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Updated: Oct 29, 2025

Assembly of Nucleosomal Arrays from Recombinant Core Histones and Nucleosome Positioning DNA
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Deterministic assembly of chromosome ensembles in a programmable membrane trap array.

Hesam Babahosseini1,2, Darawalee Wangsa1, Mani Pabba2

  • 1National Cancer Institute, National Institutes of Health, Bethesda, MD, United States of America.

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Summary

This study presents a microfluidic system for precisely isolating and manipulating single chromosomes. It enables the controlled assembly of chromosome ensembles for advanced genetic engineering and synthetic biology applications.

Keywords:
chromosome manipulationdropletsynthetic biology

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Area of Science:

  • Biotechnology
  • Microfluidics
  • Genomics

Background:

  • Precise manipulation of individual chromosomes is crucial for genetic engineering and synthetic biology.
  • Existing methods lack the resolution and control for forming defined chromosome ensembles.

Purpose of the Study:

  • To develop a microfluidic system for selective spatial isolation and manipulation of single chromosomes.
  • To demonstrate the controlled formation of defined chromosome ensembles using this technology.

Main Methods:

  • A droplet-based microfluidic system utilizing elastomer valves and membrane displacement traps.
  • Self-discretization of sample plugs into picoliter droplets within a 2D array of microscale traps.
  • Optical interrogation and selective droplet release for sequential delivery to a merging zone.

Main Results:

  • Demonstrated deterministic manipulation of individual droplets with single macromolecule resolution.
  • Successfully achieved co-compartmentalization of three chromosome pairs.
  • Enabled efficient manipulation of multiple chromosomes into defined ensembles.

Conclusions:

  • The developed microfluidic technology offers precise control over chromosome manipulation and ensemble formation.
  • This system is a foundational step towards creating custom chromosome sets for synthetic biology and genetic engineering.
  • The technology facilitates advanced applications requiring defined chromosome compositions.