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Yuhao Wang1, Xuejiao Wang1, Zihan Cai1

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Summary
This summary is machine-generated.

Researchers developed novel covalent organic frameworks (COFs) for simultaneous capture and separation of nucleic acids and proteins from liquid biopsies. This breakthrough enables comprehensive multiomics profiling from urine samples.

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Area of Science:

  • Materials Science
  • Biochemistry
  • Analytical Chemistry

Background:

  • Efficient multiomics profiling from liquid biopsies requires simultaneous capture and separation of nucleic acids and proteins.
  • Current methods are limited by the lack of suitable materials for this complex task.

Purpose of the Study:

  • To design and characterize covalent organic frameworks (COFs) for the simultaneous capture and stepwise separation of nucleic acids and proteins.
  • To elucidate the binding mechanisms and thermodynamic drivers for ssDNA and protein adsorption onto COFs.
  • To develop a solvent-mediated strategy for orthogonal release of captured analytes.

Main Methods:

  • Synthesis and characterization of covalent organic frameworks (COFs) with tunable pore sizes.
  • Isothermal titration calorimetry (ITC) and molecular dynamics (MD) simulations to investigate binding thermodynamics.
  • Solvent-mediated elution strategies to achieve sequential release of nucleic acids and proteins.
  • Application of the COF platform for enrichment of cell-free DNA, cell-free RNA, and proteins from urine samples.

Main Results:

  • A COF with a 3.9 nm pore size was identified, exhibiting maximal affinity for both single-stranded DNA (ssDNA) and proteins.
  • ssDNA adsorption is primarily entropy-driven, while protein binding is driven by entropy-enthalpy synergy, creating distinct affinities.
  • A solvent-mediated strategy enabled mild, sequential desorption of nucleic acids and proteins from the COF interface.
  • The COF platform demonstrated superior performance in high-fidelity enrichment of low-abundance analytes from urine.

Conclusions:

  • The developed COF platform offers a versatile solution for simultaneous capture and orthogonal release of nucleic acids and proteins.
  • This approach significantly advances the field of liquid biopsy for comprehensive multiomics profiling.
  • The mechanistic insights into binding thermodynamics guided the rational design of the COF material and elution strategy.