Journal of Trace Elements in Medicine and Biology, May 1, 2022
BACKGROUND Thimerosal (TM) is an organic mercury compound used as a preservative in many pharmaco... more BACKGROUND Thimerosal (TM) is an organic mercury compound used as a preservative in many pharmacological inputs. Mercury toxicity is related to structural and functional changes in macromolecules such as hemoglobin (Hb) in erythrocytes (Ery). METHOD Human Hb and Ery were used to evaluate O2 uptake based on the TM concentration, incubation time, and temperature. The influence of TM on the sulfhydryl content, production of reactive oxygen species (ROS), and membrane fragility was also evaluated. Raman spectra and atomic force microscopy (AFM) profiles for Ery in the presence and absence of TM were calculated, and docking studies were performed. RESULTS At 37 °C, with 2.50 μM TM (higher concentration) and after 5 min of incubation in Hb and Ery, we observed a reduction in O2 uptake of up to 50 %, while HgCl2, which was used as a positive control, showed a reduction of at least 62 %. Total thiol assays in the presence of NEM (thiol blocker) quantified the preservation of almost 60 % of free SH in Ery. Based on the Raman spectrum profile from Ery-TM, structural differences in the porphyrinic ring and the membrane lipid content were confirmed. Finally, studies using AFM showed changes in the morphology and biomechanical properties of Ery. Theoretical studies confirmed these experimental results and showed that the cysteine (Cys) residues present in Hb are involved in the binding of TM. CONCLUSION Our results show that TM binds to human Hb via free Cys residues, causing conformation changes and leading to harmful effects associated with O2 transport.
Detecting changes in the density of biological cells is of paramount importance as it may reveal ... more Detecting changes in the density of biological cells is of paramount importance as it may reveal the cell status in processes such as differentiation and disease. Several methods have been devised to measure cell density in microfluidic devices. Here, we introduce a 3D printed microfluidic wherein cells are levitated by means of the acoustic forces of ultrasonic waves. The density can be inferred by measuring the height versus time of a single cell in free fall. We determine the density of $10\mu$m-polystyrene beads and macrophage cells (line j774.A1) with high accuracy.
Hematological problems are associated with Coronavirus disease 2019 (COVID-19). Respiratory impai... more Hematological problems are associated with Coronavirus disease 2019 (COVID-19). Respiratory impairment is the higher point studied, although without experimental studies related to the oxygen transport performed by erythrocytes. Therefore, we decided to investigate if erythrocytes from COVID-19 patients have their functionality changed. The case-control study included hospitalized patients with a positive real-time polymerase chain reaction (RT-PCR) result admitted to University Hospital. Volunteers (negative RT-PCR results) were recruited as a control group. Thus, we assessed different erythrocytes parameters, oxidative stress markers, and biophysical studies using whole blood and isolated hemoglobin. We found a decrease of 51% in oxygen uptake and reduced antioxidant enzyme activity in COVID-19 patients compared to controls. Raman spectrometry showed structural changes in the hemoglobin and lipids of the erythrocytes from COVID-19 patients; thus, these results were consolidated with an increase in Young's modulus in erythrocytes followed by morphology changes. Besides, isolated hemoglobin from COVID-19 patients has a distinct interaction profile using a ligand model compared to the control. COVID-19 leads to structural, functional, and morphological damage to human erythrocytes. Our data showed structural and molecular changes and induction of oxidative stress in erythrocytes by COVID-19, a new perspective on the contribution of erythrocytes to a respiratory commitment in COVID-19.
Iron oxide/SiO2/NaGdF4:RE (RE = Ce, and Eu; Yb, and Er) NPs upon irradiation of (i) 254 nm UV lig... more Iron oxide/SiO2/NaGdF4:RE (RE = Ce, and Eu; Yb, and Er) NPs upon irradiation of (i) 254 nm UV light shows red lines in (Ce, and Eu) activated systems and (ii) a 980 nm NIR laser shows green lines and mid IR lines in (Yb, and Er) activated systems.
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Abstract Mode-mismatched Thermal Lens (TL) measurements were performed in 70TeO 2–19WO 3–7Na 2 O–... more Abstract Mode-mismatched Thermal Lens (TL) measurements were performed in 70TeO 2–19WO 3–7Na 2 O–4Nb 2 O 5 (% mol) tellurite glasses doped with either Er 3+ or Tm 3+ and co-doped with Er 3+/Tm 3+ ions. Thermo-optical parameters (D, K, ds/dQ and ds/dT) were obtained in function of thulium concentrations (0.39–1.6)× 10 20 ions/cm 3. For Er 3+/Tm 3+ co-doped tellurite glasses, D and K values are practically independent of the Tm 3+ concentrations used in this study. The average values of D and ds/dT obtained for tellurite ...
Abstract The doping of carbon dots (CDs) with non-metallic elements has been a strategy to improv... more Abstract The doping of carbon dots (CDs) with non-metallic elements has been a strategy to improve their optical properties and application fields. In the present work, nitrogen and phosphorus-doped CDs (N, P-CDs) were prepared through one-pot hydrothermal synthesis using phytic acid (PA) and L-arginine (Arg) as precursors. The synthesized N, P-CDs were characterized using transmission electron microscopy, FTIR, Raman, UV-vis, and fluorescence spectroscopies. The N, P-CDs exhibited green fluorescence (λem = 515 nm) that can be quenched sensitively and selectively in the presence of Cr(VI), combining static quenching, electron transfer, and an inner filter effect. Consequently, a new fluorescence sensing method applied to Cr(VI) determination was developed using the presently synthesized fluorescent CDs. Under optimized conditions, a linear range from 0.05 to 3 µM in Cr(VI)) was obtained, with a limit of detection of 26 nM. Additionally, the N, P-CDs were selective toward Cr(VI) in the presence of Cr(III) and twenty other species, indicating its potential use to monitor Cr(VI) in environmental samples. Then, Cr(VI) was successfully determined, with recoveries from 85 to 107 % in water and soil samples. The method, combining high sensitivity and selectivity, is easy to implement and promotes the use and valorization of eco-friendly materials.
In this work we report on the ability of Er/Yb co-doped NaYF 4 nano-crystals and CdTe Quantum Dot... more In this work we report on the ability of Er/Yb co-doped NaYF 4 nano-crystals and CdTe Quantum Dots as two-photon excited fluorescent nano-thermometers. The basic physical phenomena causing the thermal sensitivity of the two-photon excited emission bands have been discussed and the maximum thermal resolution achievable in each case has been estimated. The practical application of both systems for thermal sensing at the micro-scale in biological systems is demonstrated. In particular, they have been used to evaluate the thermal loading induced by tightly focused laser beams in both living cells and fluids.
In this work we evaluate the impact that neodymium ions can have in modern nanomedicine when they... more In this work we evaluate the impact that neodymium ions can have in modern nanomedicine when they are incorporated as optically active dopants in nanocrystals. In particular, we here discuss how the particular absorption and emission properties of this ion can be conveniently exploited for important biomedical applications, such as fluorescence imaging at both in vitro and in vivo level, non-contact nanothermometry and photothermal therapy. All these features can confer neodymium-doped nanoparticles a multifunctional character and so Nd 3þ is also envisaged as a paradigm ion for nanoparticle based theranostic applications.
The current status of the use of core-shell rare-earth-doped nanoparticles for biomedical applica... more The current status of the use of core-shell rare-earth-doped nanoparticles for biomedical applications is reviewed in detail. The different core-shell rareearth-doped nanoparticles developed so far are described and the most relevant examples of their application for imaging, sensing, and therapy are summarized. In addition, the advantages and disadvantages they present are discussed. Finally, a critical opinion of their potential application in real life biomedicine is given.
Nd 3 þ ion doped LaF 3 dielectric nanoparticles have recently emerged as very attractive multifun... more Nd 3 þ ion doped LaF 3 dielectric nanoparticles have recently emerged as very attractive multifunctional nanoparticles capable of simultaneous sub-tissue heating and thermal sensing. Although they have been already used for selective photothermal treatment of cancer tumors in animal models, their real application as self-monitored photothermal agents require further optimization and development. Dynamic adjustment of the therapy parameters is mandatory for non-selective damage minimization. It would require real-time (sub-second) thermal sensing with a sub-degree thermal resolution. In this work we demonstrate that meeting this challenge is, indeed, possible by performing controlled thermal treatment on as-synthesized Nd 3 þ doped LaF 3 nanoparticles. Temperature induced lattice ordering and defect recombination have been concluded to induce, simultaneously, a line fluorescence narrowing, fluorescence brightness enhancement and a remarkable increment in thermal sensitivity. Ex-vivo experiments have demonstrated that, thanks to this multi-parameter optimization, Neodymium doped LaF 3 nanoparticles are capable of real time sub-tissue thermal reading with a temperature resolution as low as 0.7°C.
The continuous development of nanotechnology has resulted in the actual possibility of the design... more The continuous development of nanotechnology has resulted in the actual possibility of the design and synthesis of nanostructured materials with pre-tailored functionabilities. Nanostructures capable of simultaneous heating and local thermal sensing are in strong demand as they would constitute a revolutionary solution to several challenging problems in bio-medicine, including the achievement of real time control during photothermal therapies. Several approaches have been demonstrated to achieve simultaneous heating and thermal sensing at the nanoscale. Some of them lack of sufficient thermal sensitivity and others require complicated synthesis procedures for heterostructure fabrication. In this study, we demonstrate how single core/shell dielectric nanoparticles with a highly Nd(3+) ion doped shell and an Yb(3+),Er(3+) codoped core are capable of simultaneous thermal sensing and heating under an 808 nm single beam excitation. The spatial separation between the heating shell and sensing core provides remarkable values of the heating efficiency and thermal sensitivity, enabling their application in single beam-controlled heating experiments in both aqueous and tissue environments.
The current status of the use of luminescent nanoparticles for thermometry in animal models is re... more The current status of the use of luminescent nanoparticles for thermometry in animal models is reviewed in detail. The different types of luminescent nanoparticles capable of deep tissue temperature sensing are described, paying special attention to the physical mechanisms at the root of their thermal sensing capacity. Their thermal sensitivities are listed and compared. This review describes the most relevant experiments, in which luminescence nanothermometry has been successfully applied at the small animal level, including the development of controlled thermal therapies as well as subtissue diagnosis procedures. Advantages and disadvantages of different luminescent nanothermometers are discussed.
The recent development of core/shell engineering of rare earth doped luminescent nanoparticles ha... more The recent development of core/shell engineering of rare earth doped luminescent nanoparticles has ushered a new era in fluorescence thermal biosensing, allowing for the performance of minimally invasive experiments, not only in living cells but also in more challenging small animal models. Here, the potential use of active-core/active-shell Nd 3+-and Yb 3+-doped nanoparticles as subcutaneous thermal probes has been evaluated. These temperature nanoprobes operate in the infrared transparency window of biological tissues, enabling deep temperature sensing into animal bodies thanks to the temperature dependence of their emission spectra that leads to a ratiometric temperature readout. The ability of active-core/active-shell Nd 3+-and Yb 3+-doped nanoparticles for unveiling fundamental tissue properties in in vivo conditions was demonstrated by subcutaneous thermal relaxation monitoring through the injected core/shell nanoparticles. The reported results evidence the potential of infrared luminescence nanothermometry as a diagnosis tool at the small animal level.
The synthesis of dual-emission nanocomposite materials has emerged as an excellent strategy for d... more The synthesis of dual-emission nanocomposite materials has emerged as an excellent strategy for designing new and advanced luminescent ratiometric thermometers.
Acoustofluidics technology can be used to trap live cells (and also micro/nanoparticles) in micro... more Acoustofluidics technology can be used to trap live cells (and also micro/nanoparticles) in microenvironments suitable for cell assays. Herein, a cheap and easy‐to‐fabricate device is proposed that works with Raman spectroscopy for biosensing applications. The device comprises a 3D‐printed microchamber working as a half‐wavelength acoustic resonator. By tuning the resonance frequency with a low voltage (≈4 V), cells or particles are aggregated and levitated in seconds by the action of the acoustic radiation force. Based on finite element simulations, the radiation force field produced inside the device is described. In the cellular enrichment (aggregation) process, a metastable honeycomb lattice is formed mostly due to the cell‐to‐cell attraction caused by the secondary acoustic radiation force. Orderly and metastable levitating aggregates provide an excellent arrangement for Raman spectroscopy to investigate cells individually. Polystyrene particles are used for the device characterization and Raman acquisition process. Biosensing applications are showcased with live murine macrophages J774.A1, which are used in infection assay of leishmaniasis disease. The unique features of the device, e.g., simple fabrication process with cheap materials, simple operation, fast time response, and formation of metastable cellular aggregates; hold a noteworthy potential for applications in life sciences and biotechnology involving cell assays.
CdTe quantum dots (QD-CdTe) functionalized with mercaptosuccinic acid (MSA) were synthesized in a... more CdTe quantum dots (QD-CdTe) functionalized with mercaptosuccinic acid (MSA) were synthesized in an aqueous medium, varying synthesis time from 0.5 to 4 h. The nanoprobe were characterized by a direct relationship between synthesis time and QD size (2.61-3.04 nm). The QD-CdTe-MSA interacted with protamine (PT), a cationic protein, forming a bioconjugate, thus quenching the photoluminescence intensity and generating an on-off system. The nanoprobe produced at a synthesis time of 1 h (QD-CdTe 1) presented PT's best sensitivity in a succinate buffer (pH = 5). Under the optimized conditions, the proposed method presented a linear range of 0.05-0.5 mg L-1 (10-100 nM), limit of detection (LOD) 0.01 mg L-1 (2 nM), and relative standard deviation (RSD) ≤ 2.01% (n = 10). The interaction of the nanoprobe and PT led to aggregation due to a bioconjugate formation. The systems' hydrodynamic radius varied from 4.31 nm (QD-CdTe 1) to 30.50 nm for the bioconjugate (QD-CdTe 1-PT). The method was sensitive to variation in ionic strength and based on thermodynamic parameters; it was demonstrated that the interaction mechanism occurred preferentially through electrostatic forces. Finally, the method proved to be fast, sensitive, and viable for quantifying PT in drugs and synthetic urine samples with recoveries above 95%.
CdTe quantum dots (CdTe QD) have been produced at different times of synthesis (1, 2, and 4 h) us... more CdTe quantum dots (CdTe QD) have been produced at different times of synthesis (1, 2, and 4 h) using thiols as capping agents: mercaptopropionic acid (MPA), mercaptosuccinic acid (MSA) and N-acetyl-L-cysteine (NAC) using water as a solvent. The produced CdTe QD were characterized by UV-vis and photoluminescence (PL) spectroscopy and showed a relationship among reflux time, size, and spectroscopic properties. CdTe QD were shown to interact with thimerosal (TM), an organic mercury compound, and the PL intensity was effectively quenched, characterizing an ON-OFF process. However, the NAC capped CdTe (CdTe-NAC) at 1 h presented the best sensitivity for TM determination. Under optimized conditions, a linear range from 0.1 to 1.0 μg mL − 1 (0.25-2.5 μM) and a LOD of 26.6 μg L − 1 (66.7 nM) were achieved. The influence of different mercuric species [Hg(II), methylmercury, ethylmercury, and phenylmercury], along with thiosalicylic acid (TSA), and other ionic species on the sensitivity of the method and the interaction mechanism between TM and CdTe-NAC have been discussed. The method was successfully applied for direct quantification of TM in vaccines, and the results were validated by cold vapor atomic fluorescence spectroscopy (CV AFS). Finally, the proposed method proved to be fast, sensitive, and simple for suitable use in vaccine quality control.
Journal of Trace Elements in Medicine and Biology, May 1, 2022
BACKGROUND Thimerosal (TM) is an organic mercury compound used as a preservative in many pharmaco... more BACKGROUND Thimerosal (TM) is an organic mercury compound used as a preservative in many pharmacological inputs. Mercury toxicity is related to structural and functional changes in macromolecules such as hemoglobin (Hb) in erythrocytes (Ery). METHOD Human Hb and Ery were used to evaluate O2 uptake based on the TM concentration, incubation time, and temperature. The influence of TM on the sulfhydryl content, production of reactive oxygen species (ROS), and membrane fragility was also evaluated. Raman spectra and atomic force microscopy (AFM) profiles for Ery in the presence and absence of TM were calculated, and docking studies were performed. RESULTS At 37 °C, with 2.50 μM TM (higher concentration) and after 5 min of incubation in Hb and Ery, we observed a reduction in O2 uptake of up to 50 %, while HgCl2, which was used as a positive control, showed a reduction of at least 62 %. Total thiol assays in the presence of NEM (thiol blocker) quantified the preservation of almost 60 % of free SH in Ery. Based on the Raman spectrum profile from Ery-TM, structural differences in the porphyrinic ring and the membrane lipid content were confirmed. Finally, studies using AFM showed changes in the morphology and biomechanical properties of Ery. Theoretical studies confirmed these experimental results and showed that the cysteine (Cys) residues present in Hb are involved in the binding of TM. CONCLUSION Our results show that TM binds to human Hb via free Cys residues, causing conformation changes and leading to harmful effects associated with O2 transport.
Detecting changes in the density of biological cells is of paramount importance as it may reveal ... more Detecting changes in the density of biological cells is of paramount importance as it may reveal the cell status in processes such as differentiation and disease. Several methods have been devised to measure cell density in microfluidic devices. Here, we introduce a 3D printed microfluidic wherein cells are levitated by means of the acoustic forces of ultrasonic waves. The density can be inferred by measuring the height versus time of a single cell in free fall. We determine the density of $10\mu$m-polystyrene beads and macrophage cells (line j774.A1) with high accuracy.
Hematological problems are associated with Coronavirus disease 2019 (COVID-19). Respiratory impai... more Hematological problems are associated with Coronavirus disease 2019 (COVID-19). Respiratory impairment is the higher point studied, although without experimental studies related to the oxygen transport performed by erythrocytes. Therefore, we decided to investigate if erythrocytes from COVID-19 patients have their functionality changed. The case-control study included hospitalized patients with a positive real-time polymerase chain reaction (RT-PCR) result admitted to University Hospital. Volunteers (negative RT-PCR results) were recruited as a control group. Thus, we assessed different erythrocytes parameters, oxidative stress markers, and biophysical studies using whole blood and isolated hemoglobin. We found a decrease of 51% in oxygen uptake and reduced antioxidant enzyme activity in COVID-19 patients compared to controls. Raman spectrometry showed structural changes in the hemoglobin and lipids of the erythrocytes from COVID-19 patients; thus, these results were consolidated with an increase in Young's modulus in erythrocytes followed by morphology changes. Besides, isolated hemoglobin from COVID-19 patients has a distinct interaction profile using a ligand model compared to the control. COVID-19 leads to structural, functional, and morphological damage to human erythrocytes. Our data showed structural and molecular changes and induction of oxidative stress in erythrocytes by COVID-19, a new perspective on the contribution of erythrocytes to a respiratory commitment in COVID-19.
Iron oxide/SiO2/NaGdF4:RE (RE = Ce, and Eu; Yb, and Er) NPs upon irradiation of (i) 254 nm UV lig... more Iron oxide/SiO2/NaGdF4:RE (RE = Ce, and Eu; Yb, and Er) NPs upon irradiation of (i) 254 nm UV light shows red lines in (Ce, and Eu) activated systems and (ii) a 980 nm NIR laser shows green lines and mid IR lines in (Yb, and Er) activated systems.
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Abstract Mode-mismatched Thermal Lens (TL) measurements were performed in 70TeO 2–19WO 3–7Na 2 O–... more Abstract Mode-mismatched Thermal Lens (TL) measurements were performed in 70TeO 2–19WO 3–7Na 2 O–4Nb 2 O 5 (% mol) tellurite glasses doped with either Er 3+ or Tm 3+ and co-doped with Er 3+/Tm 3+ ions. Thermo-optical parameters (D, K, ds/dQ and ds/dT) were obtained in function of thulium concentrations (0.39–1.6)× 10 20 ions/cm 3. For Er 3+/Tm 3+ co-doped tellurite glasses, D and K values are practically independent of the Tm 3+ concentrations used in this study. The average values of D and ds/dT obtained for tellurite ...
Abstract The doping of carbon dots (CDs) with non-metallic elements has been a strategy to improv... more Abstract The doping of carbon dots (CDs) with non-metallic elements has been a strategy to improve their optical properties and application fields. In the present work, nitrogen and phosphorus-doped CDs (N, P-CDs) were prepared through one-pot hydrothermal synthesis using phytic acid (PA) and L-arginine (Arg) as precursors. The synthesized N, P-CDs were characterized using transmission electron microscopy, FTIR, Raman, UV-vis, and fluorescence spectroscopies. The N, P-CDs exhibited green fluorescence (λem = 515 nm) that can be quenched sensitively and selectively in the presence of Cr(VI), combining static quenching, electron transfer, and an inner filter effect. Consequently, a new fluorescence sensing method applied to Cr(VI) determination was developed using the presently synthesized fluorescent CDs. Under optimized conditions, a linear range from 0.05 to 3 µM in Cr(VI)) was obtained, with a limit of detection of 26 nM. Additionally, the N, P-CDs were selective toward Cr(VI) in the presence of Cr(III) and twenty other species, indicating its potential use to monitor Cr(VI) in environmental samples. Then, Cr(VI) was successfully determined, with recoveries from 85 to 107 % in water and soil samples. The method, combining high sensitivity and selectivity, is easy to implement and promotes the use and valorization of eco-friendly materials.
In this work we report on the ability of Er/Yb co-doped NaYF 4 nano-crystals and CdTe Quantum Dot... more In this work we report on the ability of Er/Yb co-doped NaYF 4 nano-crystals and CdTe Quantum Dots as two-photon excited fluorescent nano-thermometers. The basic physical phenomena causing the thermal sensitivity of the two-photon excited emission bands have been discussed and the maximum thermal resolution achievable in each case has been estimated. The practical application of both systems for thermal sensing at the micro-scale in biological systems is demonstrated. In particular, they have been used to evaluate the thermal loading induced by tightly focused laser beams in both living cells and fluids.
In this work we evaluate the impact that neodymium ions can have in modern nanomedicine when they... more In this work we evaluate the impact that neodymium ions can have in modern nanomedicine when they are incorporated as optically active dopants in nanocrystals. In particular, we here discuss how the particular absorption and emission properties of this ion can be conveniently exploited for important biomedical applications, such as fluorescence imaging at both in vitro and in vivo level, non-contact nanothermometry and photothermal therapy. All these features can confer neodymium-doped nanoparticles a multifunctional character and so Nd 3þ is also envisaged as a paradigm ion for nanoparticle based theranostic applications.
The current status of the use of core-shell rare-earth-doped nanoparticles for biomedical applica... more The current status of the use of core-shell rare-earth-doped nanoparticles for biomedical applications is reviewed in detail. The different core-shell rareearth-doped nanoparticles developed so far are described and the most relevant examples of their application for imaging, sensing, and therapy are summarized. In addition, the advantages and disadvantages they present are discussed. Finally, a critical opinion of their potential application in real life biomedicine is given.
Nd 3 þ ion doped LaF 3 dielectric nanoparticles have recently emerged as very attractive multifun... more Nd 3 þ ion doped LaF 3 dielectric nanoparticles have recently emerged as very attractive multifunctional nanoparticles capable of simultaneous sub-tissue heating and thermal sensing. Although they have been already used for selective photothermal treatment of cancer tumors in animal models, their real application as self-monitored photothermal agents require further optimization and development. Dynamic adjustment of the therapy parameters is mandatory for non-selective damage minimization. It would require real-time (sub-second) thermal sensing with a sub-degree thermal resolution. In this work we demonstrate that meeting this challenge is, indeed, possible by performing controlled thermal treatment on as-synthesized Nd 3 þ doped LaF 3 nanoparticles. Temperature induced lattice ordering and defect recombination have been concluded to induce, simultaneously, a line fluorescence narrowing, fluorescence brightness enhancement and a remarkable increment in thermal sensitivity. Ex-vivo experiments have demonstrated that, thanks to this multi-parameter optimization, Neodymium doped LaF 3 nanoparticles are capable of real time sub-tissue thermal reading with a temperature resolution as low as 0.7°C.
The continuous development of nanotechnology has resulted in the actual possibility of the design... more The continuous development of nanotechnology has resulted in the actual possibility of the design and synthesis of nanostructured materials with pre-tailored functionabilities. Nanostructures capable of simultaneous heating and local thermal sensing are in strong demand as they would constitute a revolutionary solution to several challenging problems in bio-medicine, including the achievement of real time control during photothermal therapies. Several approaches have been demonstrated to achieve simultaneous heating and thermal sensing at the nanoscale. Some of them lack of sufficient thermal sensitivity and others require complicated synthesis procedures for heterostructure fabrication. In this study, we demonstrate how single core/shell dielectric nanoparticles with a highly Nd(3+) ion doped shell and an Yb(3+),Er(3+) codoped core are capable of simultaneous thermal sensing and heating under an 808 nm single beam excitation. The spatial separation between the heating shell and sensing core provides remarkable values of the heating efficiency and thermal sensitivity, enabling their application in single beam-controlled heating experiments in both aqueous and tissue environments.
The current status of the use of luminescent nanoparticles for thermometry in animal models is re... more The current status of the use of luminescent nanoparticles for thermometry in animal models is reviewed in detail. The different types of luminescent nanoparticles capable of deep tissue temperature sensing are described, paying special attention to the physical mechanisms at the root of their thermal sensing capacity. Their thermal sensitivities are listed and compared. This review describes the most relevant experiments, in which luminescence nanothermometry has been successfully applied at the small animal level, including the development of controlled thermal therapies as well as subtissue diagnosis procedures. Advantages and disadvantages of different luminescent nanothermometers are discussed.
The recent development of core/shell engineering of rare earth doped luminescent nanoparticles ha... more The recent development of core/shell engineering of rare earth doped luminescent nanoparticles has ushered a new era in fluorescence thermal biosensing, allowing for the performance of minimally invasive experiments, not only in living cells but also in more challenging small animal models. Here, the potential use of active-core/active-shell Nd 3+-and Yb 3+-doped nanoparticles as subcutaneous thermal probes has been evaluated. These temperature nanoprobes operate in the infrared transparency window of biological tissues, enabling deep temperature sensing into animal bodies thanks to the temperature dependence of their emission spectra that leads to a ratiometric temperature readout. The ability of active-core/active-shell Nd 3+-and Yb 3+-doped nanoparticles for unveiling fundamental tissue properties in in vivo conditions was demonstrated by subcutaneous thermal relaxation monitoring through the injected core/shell nanoparticles. The reported results evidence the potential of infrared luminescence nanothermometry as a diagnosis tool at the small animal level.
The synthesis of dual-emission nanocomposite materials has emerged as an excellent strategy for d... more The synthesis of dual-emission nanocomposite materials has emerged as an excellent strategy for designing new and advanced luminescent ratiometric thermometers.
Acoustofluidics technology can be used to trap live cells (and also micro/nanoparticles) in micro... more Acoustofluidics technology can be used to trap live cells (and also micro/nanoparticles) in microenvironments suitable for cell assays. Herein, a cheap and easy‐to‐fabricate device is proposed that works with Raman spectroscopy for biosensing applications. The device comprises a 3D‐printed microchamber working as a half‐wavelength acoustic resonator. By tuning the resonance frequency with a low voltage (≈4 V), cells or particles are aggregated and levitated in seconds by the action of the acoustic radiation force. Based on finite element simulations, the radiation force field produced inside the device is described. In the cellular enrichment (aggregation) process, a metastable honeycomb lattice is formed mostly due to the cell‐to‐cell attraction caused by the secondary acoustic radiation force. Orderly and metastable levitating aggregates provide an excellent arrangement for Raman spectroscopy to investigate cells individually. Polystyrene particles are used for the device characterization and Raman acquisition process. Biosensing applications are showcased with live murine macrophages J774.A1, which are used in infection assay of leishmaniasis disease. The unique features of the device, e.g., simple fabrication process with cheap materials, simple operation, fast time response, and formation of metastable cellular aggregates; hold a noteworthy potential for applications in life sciences and biotechnology involving cell assays.
CdTe quantum dots (QD-CdTe) functionalized with mercaptosuccinic acid (MSA) were synthesized in a... more CdTe quantum dots (QD-CdTe) functionalized with mercaptosuccinic acid (MSA) were synthesized in an aqueous medium, varying synthesis time from 0.5 to 4 h. The nanoprobe were characterized by a direct relationship between synthesis time and QD size (2.61-3.04 nm). The QD-CdTe-MSA interacted with protamine (PT), a cationic protein, forming a bioconjugate, thus quenching the photoluminescence intensity and generating an on-off system. The nanoprobe produced at a synthesis time of 1 h (QD-CdTe 1) presented PT's best sensitivity in a succinate buffer (pH = 5). Under the optimized conditions, the proposed method presented a linear range of 0.05-0.5 mg L-1 (10-100 nM), limit of detection (LOD) 0.01 mg L-1 (2 nM), and relative standard deviation (RSD) ≤ 2.01% (n = 10). The interaction of the nanoprobe and PT led to aggregation due to a bioconjugate formation. The systems' hydrodynamic radius varied from 4.31 nm (QD-CdTe 1) to 30.50 nm for the bioconjugate (QD-CdTe 1-PT). The method was sensitive to variation in ionic strength and based on thermodynamic parameters; it was demonstrated that the interaction mechanism occurred preferentially through electrostatic forces. Finally, the method proved to be fast, sensitive, and viable for quantifying PT in drugs and synthetic urine samples with recoveries above 95%.
CdTe quantum dots (CdTe QD) have been produced at different times of synthesis (1, 2, and 4 h) us... more CdTe quantum dots (CdTe QD) have been produced at different times of synthesis (1, 2, and 4 h) using thiols as capping agents: mercaptopropionic acid (MPA), mercaptosuccinic acid (MSA) and N-acetyl-L-cysteine (NAC) using water as a solvent. The produced CdTe QD were characterized by UV-vis and photoluminescence (PL) spectroscopy and showed a relationship among reflux time, size, and spectroscopic properties. CdTe QD were shown to interact with thimerosal (TM), an organic mercury compound, and the PL intensity was effectively quenched, characterizing an ON-OFF process. However, the NAC capped CdTe (CdTe-NAC) at 1 h presented the best sensitivity for TM determination. Under optimized conditions, a linear range from 0.1 to 1.0 μg mL − 1 (0.25-2.5 μM) and a LOD of 26.6 μg L − 1 (66.7 nM) were achieved. The influence of different mercuric species [Hg(II), methylmercury, ethylmercury, and phenylmercury], along with thiosalicylic acid (TSA), and other ionic species on the sensitivity of the method and the interaction mechanism between TM and CdTe-NAC have been discussed. The method was successfully applied for direct quantification of TM in vaccines, and the results were validated by cold vapor atomic fluorescence spectroscopy (CV AFS). Finally, the proposed method proved to be fast, sensitive, and simple for suitable use in vaccine quality control.
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