Cancer cell classification with coherent diffraction imaging using an extreme ultraviolet radiation source

Abstract

Abstract. In cancer treatment, it is highly desirable to classify single cancer cells in real time. The standard method is polymerase chain reaction requiring a substantial amount of resources and time. Here, we present an innovative approach for rapidly classifying different cell types: we measure the diffraction pattern of a single cell illuminated with coherent extreme ultraviolet (XUV) laser-generated radiation. These patterns allow distinguishing different breast cancer cell types in a subsequent step. Moreover, the morphology of the object can be retrieved from the diffraction pattern with submicron resolution. In a proof-of-principle experiment, we prepared single MCF7 and SKBR3 breast cancer cells on gold-coated silica slides. The output of a laser-driven XUV light source is focused onto a single unstained and unlabeled cancer cell. With the resulting diffraction pattern, we could clearly identify the different cell types. With an improved setup, it will not only be feasible to classify circulating tumor cells with a high throughput, but also to identify smaller objects such as bacteria or even viruses.

Real-time and Sub-wavelength Ultrafast Coherent Diffraction Imaging in the Extreme Ultraviolet

“…Nevertheless, there are applications where the diffraction pattern is directly assessed, e.g. the recently demonstrated CDI based cancer cell classification 22 .…”

“…The XUV focal spot has an FWHM diameter of less than 5 µm, measured by scanning a 2 µm aperture across the beam profile in the focal plane. The few micron focal spot size is ideally suited to image single biologic specimen such as, e.g., breast cells with nanometer resolution while preserving a sufficiently large field-of-view 22 .…”

Extremely Nonlinear Optics Using Shaped Pulses Spectrally Broadened in an Argon- or Sulfur Hexafluoride-Filled Hollow-Core Fiber

“…Using shaped driving laser fields is also a promising way to increase the HHG conversion efficiency. The high average power of optimized HHG sources allow now coherent diffraction imaging [6] which paves the way for using HHG sources for biological and medical applications [7], especially bearing in mind the ongoing effort to push HHG into the water window [8,9]. Two major scaling laws render HHG difficult for practical applications, namely:…”

Online Monitoring of Laser-Generated XUV Radiation Spectra by Surface Reflectivity Measurements with Particle Detectors

“…Due to the spectral, spatial, and temporal properties of HHG radiation, its applications range from fundamental atomic and molecular physics to material science, biology, and medicine [1][2][3], and great effort is being put into further source development [4][5][6] and scaling to high repetition rates and high laser pulse energies [7,8]. Since high-order harmonics are generated from an infrared laser pulse by nonlinear interaction with a gaseous medium, one task is to filter out the fundamental infrared beam to ensure a pure interaction of the sample with XUV radiation [9][10][11].…”