Towards virtual histology with X-ray grating interferometry.

Breast cancer is the most common type of cancer worldwide. Diagnosing breast cancer relies on clinical examination, imaging and biopsy. A core-needle biopsy enables a morphological and biochemical characterization of the cancer and is considered the gold standard for breast cancer diagnosis. A histopathological examination uses high-resolution microscopes with outstanding contrast in the 2D plane, but the spatial resolution in the third, Z-direction, is reduced. In the present paper, we propose two high-resolution table-top systems for phase-contrast X-ray tomography of soft-tissue samples. The first system implements a classical Talbot-Lau interferometer and allows to perform ex-vivo imaging of human breast samples with a voxel size of 5.57 µm. The second system with a comparable voxel size relies on a Sigray MAAST X-ray source with structured anode. For the first time, we demonstrate the applicability of the latter to perform X-ray imaging of human breast specimens with ductal carcinoma in-situ. We assessed image quality of both setups and compared it to histology. We showed that both setups made it possible to target internal features of breast specimens with better resolution and contrast than previously achieved, demonstrating that grating-based phase-contrast X-ray CT could be a complementary tool for clinical histopathology.

Bottom-Up Gold Filling in New Geometries and Yet Higher Aspect Ratio Gratings for Hard X-Ray Interferometry.

An extreme bottom-up filling variant of superconformal Au electrodeposition yielding void-free filling of recessed features is demonstrated with diffraction gratings composed of a two-dimensional patterned "chessboard" array of square vias of aspect ratio (depth/width) ≈ 23 as well as one-dimensional arrays of trenches having aspect ratios exceeding 50 and 65. Deposition on planar and patterned substrates is examined in several near-neutral x mol·L-1 Na3Au(SO3)2 + 0.64 mol·L-1 Na2SO3 electrolytes (x = [0.08, 0.16, 0.32]) containing ≈ 50 µmol·L-1 Bi3+ additive. The electrolytes are similar to those used in earlier work, although the upper bound on Au(SO3)2 concentration is twofold greater than previously described. Filling results are complemented by associated current and deposition charge transients whose features, particularly with well controlled pH, exhibit repeatable behaviors and timescales for incubation of passive deposition followed by bottom-up, void-free filling. While incompletely filled features can exhibit substantial via-to-via variation in fill height, self-passivation that follows complete bottom-up filling results in highly uniform filling profiles across the substrates. Visibility measurements capture the quality and uniformity of the as-formed wafer scale gratings. X-ray phase contrast imaging demonstrates their potential for imaging applications.

Scanning transmission X-ray microscopy with a fast framing pixel detector.

Scanning transmission X-ray microscopy (STXM) is a powerful imaging technique, in which a small X-ray probe is raster scanned across a specimen. Complete knowledge of the complex-valued transmission function of the specimen can be gained using detection schemes whose every-day use, however, is often hindered by the need of specialized configured detectors or by slow or noisy readout of area detectors. We report on sub-50 nm-resolution STXM studies in the hard X-ray regime using the PILATUS, a fully pixelated fast framing detector operated in single-photon counting mode. We demonstrate a range of imaging modes, including phase contrast and dark-field imaging.

Colloidal monolayer trapped near a charged wall: a synchrotron x-ray diffraction study.

Using x-ray diffraction from microfluidic channel arrays, we have determined concentration profiles of charge-stabilized silica colloids (radius 60+/-2 nm) confined between two like-charged dielectric walls at a few hundred nanometer distance. In solutions of very low ionic strength, strongly repulsive Coulomb interactions drive the colloids toward the central region between the walls. The addition of a small quantity of salt ions (0.2 mM) causes a dense colloidal monolayer to be trapped near the walls.

Coherent diffractive imaging using phase front modifications.

We introduce a coherent diffractive imaging technique that utilizes multiple exposures with modifications to the phase profile of the transmitted wave front to compensate for the missing phase information. This is a single spot technique sensitive to both the transmission and phase shift through the sample. Along with the details of the method, we present results from the first proof of principle experiment. The experiment was performed with 6.0 keV x rays, in which an estimated spatial resolution of 200 nm was achieved.

Hard-x-ray lensless imaging of extended objects.

We demonstrate a hard-x-ray microscope that does not use a lens and is not limited to a small field of view or an object of finite size. The method does not suffer any of the physical constraints, convergence problems, or defocus ambiguities that often arise in conventional phase-retrieval diffractive imaging techniques. Calculation times are about a thousand times shorter than in current iterative algorithms. We need no a priori knowledge about the object, which can be a transmission function with both modulus and phase components. The technique has revolutionary implications for x-ray imaging of all classes of specimen.

Zone-doubling technique to produce ultrahigh-resolution x-ray optics.

A method for the fabrication of ultrahigh-resolution Fresnel zone plate lenses for x-ray microscopy is demonstrated. It is based on the deposition of a zone plate material (Ir) onto the sidewalls of a prepatterned template structure (Si) using an atomic layer deposition technique. This results in a doubling of the effective zone density, thus improving the achievable resolution of x-ray microscopes. Test structures with lines and spaces down to 15 nm were resolved in a scanning transmission x-ray microscope at 1 keV photon energy.