-
Projects
PROY_E17_24. Microsampling and high-temporal and -spatial resolution for minimally invasive clinical analysis and single-cell analysis
- Start date: 01-01-2024
- End date: 31-12-2026
- Coordinator: Martín Resano and Eduardo Bolea Fernández
- Type: Development of R&D&I projects in priority fields and multidisciplinary areas for the 2024–2026 period. Government of Aragón
Abstract: The project aims to develop new analytical methodologies that allow, on one hand, the quantitative analysis of dried blood spots and, on the other, single-cell analysis—both using ICP-MS technology and new microsampling strategies. In order to improve these methods and expand their application range, it is necessary to explore both the use of novel devices capable of handling samples in the micro- and nanoliter range, and the development of alternative sample introduction approaches based on microfluidics.
The use of an automated nanoliquid dispenser system may contribute to the development of new analytical methods for determining low concentrations of analytes in all types of micro/nano samples, including cells. These devices are capable of dispensing controlled volumes and ensuring the presence of cells in each droplet with high efficiency, greatly facilitating single-cell analysis. Likewise, these devices allow for the precise deposition of nanovolumes of blood or other fluids onto DBS supports, ensuring a more uniform and controlled distribution of the sample. Using these devices, DBSs can also be functionalized with enzymes, markers, or antibodies, enabling subsequent analysis and opening the door to the detection of species beyond elemental ones.
The use of microfluidic chips as a sample introduction medium can be considered an elegant approach to overcoming the challenge of introducing individual entities. These chips offer the possibility of encapsulating cells before introducing them into the ICP, thereby increasing the likelihood that cells remain intact through the introduction process. Introduction efficiencies are also expected to be much higher compared to other alternative approaches. Finally, functionalizing these devices enables additional operations, including reactions and separations. This opens new avenues for online analysis of various cell types and/or for labeling with specific antibodies, which could enable the study of different cell types, states, and functions in cell suspensions.
PUBLICATIONS
2024
Bazo, Antonio; Bolea-Fernandez, Eduardo; Rua-Ibarz, Ana; Aramendía, Maite; Resano, Martín
En: Analytica Chimica Acta, vol. 1331, pp. 343305, 2024, ISSN: 0003-2670.
@article{BAZO2024343305,
title = {Intensity- and time-based strategies for micro/nano-sizing via single-particle ICP-mass spectrometry: A comparative assessment using Au and SiO2 as model particles},
author = {Antonio Bazo and Eduardo Bolea-Fernandez and Ana Rua-Ibarz and Maite Aramendía and Martín Resano},
url = {https://www.sciencedirect.com/science/article/pii/S0003267024011061},
doi = {https://doi.org/10.1016/j.aca.2024.343305},
issn = {0003-2670},
year = {2024},
date = {2024-01-01},
urldate = {2024-01-01},
journal = {Analytica Chimica Acta},
volume = {1331},
pages = {343305},
abstract = {Background
Single-particle ICP-mass spectrometry (SP-ICP-MS) is a powerful method for micro/nano-particle (MNP) sizing. Despite the outstanding evolution of the technique in the last decade, most studies still rely on traditional approaches based on (1) the use of integrated intensity as the analytical signal and (2) the calculation of the transport efficiency (TE). However, the increasing availability of MNP standards and advancements in hardware and software have unveiled new venues for MNP sizing, including TE-independent and time-based approaches. This work systematically examines these different methodologies to identify and summarize their strengths and weaknesses, thus helping to determine their preferred application areas.
Results
Different SP-ICP-MS methods for MNP sizing were assessed using AuNPs (20–70 nm) and SiO2MNPs (100–1000 nm). Among TE-dependent approaches, the particle frequency method was characterized by larger uncertainties than the particle size method. The results of the latter were dependent on the appropriate selection of the reference MNP, making the use of multiple reference MNPs recommended. TE-independent methods were based on external (linear and polynomial) calibrations and a relative approach. These methods exhibited the lowest uncertainties of all the strategies evaluated. External calibrations benefited from simpler calculations, but their application could be hindered by a lack of reference MNPs within the desired size range or by the need for interpolations outside the calibration range. Finally, transit time signals are directly proportional to the MNP size rather than its mass. The time-based method demonstrated adequate performance for sizing AuNPs but failed when sizing the largest SiO2MNPs (1000 nm).
Significance and novelty
This work provides further insights into the application of different SP-ICP-MS methodologies for MNP sizing. Both TE-independent approaches and the monitoring of the transit time as the analytical signal are underused strategies; in this context, a Python script was developed for accurate transit time measurement. After 20 years of development, a quantitative comparison of the different methodologies, including the most novel approaches, is deemed necessary for further growth on solid theoretical ground.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Single-particle ICP-mass spectrometry (SP-ICP-MS) is a powerful method for micro/nano-particle (MNP) sizing. Despite the outstanding evolution of the technique in the last decade, most studies still rely on traditional approaches based on (1) the use of integrated intensity as the analytical signal and (2) the calculation of the transport efficiency (TE). However, the increasing availability of MNP standards and advancements in hardware and software have unveiled new venues for MNP sizing, including TE-independent and time-based approaches. This work systematically examines these different methodologies to identify and summarize their strengths and weaknesses, thus helping to determine their preferred application areas.
Results
Different SP-ICP-MS methods for MNP sizing were assessed using AuNPs (20–70 nm) and SiO2MNPs (100–1000 nm). Among TE-dependent approaches, the particle frequency method was characterized by larger uncertainties than the particle size method. The results of the latter were dependent on the appropriate selection of the reference MNP, making the use of multiple reference MNPs recommended. TE-independent methods were based on external (linear and polynomial) calibrations and a relative approach. These methods exhibited the lowest uncertainties of all the strategies evaluated. External calibrations benefited from simpler calculations, but their application could be hindered by a lack of reference MNPs within the desired size range or by the need for interpolations outside the calibration range. Finally, transit time signals are directly proportional to the MNP size rather than its mass. The time-based method demonstrated adequate performance for sizing AuNPs but failed when sizing the largest SiO2MNPs (1000 nm).
Significance and novelty
This work provides further insights into the application of different SP-ICP-MS methodologies for MNP sizing. Both TE-independent approaches and the monitoring of the transit time as the analytical signal are underused strategies; in this context, a Python script was developed for accurate transit time measurement. After 20 years of development, a quantitative comparison of the different methodologies, including the most novel approaches, is deemed necessary for further growth on solid theoretical ground.