and cost-effective systems for single-cell biodetectionThis work was partially supported by the Ministerio de Economía y Competitividad de España (MAT2016‐75362‐C3‐1‐R) and by the Instituto de Salud Carlos III (PI16/00812), by the Comunidad Autónoma de Madrid (B2017/BMD‐3867RENIMCM), and cofinanced by the European Structural and investment fund Additional funding was provided by COST action CM1403. D.L. thanks the Chinese Scholarship Council for financial support. K.P. acknowledges the support from Foundation for Polish Science (FNP) under START program. A.B. acknowledges financial support from NCN OPUS DEC‐2017/27/B/ST7/01255 gran

MAP17 (PDZK1IP1) and pH2AX are potential predictive biomarkers for rectal cancer treatment efficacy

Rectal cancer represents approximately 10% of cancers worldwide. Preoperative chemoradiotherapy increases complete pathologic response and local control, although it offers a poor advantage in survivorship and sphincter saving compared with that of radiotherapy alone. After preoperative chemoradiotherapy, approximately 20% of patients with rectal cancer achieve a pathologic complete response to the removed surgical specimen; this response may be related to a better prognosis and an improvement in disease-free survival. However, better biomarkers to predict response and new targets are needed to stratify patients and obtain better response rates. MAP17 (PDZK1IP1) is a small, 17 kDa non-glycosylated membrane protein located in the plasma membrane and Golgi apparatus and is overexpressed in a wide variety of human carcinomas. MAP17 has been proposed as a predictive biomarker for reactive oxygen species, ROS, inducing treatments in cervical tumors or laryngeal carcinoma. Due to the increase in ROS, MAP17 is also associated with the marker of DNA damage, phosphoH2AX (pH2AX). In the present manuscript, we examined the values of MAP17 and pH2AX as surrogate biomarkers of the response in rectal tumors. MAP17 expression after preoperative chemoradiotherapy is able to predict the response to chemoradiotherapy, similar to the increase in pH2AX. Furthermore, we explored whether we can identify molecular targeted therapies that could help improve the response of these tumors to radiotherapy. In this sense, we found that the inhibition of DNA damage with olaparib increased the response to radio- and chemotherapy, specifically in tumors with high levels of pH2AX and MAP17.Spanish Ministry of Economy and Competitivity, Plan Estatal de I+D+I 2013–2016, ISCIII (Fis: PI15/00045) and CIBER de Cáncer (CB16/12/00275)co-funded by FEDER from Regional Development European Funds (European Union), Consejería de Ciencia e Innovación (CTS-1848)Consejería de Salud of the Junta de Andalucía (PI-0096–2014)

Laser refrigeration by an Ytterbium-doped NaYF4 microspinner

Thermal control of liquids with high (micrometric) spatial resolution is required for advanced research such as single molecule/cell studies (where temperature is a key factor) or for the development of advanced microfluidic devices (based on the creation of thermal gradients at the microscale). Local and remote heating of liquids is easily achieved by focusing a laser beam with wavelength adjusted to absorption bands of the liquid medium or of the embedded colloidal absorbers. The opposite effect, that is highly localized cooling, is much more difficult to achieve. It requires the use of a refrigerating micro-/nanoparticle which should overcome the intrinsic liquid heating. Remote monitoring of such localized cooling, typically of a few degrees, is even more challenging. In this work, a solution to both problems is provided. Remote cooling in D2O is achieved via anti-Stokes emission by using an optically driven ytterbium-doped NaYF4 microparticle. Simultaneously, the magnitude of cooling is determined by mechanical thermometry based on the analysis of the spinning dynamics of the same NaYF4 microparticle. The angular deceleration of the NaYF4 particle, caused by the cooling-induced increase of medium viscosity, reveals liquid refrigeration by over −6 K below ambient conditionsThis work was supported by the Ministerio de Ciencia e Innovación de España (PID2019-106211RB-I00 and PID2019-105195RA-I00) and by Universidad Autónoma de Madrid and Comunidad Autónoma de Madrid (SI1/PJI/2019-00052). E.O.R gratefully acknowledges the financial support provided by the Spanish Ministerio de Universidades, through the FPU program (FPU19/04803). K.P. acknowledges financial support from NCN, Poland, grant number 2018/31/D/ST5/0132

Avian haemosporidian infections in rufous-collared sparrows in an Andean dry forest: diversity and factors related to prevalence and parasitaemia

Despite intensive research during the last few decades, understanding of ecological and physiological factors related to haemosporidian infections in birds is still fragmentary. Since more model organisms are needed in order to understand these infections in the wild, we analysed avian haemosporidian infections in the rufous-collared sparrow (Zonotrichia capensis, Emberizidae) in a dry forest of the Ecuadorian Andes. Parasite diversity was screened using molecular and morphological approaches. By molecular diagnosis, we identified three linages that were phylogenetically placed in the context of molecular haemosporidian diversity and associated with a morphospecies. By microscopy, we identified five described morphospecies and one additional undescribed morphospecies. We found that avian haemosporidian prevalence on the study site was 76.3%. Additionally, we used a series of generalized linear models to explore the potential relationship of parasite prevalence and parasitaemia with a set of variables related to physiological and environmental conditions. Although our results revealed associations of haemosporidian infections with precipitation, age and sampling site, the models only explained a small fraction of the variation

Light-to-Heat Conversion of Optically Trapped Hot Brownian Particles

Anisotropic hybrid nanostructures stand out as promising therapeutic agents in photothermal conversion-based treatments. Accordingly, understanding local heat generation mediated by light-to-heat conversion of absorbing multicomponent nanoparticles at the single-particle level has forthwith become a subject of broad and current interest. Nonetheless, evaluating reliable temperature profiles around a single trapped nanoparticle is challenging from all of the experimental, computational, and fundamental viewpoints. Committed to filling this gap, the heat generation of an anisotropic hybrid nanostructure is explored by means of two different experimental approaches from which the local temperature is measured in a direct or indirect way, all in the context of hot Brownian motion theory. The results were compared with analytical results supported by the numerical computation of the wavelength-dependent absorption efficiencies in the discrete dipole approximation for scattering calculations, which has been extended to inhomogeneous nanostructures. Overall, we provide a consistent and comprehensive view of the heat generation in optical traps of highly absorbing particles from the viewpoint of the hot Brownian motion theory.Grants PID2022-136919NA-C33, PID2019-106211RB-I00 (NANONERV), PID2021-127427NB-I00, PID2020-118448RBC21, PID2019-105195RA-I00, funded by the Ministerio de Ciencia e Innovación of Spain MCIN/AEI/10.13039/501100011033Grant CNS2022-135495, and TED2021-129937B-I00, funded by MCIN/AEI/10.13039/501100011033“European Union NextGenerationEU/PRTR” from the Ministerio de Economía, Industria y Competitividad of Spain (grant CTQ2017-86655-R) and from FEDER/Consejería de Transformación Económica, Industria, Conocimiento y Universidades of Andalucía (grants P18-FR-3583 and P20_00727/PAIDI2020)HORIZON-MSCA-2021-PF-01 grant agreement ID: 101065163Spanish Ministerio de Universidades, through the FPU program (FPU19/04803)Consejería de Salud y Familias (Junta de Andalucía) for his senior postdoctoral grant (RH-0040-2021

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity