Imaging of biological specimen is one of the most important tools to investigate structures and functionalities in organic components. Improving the resolution of images into the nanometer range call for short wavelengths light sources and large aperture optics. Subsequently, the use of extreme ultraviolet light in the range of 2 nm to 5 nm provides high contrast and high resolution imaging, if it is combined with lensless imaging techniques. We describe important parameters for high resolution lensless imaging of biological samples and specify the required light source properties. To overcome radiation based damage of biological specimen, we discuss the concept of ghost imaging and describe a possible setup towards biological imaging in the extreme ultraviolet range.
We evaluated the capabilities of an intense ultrafast high-harmonic seeded soft X-ray laser at 32.8 nm wavelength regarding single-shot lensless imaging and ptychography. Additionally the wave front at the exit of the laser plasma amplifier is monitored in amplitude and phase using high resolution ptychography and backpropagation techniques.Characterizing the laser plasma amplifier performance depending on the arrival time of the seed pulse with respect to pump pulses provides insight into the light plasma interaction in the soft X-ray range.
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.
In cancer treatment it is highly desirable to identify and /or classify individual cancer cells in real time. Nowadays, the
standard method is PCR which is costly and time-consuming. Here we present a different approach to rapidly classify
cell types: we measure the pattern of coherently diffracted extreme ultraviolet radiation (XUV radiation at 38nm
wavelength), allowing to distinguish different single breast cancer cell types. The output of our laser driven XUV light
source is focused onto a single unstained and unlabeled cancer cell, and the resulting diffraction pattern is measured in
reflection geometry. As we will further show, the outer shape of the object can be retrieved from the diffraction pattern
with sub-micron resolution. For classification it is often not necessary to retrieve the image, it is only necessary to
compare the diffraction patterns which can be regarded as a spatial fingerprint of the specimen. For a proof-of-principle
experiment MCF7 and SKBR3 breast cancer cells were pipetted on gold-coated silica slides. From illuminating each
single cell and measuring a diffraction pattern we could distinguish between them. Owing to the short bursts of coherent
soft x-ray light, one could also image temporal changes of the specimen, i.e. studying changes upon drug application
once the desired specimen is found by the classification method. Using a more powerful laser, even classifying
circulating tumor cells (CTC) at a high throughput seems possible. This lab-sized equipment will allow fast classification
of any kind of cells, bacteria or even viruses in the near future.
Light beams carrying an isolated point singularity with a screw-type phase distribution are called an optical vortex (OV). The fact that in free space the Poynting vector of the beam gives the momentum flow leads to an orbital angular momentum (OAM) of the photons in such a singular beam, independent on the spin angular momentun1. There are many applications of optical OAM shown in literature that would benefit from the availability of optical vortex beams in all spectral regions. For example it was shown that transitions forbidden by selection rules in dipole approximation appear allowed when using photons with the additional degree of freedom of optical OAM2. However, the common techniques of producing new light frequencies by nonlinear optical processes seem problematic in conserving the optical vortex when the nonlinearity becomes large. We show that with the extremely nonlinear process of High Harmonic Generation (HHG) it is possible to transfer OVs from the near-infrared to the extreme ultraviolet (XUV)3 at wavelengths down to ~30 nm. The observed XUV light was examined spatially and spectrally. The spatial profile showed the expected singular behavior, a dark region in the center. A comparison of the far-field fringe pattern caused by a thin wire with corresponding simulations suggests that the XUV vortex beam carries a unit topological charge. A screw-like phase evolution around the profile was also verified by employing a Hartmann type measurement. The generated spectrum revealed that in all Harmonic orders an OV was present. The profile, however, looked the same in all orders, indicating identical topological charge, which runs counterintuitive to the assumption that the phase of exp(–ilφ) is multiplied by the harmonic order in a frequency up-conversion experiment.