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PreprintCC BY-NDbioRxiv

ART: A Compositional Physical Theory for the End-to-End Design of Solid-Phase Immunosensors

  1. 1Shenzhen Institute of Advanced Technology, Chinese Academy of Science

Abstract

Predicting complete solid phase immunoassay performance remains challenging because antibody recognition, reactor transport, molecular transduction and physical observation are coupled rather than independent. Here, we formulate ART as a compositional physical theory expressed as Y = Ts[Tm[AR(X)]]. Recognition A and reactor transport R jointly determine the retained molecular state, while molecular transduction Tm and physical observation Ts operate through replaceable interfaces. Finite-time kinetic and reaction diffusion calculations across plate, tubular and bead formats show that antibodies with identical dissociation constants can produce different capture responses because of distinct association and dissociation rates. In fixed-length tubular reactors, mass-conserving transport distinguishes surface capture density from fractional recovery, revising a first-passage-based local density optimum while preserving a multicriterion design window. An AR-only concentration-threshold map identifies when recognition kinetics or reactor redesign offers greater local leverage. The benefits of improved affinity also depend on the kinetic pathway and reactor regime. For enzymatic transduction, we propose a four-parameter, substrate-conserving model in which the saturation-shape parameter is hm = KM/S0 under a one effective substrate approximation. Accumulated TMB color and time-dependent luminol emission represent distinct consequences of reaction progress, while Ts describes measurement limits through a simplified floor slope roof model. ELISA with OD450 readout and tubular chemiluminescence with camera detection illustrate the end-to-end framework. These examples remain conditional model demonstrations, and existing complete chain curves have not yet been recalibrated using the new enzyme model. ART provides a modular quantitative framework for assay design based on explicit physical interfaces and coupled processes.

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BibTeX
@misc{zhang2026compositional,
  title = {{ART: A Compositional Physical Theory for the End-to-End Design of Solid-Phase Immunosensors}},
  author = {J. Zhang and T. Zhao and H. Li and X. Tan},
  howpublished = {bioRxiv},
  year = {2026},
  month = oct,
  doi = {10.64898/2026.10.27.762221},
  url = {https://www.biorxiv.org/content/10.64898/2026.10.27.762221v1},
  note = {CC BY-ND},
}
RIS
TY  - UNPB
TI  - ART: A Compositional Physical Theory for the End-to-End Design of Solid-Phase Immunosensors
AU  - J. Zhang
AU  - T. Zhao
AU  - H. Li
AU  - X. Tan
PY  - 2026
DA  - 2026/10/27
PB  - bioRxiv
DO  - 10.64898/2026.10.27.762221
UR  - https://www.biorxiv.org/content/10.64898/2026.10.27.762221v1
AB  - Predicting complete solid phase immunoassay performance remains challenging because antibody recognition, reactor transport, molecular transduction and physical observation are coupled rather than independent. Here, we formulate ART as a compositional physical theory expressed as Y = Ts[Tm[AR(X)]]. Recognition A and reactor transport R jointly determine the retained molecular state, while molecular transduction Tm and physical observation Ts operate through replaceable interfaces. Finite-time kinetic and reaction diffusion calculations across plate, tubular and bead formats show that antibodies with identical dissociation constants can produce different capture responses because of distinct association and dissociation rates. In fixed-length tubular reactors, mass-conserving transport distinguishes surface capture density from fractional recovery, revising a first-passage-based local density optimum while preserving a multicriterion design window. An AR-only concentration-threshold map identifies when recognition kinetics or reactor redesign offers greater local leverage. The benefits of improved affinity also depend on the kinetic pathway and reactor regime. For enzymatic transduction, we propose a four-parameter, substrate-conserving model in which the saturation-shape parameter is hm = KM/S0 under a one effective substrate approximation. Accumulated TMB color and time-dependent luminol emission represent distinct consequences of reaction progress, while Ts describes measurement limits through a simplified floor slope roof model. ELISA with OD450 readout and tubular chemiluminescence with camera detection illustrate the end-to-end framework. These examples remain conditional model demonstrations, and existing complete chain curves have not yet been recalibrated using the new enzyme model. ART provides a modular quantitative framework for assay design based on explicit physical interfaces and coupled processes.
ER  -