High-sensitivity Technique Research Articles

Classification of soil contamination by heavy metals (Cr, Ni, Pb, Zn) in wildfire-affected areas using laser-induced breakdown spectroscopy and machine learning.

The assessment of soil contamination by heavy metals is of high importance due to its impact on the environment and human health. Standard high-sensitivity spectroscopic techniques for this task such as atomic absorption spectrometry (AAS) and inductively coupled plasma spectrometry (ICP-OES and ICP-MS) are effective but time-consuming and costly, mainly due to sample preparation and lab consumables, respectively. In the present study, a laser-based spectroscopic approach is proposed, laser-induced breakdown spectroscopy (LIBS), which, combined with machine learning (ML), can provide a tool for rapid assessment of soil contamination by heavy metals. A dataset comprising 523 soil samples, from the areas of Mati, Kineta, Varympompi, and Evia (Greece) after the wildfires of 2018 and 2021, was employed to train and validate various ML models. The analysis focused on Cr, Ni, Zn, and Pb concentrations, utilizing environmental and human health screening values for soil classification. Two classification schemes were employed: the first identified samples "outside the danger zone" of contamination, while the second focused on samples "inside the safe zone". The models achieved over 93% performance for Cr, Ni, and Zn in the first scheme and 97% for Pb in the second. These findings demonstrate that LIBS, coupled with ML, can provide a reliable and efficient solution for preliminary assessment of soil contamination, particularly suited for large-scale operations of environmental monitoring and remediation efforts.

Seeing nanoscale electrocatalytic reactions at individual MoS2 particles under an optical microscope: probing sub-mM oxygen reduction reaction.

MoS2 is a promising electrocatalytic material for replacing noble metals. Nanoelectrochemistry studies, such as using nanoelectrochemical cell confinement, have particularly helped in demonstrating the preferential electrocatalytic activity of MoS2 edges. These findings have been accompanied by considerable research efforts to synthesize edge-abundant nanomaterials. However, to fully apprehend their electrocatalytic performance, at the single particle level, new instrumental developments are also needed. Here, we feature a highly sensitive refractive index based optical microscopy technique, namely interferometric scattering microscopy (iSCAT), for monitoring local electrochemistry at single MoS2 petal-like sub-microparticles. This work focuses on the oxygen reduction reaction (ORR), which operates at low current densities and thus requires high-sensitivity imaging techniques. By employing a precipitation reaction to reveal the ORR activity and utilizing the high spatial resolution and contrast of iSCAT, we achieve the sensitivity required to evaluate the ORR activity at single MoS2 particles.

Nasal secretions trace epithelial type 2 response to allergen-specific immunotherapy.

Allergen-specific immunotherapy (AIT) is a disease-modifying therapy and is effective to reduce the symptoms of grass pollen-allergy. The airway epithelium of these patients releases inflammatory mediators including type-2 cytokines, which are associated with cellular processes involved in the symptomatic response of the affected tissue. Aim of the study was to identify epithelial biomarkers indicating AIT progress. In an exploratory, observational allergy cohort, we longitudinally phenotyped 56 grass pollen-allergic patients undergoing AIT for over three years and 18 controls using nasal secretions at critical time windows during therapy to assess peak-season responses along the course of therapy. Type-2 cytokine protein levels were analyzed using the high-sensitivity multiplex electrochemiluminescence mesoscale technique. The type-2 cytokines CCL26 and POSTN oscillated seasonally, in contrast to TSLP and IL-33. However, only POSTN was reduced over the three-year AIT progression. In addition to POSTN, IL-24 and IL-37 levels were continuously reduced during AIT, while IFN-g and CCL27 were increased. Compared to healthy individuals, AIT did not restore healthy secretion levels but rather induced a novel homeostasis CONCLUSION: Nasal secretions trace the epithelial response during different phases of AIT. We demonstrate that AIT only partially controls the epithelial type 2 cytokine CCL26, which also adapts to seasonal changes, while POSTN and IL-24 are potential indicators of therapy success. Therefore, nasal secretions represent a promising, non-invasive tool for monitoring seasonal progress of AIT.

Graphics card-based real-time processing for dual comb interferometry.

The technique of performing interferometry with two optical frequency combs is used by an increasing number of research groups and even for field deployed commercial applications. Real-time interferogram acquisition, correction, and averaging are, however, still not broadly accessible. This limits the deployment and wider adoption of this high resolution, high sensitivity technique. We herein introduce and describe a freely available correction software performing real-time processing on a graphics processing unit.

Development of Trp-AuNPs-rGO based electrochemical active biosensing interface for dopamine detection

Neurotransmitters are essential for learning, mental alertness, blood flow, and emotions. An imbalance of neurotransmitters in the human system causes neurological disorders. An imbalance of dopamine, a neurotransmitter, can cause severe diseases such as Parkinson's disease, restless legs syndrome, depression, schizophrenia, and attention deficit hyperactivity disorder (ADHD). Dopamine detection is essential but requires high sensitivity, temporal resolution, and favorable electrochemical techniques for the sensing mechanism. The ultrasensitive and selective real-time diagnosis of dopamine depends on the fabrication of a brain-on-a-chip model. Prior to fabrication of this device, it is very essential to develop a novel metal nanomaterial that exhibits biocompatibility and fast detection and is capable of improving the quality of the device. In this respect, we prepared amino acid-reduced gold nanoparticles that were supported by reduced graphene oxide. The prepared composite has been characterized by various techniques for internal and external morphology. The electrochemical behavior was examined on a glassy carbon electrode via various electrochemical techniques by a potentiostat instrument towards the diagnosis of dopamine at a micromolar level in the presence of its interference. Finally, as expected, we found 43.59 μAμM−1cm-2 sensitivity toward DA in the linear range of 1-11 μM. Trp-AuNPS-rGO shows promising results toward the diagnosis of dopamine in the presence of its interference and proves that this nanomaterial will be very promising toward the fabrication of a brain-on chip.

Cardiac Troponins I and T as Biomarkers of Cardiomyocyte Injury—Advantages and Disadvantages of Each

Measurement of cardiac troponin in serum is an essential part of diagnosing myocardial infarction in the emergency department. The guidelines suggest that high-sensitivity techniques should be used for measuring cardiac troponin I (cTnI) or cardiac troponin T (cTnT). The aim of our study was to correlate the values of both troponins, and to ascertain which type of troponin is more in agreement with the diagnosis. The patients were classified into four groups: 43 patients in non-ST-elevation myocardial infarction (NSTEMI), 7 in ST-elevation myocardial infarction (STEMI), 48 in Type 2 myocardial infarction, and 21 in the control group. A significant correlation between cTnI and cTnT was found in the NSTEMI (r = 0.70) and Type 2 (r = 0.75) groups while in the control group there was no association (r = −0.06). The ratios of cTnI and cTnT relative to their cut-off values were lower in Type 2 myocardial infarction compared to NSTEMI. This difference can be attributed to the pathophysiology of these two types of heart conditions. The ratio in the NSTEMI group was higher in female than in male patients (53.3 vs. 24.6 ng/L); the same difference was found for the ratio of cTnT (20.8 vs. 13.1 ng/L). In the same manner, the ratios in the Type 2 group were higher in female than in male patients for cTnI (25.6 vs. 12.7 ng/L) as well as for cTnT (19.0 vs. 6.73 ng/L). These differences could be due to biological differences, but they could also be influenced by other factors contributing to different damage responses.

Whole-cerebrum guanidino and amide CEST mapping at 3 T by a 3D stack-of-spirals gradient echo acquisition.

To develop a 3D, high-sensitivity CEST mapping technique based on the 3D stack-of-spirals (SOS) gradient echo readout, the proposed approach was compared with conventional acquisition techniques and evaluated for its efficacy in concurrently mapping of guanidino (Guan) and amide CEST in human brain at 3 T, leveraging the polynomial Lorentzian line-shape fitting (PLOF) method. Saturation time and recovery delay were optimized to achieve maximum CEST time efficiency. The 3DSOS method was compared with segmented 3D EPI (3DEPI), turbo spin echo, and gradient- and spin-echo techniques. Image quality, temporal SNR (tSNR), and test-retest reliability were assessed. Maps of Guan and amide CEST derived from 3DSOS were demonstrated on a low-grade glioma patient. The optimized recovery delay/saturation time was determined to be 1.4/2 s for Guan and amide CEST. In addition to nearly doubling the slice number, the gradient echo techniques also outperformed spin echo sequences in tSNR: 3DEPI (193.8 ± 6.6), 3DSOS (173.9 ± 5.6), and GRASE (141.0 ± 2.7). 3DSOS, compared with 3DEPI, demonstrated comparable GuanCEST signal in gray matter (GM) (3DSOS: [2.14%-2.59%] vs. 3DEPI: [2.15%-2.61%]), and white matter (WM) (3DSOS: [1.49%-2.11%] vs. 3DEPI: [1.64%-2.09%]). 3DSOS also achieves significantly higher amideCEST in both GM (3DSOS: [2.29%-3.00%] vs. 3DEPI: [2.06%-2.92%]) and WM (3DSOS: [2.23%-2.66%] vs. 3DEPI: [1.95%-2.57%]). 3DSOS outperforms 3DEPI in terms of scan-rescan reliability (correlation coefficient: 3DSOS: 0.58-0.96 vs. 3DEPI: -0.02 to 0.75) and robustness to motion as well. The 3DSOS CEST technique shows promise for whole-cerebrum CEST imaging, offering uniform contrast and robustness against motion artifacts.

Characterization of low molecular weight sulfur species in seaweed from the Antarctic continent.

Antarctic seaweeds are vital components of polar marine ecosystems, playing a crucial role in nutrient cycling and supporting diverse life forms. The sulfur content in these organisms is particularly interesting due to its implication in biogeochemical processes and potential impacts on local and global environmental systems. In this study, we present a comprehensive characterization of seaweed collected in the Antarctic in terms of their total sulfur content and its distribution among different classes of species, including thiols, using various methods and high-sensitivity techniques. The data presented in this paper are unprecedented in the scientific literature. These methods allowed for the determination of total sulfur content and the distribution of sulfur compounds in different fractions, such as water-soluble and proteins, as well as the speciation of sulfur compounds in these fractions, providing valuable insights into the chemical composition of these unique marine organisms. Our results revealed that the total sulfur concentration in Antarctic seaweeds varied widely across different species, ranging from 5.5 to 56gkg-1 dry weight. Furthermore, our investigation into the sulfur speciation revealed the presence of various sulfur compounds, including sulfate, and some thiols, which were quantified in all ten seaweed species evaluated. The concentration of these individual sulfur species also displayed considerable variability among the studied seaweeds. This study provides the first in-depth examination of total sulfur content and sulfur speciation in brown and red Antarctic seaweeds.

DNA Nanospheres Assisted Spatial Confinement Signal Amplification for MicroRNA Imaging in Live Cancer Cells.

DNA assemblies are commonly used in biosensing, particularly for the detection and imaging of microRNAs (miRNAs), which are biomarkers associated with tumor progression. However, the difficulty lies in the exploration of high-sensitivity analytical techniques for miRNA due to its limited presence in living cells. In this study, we introduced a DNA nanosphere (DS) enhanced catalytic hairpin assembly (CHA) system for the detection and imaging of intracellular miR-21. The single-stranded DNA with four palindromic portions and extending sequences at the terminal was annealed for assembling DS, which avoided the complex sequence design and high cost of long DNA strands. Benefiting from the multiple modification sites of DS, functional hairpins H1 (modified with Cy3 and BHQ2) and H2 were grafted onto the surface of DS for assembling DS-H1-H2 using a hybridization reaction. The DS-H1-H2 system utilized spatial confinement and the CHA reaction to amplify fluorescence signals of Cy3. This enabled highly sensitive and rapid detection of miR-21 in the range from 0.05 to 3.5 nM. The system achieved a limit of determination (LOD) of 2.0 pM, which was 56 times lower than that of the control CHA circuit with freedom hairpins. Additionally, the sensitivity was improved by 8 times. Moreover, DS-H1-H2 also showed an excellent imaging capability for endogenous miR-21 in tumor cells. This was due to enhanced cell internalization efficiency, accelerated reaction kinetics, and improved biostability. The imaging strategy was shown to effectively monitor the dynamic content of miR-21 in live cancer cells and differentiate various cells. In general, the simple nanostructure DS not only enhanced the detection and imaging capability of the conventional probe but also could be easily integrated with the reported DNA-free probe, indicating a wide range of potential applications.

Simultaneous Detection of Exosomal microRNAs Isolated from Cancer Cells Using Surface Acoustic Wave Sensor Array with High Sensitivity and Reproducibility.

We present a surface acoustic wave (SAW) sensor array for microRNA (miRNA) detection that utilizes photocatalytic silver staining on titanium dioxide (TiO2) nanoparticles as a signal enhancement technique for high sensitivity with an internal reference sensor for high reproducibility. A sandwich hybridization was performed on working sensors of the SAW sensor array that could simultaneously capture and detect three miRNAs (miRNA-21, miRNA-106b, and miRNA-155) known to be upregulated in cancer. Sensor responses due to signal amplification varied depending on the concentration of synthetic miRNAs. It was confirmed that normalization (a ratio of working sensor response to reference sensor response) screened out background interferences by manipulating data and minimized non-uniformity in the photocatalytic silver staining step by suppressing disturbances to both working sensor signal and reference sensor signal. Finally, we were able to successfully detect target miRNAs in cancer cell-derived exosomal miRNAs with performance comparable to the detection of synthetic miRNAs.

A UPLC-MS/MS method for quantification of β-N-methylamino-L-alanine (BMAA) in Cycas sphaerica roxb. And validating efficacy of a traditional BMAA removal method

The presence of neurotoxin β-N-Methylamino-L-alanine (BMAA) in the seeds of Cycas sphaerica is reported for first time. We developed a UPLC-MS/MS method for BMAA quantification by derivatizing with dansyl chloride. The method successfully differentiated L-BMAA from its structural isomer2,4-diaminobutyric acid (DAB).The extracting mixture 0.1M TCA: ACN 4:1 v/v had a recovery level of >95%. The method is a high throughput sensitive chromatographic technique with 16.42 ng g−1 Limit of Quantification. BMAA was present in the endosperm of C. sphaerica, and was not detected in the leaves and pith. Washing of seeds in running cold water for 48 h reduced BMAA content by 86%. The local communities also treat the seeds under running cold water, but only for 24 h. The results of the study thus validated the traditional BMAA removal process through cold water treatment, but recommend for increase in the treatment period to 48 h or more.

Mapping the phase-separated state in a 2D magnet.

Intrinsic 2D magnets have recently been established as a playground for studies on fundamentals of magnetism, quantum phases, and spintronic applications. The inherent instability at low dimensionality often results in coexistence and/or competition of different magnetic orders. Such instability of magnetic ordering may manifest itself as phase-separated states. In 4f 2D materials, magnetic phase separation is expressed in various experiments; however, the experimental evidence is circumstantial. Here, we employ a high-sensitivity MFM technique to probe the spatial distribution of magnetic states in the paradigmatic 4f 2D ferromagnet EuGe2. Below the ferromagnetic transition temperature, we discover the phase-separated state and follow its evolution with temperature and magnetic field. The characteristic length-scale of magnetic domains amounts to hundreds of nanometers. These observations strongly shape our understanding of the magnetic states in 2D materials at the monolayer limit and contribute to engineering of ultra-compact spintronics.

Long-range UWOC system-based high-sensitivity detection techniques

Long-range UWOC system-based high-sensitivity detection techniques

Breast Imaging Physics in Mammography (Part II).

One of the most frequently detected neoplasms in women in Italy is breast cancer, for which high-sensitivity diagnostic techniques are essential for early diagnosis in order to minimize mortality rates. As addressed in Part I of this work, we have seen how conditions such as high glandular density or limitations related to mammographic sensitivity have driven the optimization of technology and the use of increasingly advanced and specific diagnostic methodologies. While the first part focused on analyzing the use of a mammography machine from a physical and dosimetric perspective, in this paper, we will examine other techniques commonly used in breast imaging: contrast-enhanced mammography, digital breast tomosynthesis, radio imaging, and include some notes on image processing. We will also explore the differences between these various techniques to provide a comprehensive overview of breast lesion detection techniques. We will examine the strengths and weaknesses of different diagnostic modalities and observe how, with the implementation of improvements over time, increasingly effective diagnoses can be achieved.

Comparative study of droplet-digital PCR and absolute Q digital PCR for ctDNA detection in early-stage breast cancer patients

BackgroundAnalysis of circulating tumor DNA (ctDNA) is increasingly used for clinical decision-making in oncology. However, ctDNA could represent ≤ 0.1 % of cell-free DNA in early-stage tumors and its detection requires high-sensitive techniques such as digital PCR (dPCR). MethodsIn 46 samples from patients with early-stage breast cancer, we compared two leading dPCR assays for ctDNA analysis: QX200 droplet digital PCR (ddPCR) system from Bio-Rad which is the gold-standard in the field, and Absolute Q plate-based digital PCR (pdPCR) system from Thermo Fisher Scientific which has not been reported before. We analyzed 5 mL of baseline plasma samples prior to any treatment. ResultsBoth systems displayed a comparable sensitivity with no significant differences observed in mutant allele frequency. In fact, ddPCR and pdPCR possessed a concordance > 90 % in ctDNA positivity. Nevertheless, ddPCR exhibited higher variability and a longer workflow. Finally, we explored the association between ctDNA levels and clinicopathological features. Significantly higher ctDNA levels were present in patients with a Ki67 score > 20 % or with estrogen receptor-negative or triple-negative breast cancer subtypes. ConclusionBoth ddPCR and pdPCR may constitute sensitive and reliable tools for ctDNA analysis with an adequate agreement in early-stage breast cancer patients.

The importance of BMPs and TGF-βs for endochondral bone repair – A longitudinal study in hip arthroplasty patients

IntroductionOsseointegration of hip implants, although a decade-long process, shows striking similarities with the four major phases of endochondral bone repair. In the current study we investigated the spatiotemporal involvement of bone morphogenic proteins (BMPs) and transforming growth factor betas (TGF-βs) throughout the process of bone repair leading to successfully osseointegrated hip implants. Materials and methodsTwenty-four patients that had undergone primary total hip arthroplasty (THA) due to one-sided osteoarthritis (OA) were investigated during a period of 18 years (Y) with repeated measurements of plasma biomarkers as well as clinical and radiological variables. All implants were clinically and radiographically well anchored throughout the follow-up. Eighty-one healthy donors divided in three gender- and age-matched groups and twenty OA patients awaiting THA, served as controls. Plasma was analyzed for BMP-1, -2, -3, -4, -6, -7 -9 and TGF-β1, -β2, -β3 by use of a high-sensitivity and wide dynamic range electrochemiluminescence technique allowing for detection of minor changes. ResultsSpatiotemporal changes during the follow-up are presented in the context of the four phases of endochondral bone repair shown in earlier studies and transposed to the current study based on similarities in biomarker responses. Phase 1: Primary proinflammatory phase lasting from surgery until day 7, Phase 2: Chondrogenic phase from day 7 until 18 months postsurgery, Phase 3: Secondary proinflammatory and cartilage remodeling phase lasting from 18 months until 7Y, Phase 4: coupled bone remodeling from 7Y until 18Y postsurgery. BMP-1 increased sharply shortly after surgery and remained significantly above healthy during the chondrocyte recruitment, proliferation, and hypertrophy phases with a subsequent return to control level at 5Y postsurgery. BMP-2 was above healthy controls before surgery and 1 day after surgery before decreasing to control level and remaining there throughout the follow-up. BMP-3 was at control level from presurgery until 6M after surgery when it increased to a peak at 2Y during the cartilage hypertrophy phase followed by a gradual decrease to control level at 10Y during the phase of bone formation. In the following, BMP-3 decreased below controls to a nadir 15Y postsurgery during coupled bone remodeling. BMP-4 was at control level from presurgery until 10Y postsurgery when it increased to a sharp peak at 15Y after surgery followed by a return to the level of healthy at 18Y. BMP-6 did not differ from healthy during the follow-up. BMP-7 was at control level from presurgery until 1Y postsurgery before gradually increasing to a peak at 10Y during the early phase of osteogenesis with a gradual return to control level at 18Y during the phase of coupled bone remodeling. BMP-9 was above OA before surgery followed by a decrease to basal level on day 1 after surgery and a renewed increase to a plateau above controls lasting from 6 W until returning to the level of healthy at 18Y postsurgery, i.e., throughout the phases of cartilage formation, cartilage hypertrophy and remodeling, bone formation and coupled bone remodeling. TGF-β1 was above controls presurgery before decreasing to baseline shortly after surgery followed by a renewed increase at 6 M to a peak at 2Y during cartilage hypertrophy/remodeling followed by a gradual return to baseline at 10Y during early osteoblastogenesis. TGF-β2 was at control level from presurgery until the phase of cartilage remodeling at 5Y when it increased sharply to a peak at 7Y with a gradual return to baseline at 18Y postsurgery. TGF-β3 remained at control level throughout the study. ConclusionThis study shows that the involvement of BMPs and TGF-βs in endochondral bone repair is a process of stepwise recruitment of individual biomarkers characterized by distinct, yet overlaping, spatiotemporal patterns that extend from the early phase of pre-chondrocyte recruitment until the late phase of coupled bone remodeling.

Temperature-dependent photo-elastic coefficient of silicon at 1550 nm

This paper presents a study on the temperature dependent photo-elastic coefficient in single-crystal silicon with (100) and (110) orientations at a wavelength of 1550 nm. The measurement of the photo-elastic coefficient was performed using a polarimetric scheme across a wide temperature range from 5 to 300 K. The experimental setup employed high-sensitivity techniques and incorporated automatic beam path correction, ensuring precise and accurate determination of the coefficient’s values. The results show excellent agreement with previous measurements at room temperature, specifically yielding a value of dn/dsigma = -2.463 times 10^{-11} 1/Pa for the (100) orientation. Interestingly, there is a significant difference in photo-elasticity between the different crystal orientations of approximately 50%. The photo-elastic coefficient’s absolute value increases by approximately 40% with decreasing temperature down to 5 K. These findings provide valuable insights into the photo-elastic properties of silicon and its behavior under varying mechanical stress, particularly relevant for optomechanical precision experiments like cryogenic gravitational wave detectors and microscale optomechanical quantum sensors.

A comparison of methods of analysis of heavy metals in soil samples of Mitrovica environment, Republic of Kosovo

In this work, the distribution of heavy metals in surface soil samples (0-5 cm) from the MitrovicaRegion, was studied. The investigated region (301.5 km2) is covered by a sampling grid of 1.4×1.4 km. Intotal 156 soil samples from 149 locations were collected. Digestion methods, including Aqua RegiaDigestion (mixture of HNO3 and HCl and water at 95ºC - the 1DX1 method) and acid digestion: use ofconcentrated acids such as hydrofluoric acid (HF), hydrochloric acid (HCl), nitric acid (HNO3) andperchloric acid (HClO4) (ISO 14869- 1:2001(E) method), are used to prepare samples for spectroscopicanalysis. High-sensitivity spectroscopy techniques such as inductively coupled plasma emissionspectrometry (ICP-AES) and inductively coupled plasma mass spectrometry (ICP-MS) were applied tomeasure the concentration of Ni and Co in soil samples. Data analysis and construction of the map wereperformed using the Statistica (ver. 9), AutoDesk Map (ver. 2008) and Surfer (ver. 9) software. It was foundthat the average content of Ni and Co in the surface soil for the entire study area is 96 mg/kg (with a rangeof 7.6-2600 mg/kg) and 22 mg/kg (with a range of 2.7-1600 mg/kg), respectively. The obtained averageand median values obtained by ICP-MS are very similar to those obtained by ICP-AES. Namely, thecorrelation factor for Co and Ni between the results from both methods are 0.92 (for normal distribution),0.93 (for logarithmic) and 0.94 (for rank), and 0.86 (for normal distribution), 0.94 (for logarithmic) and0.96 (for rank), respectively. The obtained results show that the high concentrations of Ni and Co in thesurface soil samples may originate from similar sources and their distribution follows the lithology of thestudy area.

Wide-Bandwidth and High-Sensitivity Measurement Technique of Intrinsic Modulation Response of Semiconductor Lasers

Wide-Bandwidth and High-Sensitivity Measurement Technique of Intrinsic Modulation Response of Semiconductor Lasers

Biological Fluid Microsampling for Therapeutic Drug Monitoring: A Narrative Review.

Therapeutic drug monitoring (TDM) is a specialized area of laboratory medicine which involves the measurement of drug concentrations in biological fluids with the aim of optimizing efficacy and reducing side effects, possibly modifying the drug dose to keep the plasma concentration within the therapeutic range. Plasma and/or whole blood, usually obtained by venipuncture, are the "gold standard" matrices for TDM. Microsampling, commonly used for newborn screening, could also be a convenient alternative to traditional sampling techniques for pharmacokinetics (PK) studies and TDM, helping to overcome practical problems and offering less invasive options to patients. Although technical limitations have hampered the use of microsampling in these fields, innovative techniques such as 3-D dried blood spheroids, volumetric absorptive microsampling (VAMS), dried plasma spots (DPS), and various microfluidic devices (MDS) can now offer reliable alternatives to traditional samples. The application of microsampling in routine clinical pharmacology is also hampered by the need for instrumentation capable of quantifying analytes in small volumes with sufficient sensitivity. The combination of microsampling with high-sensitivity analytical techniques, such as liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS), is particularly effective in ensuring high accuracy and sensitivity from very small sample volumes. This manuscript provides a critical review of the currently available microsampling devices for both whole blood and other biological fluids, such as plasma, urine, breast milk, and saliva. The purpose is to provide useful information in the scientific community to laboratory personnel, clinicians, and researchers interested in implementing the use of microsampling in their routine clinical practice.