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Matrix-assisted laser desorption ionization (MALDI) is a powerful analytical technique used in mass spectrometry. It enables the identification and characterization of various biomolecules, including proteins, peptides, nucleic acids, and carbohydrates. MALDI is an ionization technique, widely employed in biological and medical research, as well as in fields like pharmacology and biochemistry.The analyte of interest, a biomolecule or a mixture of biomolecules, is mixed with a suitable matrix...

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Label-Free Dynamic Single-Molecule Sensing of Alpha-2-Macroglobulin in Complex Matrices.

Qichuan Jiang1, Qiang Zeng2, Haiyang Yu3

  • 1Otolaryngology Head and Neck surgery Department, the First Affiliated Hospital of JinZhou Medical University, JinZhou 121001, China.

ACS Sensors
|September 9, 2025
PubMed
Summary
This summary is machine-generated.

We developed a novel label-free dynamic single-molecule sensing method for accurate Alpha-2-macroglobulin (A2M) detection. This sensitive technique offers a promising tool for quantifying A2M in complex biological samples like serum.

Keywords:
alpha-2-macroglobulinbiomarker profilingdynamic single-molecule sensingkinetic filteringlabel-free detection

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Area of Science:

  • Biomarker Discovery
  • Analytical Chemistry
  • Molecular Diagnostics

Background:

  • Alpha-2-macroglobulin (A2M) is a key biomarker in inflammation, immunity, coagulation, and diseases like fibrosis, neurodegeneration, and cancer.
  • Accurate A2M quantification is challenging due to its dynamic nature, low abundance variations, and interference from other plasma proteins.

Purpose of the Study:

  • To introduce a novel label-free dynamic single-molecule sensing (LFDSMS) strategy for sensitive and specific A2M detection.
  • To overcome the limitations of existing methods for A2M quantification in complex biological fluids.

Main Methods:

  • Utilized a label-free dynamic single-molecule sensing (LFDSMS) platform monitoring real-time, reversible antibody-A2M interactions.
  • Optimized buffer ionic strength to enhance binding-dissociation kinetics for signal amplification.
  • Employed surface-immobilized antibodies for specific capture and detection of A2M.

Main Results:

  • Achieved a limit of detection of 25 ± 2 ng/mL in undiluted serum and 29 ± 4 ng/mL in cell culture medium.
  • Demonstrated high specificity for A2M detection even in complex biological matrices.
  • Showed excellent correlation with ELISA (R² = 0.988), confirming method's reliability.

Conclusions:

  • LFDSMS provides a sensitive, specific, and robust method for A2M quantification.
  • This technique holds significant potential for quantitative biomarker profiling in clinical settings.
  • The optimized LFDSMS platform addresses current challenges in A2M measurement.