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Hierarchically Engineered Phage-Activated Click Interface for Ultra-Efficient Cell Capture.

Huida Li1, Rui Wang1, Fengting Jia1

  • 1Research Center for Analytical Sciences, Department of Chemistry, College of Sciences, Northeastern University, Box 332, Shenyang 110819, China.

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|December 27, 2025
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Summary
This summary is machine-generated.

This study introduces a novel multiscale cell capture interface (PACE-Chip) that significantly enhances cell binding strength and kinetics. The engineered chip efficiently isolates target cells from complex samples, outperforming traditional 2D methods.

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Area of Science:

  • Biomaterials Engineering
  • Cell Biology
  • Microfluidics

Background:

  • Efficient cell adhesion under flow is crucial for biological processes and artificial cell capture systems.
  • Existing methods primarily focus on molecular-level enhancements in 2D, neglecting multiscale strategies.
  • Simultaneous enhancement of cell-surface encounter frequency and binding probability across spatial scales is underexplored.

Purpose of the Study:

  • To develop a multiscale, hierarchically engineered cell capture interface for synergistic enhancement of cell binding.
  • To investigate the impact of integrating molecular, microscale, and macroscale features on cell capture efficiency.
  • To optimize phage scaffold length for improved cell capture performance.

Main Methods:

  • Engineered a multiscale hierarchically interface, PACE-Chip, integrating click chemistry, M13 phage scaffolds, and herringbone structures.
  • Evaluated binding strength and kinetics of the PACE-Chip against a 2D counterpart.
  • Assessed the efficiency of target cell isolation from complex blood matrices.
  • Analyzed the effect of phage length on binding performance.

Main Results:

  • The PACE-Chip demonstrated a 294% increase in binding strength and a 181-fold acceleration in binding kinetics.
  • Achieved highly efficient isolation of target cells down to the single-cell level from complex blood matrices.
  • Identified that excessive phage length negatively impacts performance due to entropic and structural penalties.

Conclusions:

  • The multiscale hierarchical engineering approach synergistically enhances cell binding kinetics and affinity.
  • PACE-Chip offers a superior platform for efficient cell isolation compared to traditional 2D interfaces.
  • A multiscale trade-off exists between multivalency and conformational stability, necessitating optimization of phage scaffold length.