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DNA-Programmed Orientation-Ordered Multivalent Microfluidic Interface for Liquid Biopsy.

Jiao Peng1, Yilong Liu1, Rui Su2

  • 1MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, State Key Laboratory of Physical Chemical of Solid Surfaces, Key Laboratory for Chemical Biology of Fujian Province, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China.

Analytical Chemistry
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Summary
This summary is machine-generated.

This study introduces a novel DNA nanostructure strategy for precisely orienting aptamers on microfluidic chips. This enhances circulating tumor cell capture and release for improved liquid biopsy diagnostics.

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Area of Science:

  • Biotechnology
  • Nanotechnology
  • Medical Diagnostics

Background:

  • Aptamer-functionalized microfluidic devices show promise for liquid biopsies.
  • Previous designs often overlook aptamer orientation, limiting binding efficiency.
  • Optimizing aptamer arrangement is crucial for enhanced affinity and accessibility.

Purpose of the Study:

  • To develop a DNA nanostructure-programmed strategy for precise aptamer orientation and valency control on microfluidic interfaces.
  • To enhance the capture and release of circulating tumor cells (CTCs) using this novel approach.
  • To demonstrate the clinical utility of the developed aptamer-based microfluidic chip for leukemia detection and downstream analysis.

Main Methods:

  • Utilized a DNA nanostructure-programmed strategy to create an ordered aptamer configuration on a microfluidic interface (CDN-Apt-Chip).
  • Evaluated the synergistic effect of ordered orientation and multivalent aptamer configuration on binding affinity towards CTCs.
  • Applied the CDN-Apt-Chip for isolating CTCs from leukemia patient blood, discriminating patients from healthy volunteers, and enabling non-destructive cell release.

Main Results:

  • The ordered aptamer orientation and multivalent configuration significantly increased binding affinity for CTCs.
  • Successfully isolated CTCs from peripheral blood of T-cell leukemia patients.
  • Demonstrated the ability to discriminate T-cell leukemia patients from healthy individuals.
  • Achieved non-destructive release of captured CTCs using nuclease treatment.
  • Confirmed compatibility of released CTCs with downstream T-cell receptor sequencing.

Conclusions:

  • The DNA nanostructure-programmed strategy offers precise control over aptamer orientation and valency on microfluidic chips.
  • This approach enhances CTC capture and release, advancing aptamer-based liquid biopsy.
  • The CDN-Apt-Chip represents a new paradigm for interface regulation in microfluidic devices, facilitating clinical translation.