Using Fourier ptychography microscopy to achieve high-resolution chromosome imaging: an initial evaluation

J Biomed Opt. 2022 Jan;27(1):016504. doi: 10.1117/1.JBO.27.1.016504.

Abstract

Significance: Searching analyzable metaphase chromosomes is a critical step for the diagnosis and treatment of leukemia patients, and the searching efficiency is limited by the difficulty that the conventional microscopic systems have in simultaneously achieving high resolution and a large field of view (FOV). However, this challenge can be addressed by Fourier ptychography microscopy (FPM) technology.

Aim: The purpose of this study is to investigate the feasibility of utilizing FPM to reconstruct high-resolution chromosome images.

Approach: An experimental FPM prototype, which was equipped with 4 × / 0.1 NA or 10 × / 0.25 NA objective lenses to achieve a theoretical equivalent NA of 0.48 and 0.63, respectively, was developed. Under these configurations, we first generated the system modulation transfer function (MTF) curves to assess the resolving power. Next, a group of analyzable metaphase chromosomes were imaged by the FPM system, which were acquired from the peripheral blood samples of the leukemia patients. The chromosome feature qualities were evaluated and compared with the results accomplished by the corresponding conventional microscopes.

Results: The MTF curve results indicate that the resolving power of the 4 × / 0.1 NA FPM system is equivalent and comparable to the 20 × / 0.4 NA conventional microscope, whereas the performance of the 10 × / 0.25 NA FPM system is close to the 60 × / 0.95 NA conventional microscope. When imaging the chromosomes, the feature qualities of the 4 × / 0.1 NA FPM system are comparable to the results under the conventional 20 × / 0.4 NA lens, whereas the feature qualities of the 10 × / 0.25 NA FPM system are better than the conventional 60 × / 0.95 NA lens and comparable to the conventional 100 × / 1.25 NA lens.

Conclusions: This study initially verified that it is feasible to utilize FPM to develop a high-resolution and wide-field chromosome sample scanner.

Keywords: Fourier ptychography microscopy; analyzable metaphase chromosome; high throughput scanning; leukemia diagnosis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Chromosomes
  • Fourier Analysis
  • Humans
  • Lenses*
  • Microscopy* / methods