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Redefining antibody cross-reactivity as an advantage for sensing and diagnostics
Josselyn Mata Calidonio1, Kimberly Hamad-Schifferli1
1Department of Engineering, School for the Environment, University of Massachusetts Boston, Boston, MA, USA.
Trends in Biotechnology
|June 19, 2025
Summary
Antibody cross-reactivity, often seen as a flaw, can be a powerful tool in biosensing arrays. Strategic use of this property enables complex sample analysis and scalable multiplexed detection.
Area of Science:
- Biochemistry
- Analytical Chemistry
- Biosensing Technology
Background:
- Antibody specificity is traditionally prioritized, with cross-reactivity considered an undesirable trait leading to assay interference.
- Existing efforts focus on minimizing antibody cross-reactivity to enhance assay precision and reduce crosstalk.
Purpose of the Study:
- To re-evaluate the role of antibody cross-reactivity, proposing its strategic exploitation in biosensing.
- To explore the potential of using antibody cross-reactivity in array formats, analogous to chemolfactory arrays.
Main Methods:
- Conceptual framework based on chemometric and chemolfactory array principles.
- Analysis of how cross-reactive antibody arrays can distinguish complex samples.
Main Results:
- Cross-reactivity can be a significant strength when antibodies are employed in selective arrays.
- The ability of antibodies to bind multiple antigens can be leveraged for powerful, complex sample analysis.
Conclusions:
- Exploiting antibody cross-reactivity offers a unique opportunity to transform biosensing capabilities.
- This approach can lead to scalable, cost-effective, and adaptable tools for multiplexed detection, particularly in time-sensitive applications.
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