The Mitra Microsampling User Guide

Importance of the Topic

The ability to collect precise, small-volume biological samples in a reproducible and user-friendly manner is transforming bioanalytical workflows. Volumetric absorptive microsampling (VAMS) with Mitra® devices enables accurate, fixed-volume capture (<50 µL) of blood and other matrices for off-site collection, ambient transport, and long-term storage without cold chain. This approach reduces logistical complexity, supports remote or resource-limited studies, and facilitates quantitative analysis across diverse analytes and instruments.

Study Overview

This guide synthesizes best practices from nearly 200 peer-reviewed publications to outline considerations for selecting sampling volumes, preparing microsamples, managing matrix effects, and optimizing extraction protocols. It provides a roadmap for initial method development, validation planning, and practical implementation in research laboratories.

Methodology and Instrumentation

Microsample processing typically begins with protective Mitra housings (cartridge or clamshell) and transfer into a 96-Autorack™ for high-throughput extraction.

• Organic extractions: Water-miscible solvents (e.g., methanol, ethyl acetate mixes) with pH adjustment maximize recovery of small molecules by disrupting ionic and hydrophobic interactions.
• Aqueous extractions: Buffered systems (PBS, surfactants, proteinase K) and protein precipitation (e.g., ZnSO₄ or organic solvents) suit larger biomolecules, immunoassays, or nucleic acid analysis.
• Mechanical aids: Vortexing, sonication, and impact-assisted extraction can further enhance desorption efficiency.

Instrumentation Used

• LC-MS/MS (triple quadrupole, TOF)
• GC-MS
• ICP-MS
• HPLC with non-MS detectors (UV, fluorescence)
• Immunoassay platforms
• Biochemistry analyzers
• qPCR and next-generation sequencing

Main Findings and Discussion

Key analytical challenges include matrix effects, ion suppression, extraction recovery, hematocrit bias, and temporal stability. Systematic evaluation using pre- and post-spike experiments quantifies matrix suppression and process efficiency. Hematocrit and sample age must be simulated at extremes to ensure robust recoveries above 85%. pH modifiers and solvent selection tailored to analyte logP significantly improve extraction yields. On-tip protein precipitation simplifies workflows and automates high-throughput assays.

Benefits and Practical Applications

• Eliminates cold storage/shipping, reducing cost and logistical barriers.
• Enables remote or decentralized sampling and patient self-collection.
• Supports quantitative analysis of drugs, biomarkers, metals, proteins, and nucleic acids.
• Facilitates high-throughput workflows in clinical, pharmaceutical, and research settings.

Future Trends and Applications

Emerging areas include integration with automated liquid handlers, miniaturized mass spectrometers, digital health platforms for real-time monitoring, and expanded panels of multiplexed biomarker assays. Continued innovations in sorbent chemistries and in-tip derivatization will further extend the range of compatible analytes.

Conclusion

Volumetric absorptive microsampling with Mitra devices offers a versatile, scalable solution for modern bioanalysis. By following structured extraction optimization, matrix-effect evaluation, and validation strategies, laboratories can achieve robust, reproducible assays across diverse analyte classes and instrumentation.

References

1. Ji QC et al. Journal of Bioanalytical Methods, 2021.
2. Basdeo S and Discenza L. Bioanalysis, 2020.
3. D’Arienzo C et al. Analytical Chemistry, 2019.
4. Olah TV. Clinical Chemistry, 2018.
5. Arnold ME. Therapeutic Drug Monitoring, 2017.