System and method for x-ray fluorescence with filtering

Abstract

An x-ray optical filter includes at least one x-ray optical mirror configured to receive a plurality of x-rays having a first x-ray spectrum with a first intensity as a function of energy in a predetermined solid angle range and to separate at least some of the received x-rays by multilayer reflection or total external reflection into reflected x-rays and non-reflected x-rays and to form an x-ray beam including at least some of the reflected x-rays and/or at least some of the non-reflected x-rays. The x-ray beam has a second x-ray spectrum with a second intensity as a function of energy in the solid angle range, the second intensity greater than or equal to 50% of the first intensity across a first continuous energy range at least 3 keV wide, the second intensity less than or equal to 10% of the first intensity across a second continuous energy range at least 100 eV wide.

Description

BACKGROUND

Field

This application relates generally to laboratory-based x-ray fluorescence analysis systems and methods.

Description of the Related Art

In x-ray fluorescence (XRF) analysis using laboratory x-ray sources, a major limitation in the detection and quantification of trace elements is the background contribution due to elastic and inelastic (Compton) scattering of the incident x-rays reaching and being detected by the x-ray detector. This background contribution extends across an energy range that overlaps with the energies of the x-ray fluorescence lines of interest, and is an important source of noise that reduces the signal-to-noise ratio of the x-ray detector.

In some conventional XRF systems, this background contribution is reduced by transmitting the incident x-ray beam through one or more thin foil filters to attenuate the x-rays incident on the sample in the energy range of the x-ray fluorescence lines of interest. However, such transmission filters tend to be effective only over a relatively narrow energy range immediately above the absorption edge of the filter material. In addition, such transmission filters also attenuate the higher energy bremsstrahlung x-rays from reaching the sample and exciting the x-ray fluorescence lines, thereby diminishing the desired x-ray fluorescence signal. In other conventional XRF systems, the background contribution is filtered from the incident x-ray energy spectrum by reflecting the incident x-ray beam from a multilayer-coated surface (e.g., mirror; monochromator) which selectively reflects x-rays within a corresponding energy range and transmits x-rays outside the corresponding energy range. The reflected x-rays are directed to illuminate the sample, while transmitted x-rays propagate away from the sample and the x-ray detector.

SUMMARY

In one aspect disclosed herein, an x-ray optical filter comprises at least one x-ray optical mirror. The at least one x-ray optical mirror is configured to receive a plurality of x-rays having a first x-ray spectrum with a first intensity as a function of energy in a predetermined solid angle range and to separate at least some of the received x-rays by multilayer reflection or total external reflection into reflected x-rays and non-reflected x-rays and to form an x-ray beam comprising at least some of the reflected x-rays and/or at least some of the non-reflected x-rays. The x-ray beam has a second x-ray spectrum with a second intensity as a function of energy in the solid angle range, the second intensity greater than or equal to 50% of the first intensity across a first continuous energy range at least 3 keV wide, the second intensity less than or equal to 10% of the first intensity across a second continuous energy range at least 100 eV wide.

In another aspect disclosed herein, a method of performing x-ray fluorescence analysis is provided. The method comprises receiving x-rays having a first energy spectrum and a first spatial distribution. The method further comprises reflecting at least some of the received x-rays, the reflected x-rays having a second energy spectrum and a second spatial distribution. The method further comprises separating the reflected x-rays by multilayer reflection and/or total external reflection into a first portion that impinges a sample and a second portion having a predetermined range of x-ray energies, the first portion having a third energy spectrum that has a reduced intensity, as compared to the second energy spectrum, in the predetermined range of x-ray energies.

In another aspect disclosed herein, an x-ray system comprises at least one first x-ray optical mirror configured to receive at least a portion of a first x-ray beam having a first energy spectrum and to reflect at least some of the x-rays of the portion of the first x-ray beam to form a second x-ray beam. The x-ray system further comprises at least one second x-ray optical mirror comprising at least one mosaic crystal layer, at least one depth-grated multilayer reflector, and/or at least one grazing incidence mirror. The at least one second x-ray optical mirror is configured to receive at least some of the x-rays from the at least one first x-ray optical mirror, to transmit a second x-ray beam comprising a transmitted portion of the x-rays received from the at least one first x-ray optical mirror, and to reflect a reflected portion of the x-rays received from the at least one first x-ray optical mirror. The second x-ray beam has a second energy spectrum with a reduced intensity, as compared to the first energy spectrum, in a predetermined range of x-ray energies.

In another aspect disclosed herein, an x-ray system comprises at least one x-ray source configured to generate x-rays. The x-ray system further comprises at least one x-ray optical element configured to receive and focus at least some of the x-rays from the at least one x-ray source. The at least one x-ray optical element comprises at least one substrate comprising a surface and at least one depth-graded multilayer coating on the surface. The at least one depth-graded multilayer coating is configured to substantially reflect x-rays having energies in a first energy range and to not substantially reflect x-rays having energies in a second energy range that does not overlap the first energy range.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows examples of biologically important elements detectable using hard x-rays in accordance with certain embodiments described herein (from M. J. Pushie et al., “Elemental and chemically specific x-ray fluorescence imaging of biological systems,” Chemical Reviews 114:17 (2014): 8499-8541).

FIGS. 2A-2D schematically illustrate various example x-ray optical systems in accordance with certain embodiments described herein.

FIG. 3A schematically illustrates an example x-ray optical system in accordance with certain embodiments described herein.

FIG. 3B schematically illustrates an example at least one substrate of the x-ray focusing optical element of FIG. 3A in accordance with certain embodiments described herein.

FIG. 3C schematically illustrates an example at least one layer of the x-ray focusing optical element of FIG. 3A in accordance with certain embodiments described herein.

FIG. 4A schematically illustrates an example idealized x-ray spectrum of an electron impact x-ray source in a predetermined solid angle range with an idealized conventional foil-filtered Au target spectrum in the solid angle range.

FIG. 4B schematically illustrates an example idealized x-ray spectrum of an electron impact x-ray source in a predetermined solid angle range with an idealized “notch”-filtered Au target x-ray spectrum in the solid angle range in accordance with certain embodiments described herein.

FIG. 5A shows two example x-ray spectra reflected from the downstream end of an ellipsoidal portion of an x-ray focusing optical element with an incidence angle of 16.7 mrad (0.93 degree) for 4.5 nm and 3 nm d-spacings, respectively, in accordance with certain embodiments described herein.

FIG. 5B shows two example x-ray spectra reflected from the upstream end of an ellipsoidal portion of an x-ray focusing optical element with an incidence angle of 12.5 mrad (0.72 degree) for 4.5 nm and 3 nm d-spacings, respectively, in accordance with certain embodiments described herein.

FIG. 6 shows a table of the K-line x-ray fluorescence cross sections of Fe, Cu, and Zn at four x-ray excitation energies in accordance with certain embodiments described herein.

FIG. 7 shows the suppression of unwanted background under the P and S K-line fluorescence using a 5 mm thick Si filter in accordance with certain embodiments described herein.

FIGS. 8A-8D schematically illustrates various other examples of the x-ray optical system in accordance with certain embodiments described herein.

FIG. 9A schematically illustrates a cross-sectional view of an example first x-ray optical element comprising at least one capillary tube in accordance with certain embodiments described herein.

FIG. 9B schematically illustrates an example first x-ray energy spectrum of the first x-ray beam in accordance with certain embodiments described herein.

FIG. 10A schematically illustrates an example system in which the at least one second x-ray optical element comprises at least one x-ray reflector in accordance with certain embodiments described herein.

FIG. 10B schematically illustrates an example second x-ray energy spectrum of the second x-ray beam of FIG. 10A in accordance with certain embodiments described herein.

FIG. 11A schematically illustrates an example system in which the at least one second x-ray optical element comprises a plurality of x-ray reflectors in accordance with certain embodiments described herein.

FIG. 11B schematically illustrates an example second x-ray energy spectrum of the second x-ray beam of FIG. 11A in accordance with certain embodiments described herein.

FIG. 12A schematically illustrates an example system in which the at least one x-ray reflector comprises at least one grazing incidence mirror in accordance with certain embodiments described herein.

FIG. 12B schematically illustrates an example second x-ray energy spectrum of the second x-ray beam of FIG. 12A in accordance with certain embodiments described herein.

FIG. 13A schematically illustrates an example system comprising a first x-ray reflector and a second x-ray reflector in accordance with certain embodiments described herein.

FIG. 13B schematically illustrates an example second x-ray energy spectrum of the second x-ray beam and the x-rays reflected from the second x-ray reflector of FIG. 13A in accordance with certain embodiments described herein.

FIG. 14 is a flow diagram of an example method of performing x-ray fluorescence analysis in accordance with certain embodiments described herein.

DETAILED DESCRIPTION

One example area in which x-ray fluorescence (XRF) can provide information is the interactions of metals in biological systems (e.g., role of metals in biological processes; metal-based drugs). These trace elements are typically found in concentration of parts per million (ppm) and spatially specific at organ, tissue, cell, and sub-cellular levels. Abnormal trace element distribution in tissues has been directly linked to many diseases, including Alzheimer's, Parkinson's, amyotrophic lateral sclerosis (ALS), Huntington disease. Recent studies are also linking pathologies such as arthritis and schizophrenia to abnormal trace element concentrations of blood serum in human populations, which are driving questions on elemental distributions in the diseased tissues. In addition, promising new metal-based therapeutics (e.g., anti-cancer and anti-HIV) are driving the need for metal mapping capabilities to better understand the in vivo uptake of the drugs and to determine targeting strategies.

XRF has previously been used for chemical analysis and elemental imaging for metal mapping in biological specimens. High performance synchrotron-based “microXRF” is capable of elemental analysis of biological tissue at cellular and sub-cellular resolution (e.g., microns to 30 nm) with trace-level (e.g., below parts per million (ppm)) sensitivity and quantification. Synchrotron XRF microprobes typically use a monochromator to define a single incident x-ray energy and large synchrotron-specific optics (e.g., Kirkpatrick-Baez mirrors or KB mirrors) to focus the x-rays onto a 0.5-5 μm spot. Example synchrotron-based microXRF studies performed at about 1.6 μm resolution have analyzed intracellular localization of Pt-based anticancer chemotherapeutic compounds in cancerous and non-cancerous cells and the relation of Pt to Zn, providing the insight that Zn-related detoxification was responsible for the development of resistance to chemotherapy. In another example study, synchrotron-based microXRF performed at around 4 μm resolution was used to determine the ration of Co to Cu surrounding failed hip implants, which showed that the failed implants preferentially distributed Co versus non-failed implants, and that analyses of this ratio may inform implant selection. In still another example study, the spatial density of Fe-rich regions in the fingernails of people diagnosed with lung cancer was mapped at about 2 μm resolution.

However, such microXRF systems require access to synchrotron facilities, which are expensive (e.g., each synchrotron facility costs upward to $1B) and are limited in number to only a few centers worldwide. Because of the small number of such facilities with x-ray fluorescence beamlines (e.g., each beamline can cost over $10M), access is immensely competitive. Even if granted, beamtime is often limited to a week or a few days, which is problematic in that it limits the number of samples that can be analyzed, and/or the ability to change the measurement protocol (e.g., improvements to sample preparation and/or sample selection). There are of course additional challenges including logistics of traveling to the synchrotron and the associated costs.

Conventional laboratory-based XRF systems, which had been developed to provide broad access to microspot XRF analysis, are typically based on an electron-bombardment laboratory x-ray source that produces a polychromatic x-ray spectrum, which is then focused to a spot size of about 30-100 μm using polycapillary x-ray optics. In comparison to synchrotron systems, such conventional systems are limited to poorer resolution and have lower sensitivity, which is problematic for elemental analysis of trace concentrations in biological applications.

Certain embodiments described herein provide a system (e.g., an x-ray fluorescence system) comprising a microstructured x-ray source comprising at least one target material (e.g., Au) embedded in a thermally conductive substrate (e.g., diamond), the x-ray source configured to emit x-rays with energies corresponding to one or more characteristic x-ray lines of the at least one target material. The system further comprises an x-ray optic positioned to receive at least a portion of the x-rays from the x-ray source. The x-ray optic comprises an axially symmetric x-ray focusing optic having a depth graded multilayer coating on an inner surface (e.g., with an ellipsoidal profile in a plane along a longitudinal axis of the x-ray optic) configured to substantially reflect (e.g., to have a reflectivity greater than 30%; to have a reflectivity greater than 50%) x-rays having energies in a first predetermined range, to not substantially reflect (e.g., to have a reflectivity less than 10%; to have a reflectivity less than 5%) x-rays in a second predetermined range (e.g., in a range which includes the fluorescence lines of the elements being analyzed), and to focus the reflected x-rays onto a sample (e.g., biological sample; semiconductor sample; geological sample) to be analyzed.

Certain embodiments described herein provide an x-ray optic comprising at least an axially symmetric portion of a tube (e.g., capillary), the portion having an inner surface with a shape (e.g., an ellipsoidal profile in a plane along a longitudinal axis of the x-ray optic) configured for focusing the x-rays from an x-ray source (e.g., with source imaging; with source demagnification; with source magnification). The inner surface of the axially symmetric portion comprises at least one depth graded multilayer coating configured to substantially reflect x-rays having energies in a first range of energies and to not substantially reflect x-rays having energies in a second range of energies that does not overlap the first range of energies.

Certain embodiments described herein provide an x-ray fluorescence system. The system comprises at least one x-ray optic configured to receive at least a portion of a first x-ray beam having a first energy spectrum and to reflect at least some of the x-rays of the portion of the first x-ray beam to form a second x-ray beam. The second x-ray beam has a second energy spectrum. The system further comprises at least one optical element (e.g., mirror) configured to receive at least some of the x-rays of the second x-ray beam, to transmit a third x-ray beam comprising a transmitted portion of the x-rays received from the second x-ray beam, and to reflect a reflected portion of the x-rays received from the second x-ray beam. The third x-ray beam has a third energy spectrum with a reduced intensity, as compared to the second energy spectrum, in a predetermined range of x-ray energies.

Certain embodiments described herein provide a method of performing x-ray fluorescence analysis. The method comprises receiving x-rays having a first energy spectrum and a first spatial distribution and reflecting at least some of the received x-rays. The reflected x-rays have a second energy spectrum and a second spatial distribution. The method further comprises transmitting a first portion of the reflected x-rays to impinge a sample and reflecting a second portion of the reflected x-rays. The first portion has a third energy spectrum that has a reduced intensity, as compared to the second energy spectrum, in a predetermined range of x-ray energies.

Certain embodiments described herein advantageously tailor the energy spectrum of the x-rays incident on the sample to reduce (e.g., remove; cut out) the intensity (e.g., flux) of x-rays in the x-ray fluorescence energy range of interest while preserving (e.g., not substantially affecting) the intensity (e.g., flux) of x-rays at energies higher than the x-ray fluorescence energy range of interest. By reducing the intensity of the incident x-rays in the x-ray fluorescence energy range, certain embodiments reduce the scattered x-ray contribution to the background in the x-ray fluorescence energy range. By preserving the intensity of the incident x-rays at energies above the x-ray fluorescence energy range, certain embodiments maintain (e.g., do not substantially reduce) the x-ray intensity that excites the x-ray fluorescence within the sample. Certain embodiments described herein utilize reflection, rather than absorption, to reduce the intensity of x-rays in the x-ray fluorescence energy range of interest.

Certain embodiments described herein advantageously operate as a “notch filter” in which x-rays within at least one predetermined energy range having a lower bound x-ray energy and an upper bound x-ray energy are substantially prevented from impinging the sample while x-rays outside the at least one predetermined energy range (e.g., at energies above the upper bound x-ray energy; at energies above the upper bound x-ray energy and x-rays below the lower bound x-ray energy) are allowed to propagate to impinge the sample.

Certain embodiments described herein advantageously increase the throughput for x-ray fluorescence analysis by reducing the data acquisition time for performing measurements with sufficient signal-to-noise ratio. For example, the data acquisition time T can be expressed as: T∝B/F², where B is the background contribution and F is the x-ray fluorescence signal. Certain embodiments described herein reduce the background contribution B by about 90% while the x-ray fluorescence signal F is only decreased by about 10%, resulting in a reduction of the data acquisition time T by about 88%.

Certain embodiments described herein are configured to facilitate (e.g., improve) x-ray fluorescence systems configured for trace element mapping (e.g., in biological samples; in semiconductor samples; in geological samples). In certain such embodiments, the bremsstrahlung x-ray beam is refocused using a second paraboloidal optic and the sample is scanned to generate elemental maps of a wide range of elements. Certain embodiments described herein provide more rapid analysis and/or increased sensitivity to the trace elements being analyzed (e.g., by improving the signal-to-noise ratio), while maintaining the desired high spatial resolution (e.g., for semiconductor applications, biomedical research, and other applications). Certain other embodiments described herein provide more rapid analysis and/or increased sensitivity to the trace elements being analyzed (e.g., by improving the signal-to-noise ratio) in applications that do not utilize high spatial resolution (e.g., mineral exploration).

Certain other embodiments are configured to determine the contribution from a first x-ray fluorescence line of a first element (e.g., Hf) from the contribution from a second x-ray fluorescence line of a second element (e.g., Cu) where the first x-ray fluorescence line and the second x-ray fluorescence line have similar (e.g., substantially the same) energies. For example, in a semiconductor processing application, a notch filter can be configured to remove x-rays in an energy range of 9 keV-9.6 keV from an incident x-ray beam, and a sample containing both Cu (e.g., having a K absorption edge at about 9 keV and a Kα fluorescence line at about 8 keV) and Hf (e.g., having an L absorption edge at about 9.6 keV and an Lα fluorescence line at about 8 keV) can be analyzed by (i) measuring a first x-ray fluorescence from the sample with the notch filter preventing x-rays within the energy range from impinging the sample, (ii) measuring a second x-ray fluorescence from the sample without the notch filter preventing x-rays within the energy range from impinging the sample, and (iii) comparing the first x-ray fluorescence and the second x-ray fluorescence. Certain other embodiments described herein are configured to advantageously remove the contributions from diffraction peaks in the measured x-rays. Certain other embodiments described herein are configured to reduce (e.g., prevent; minimize) the flux of x-rays within a selected range of energies from impinging the sample while allowing x-rays outside the selected range of energies to impinge the sample, thereby advantageously reducing the overall x-ray flux impinging the sample (e.g., a sample that is sensitive or susceptible to damage by radiation dosages above a predetermined threshold).

With regard to biological systems, XRF analysis is often complex (e.g., the XRF of different elements are maximized at different energies) and it can be desirable to detect multiple elements simultaneously at the highest sensitivities possible. Certain embodiments described herein produce both strong characteristic x-ray energies related to the x-ray target material and a broad polychromatic x-ray spectrum up to the accelerating voltage of the electron beam of the x-ray source, thus enabling increased excitations.

Certain embodiments described herein provide systems and methods for x-ray fluorescence for chemical analysis and elemental imaging with sub-cellular resolution. As described herein, certain such embodiments can provide advantages even over those provided by a recently developed laboratory microXRF system which incorporates a microstructured x-ray source and a double paraboloidal x-ray optic to achieve resolution less than 10 μm (e.g., 8 μm) and sub-ppm and sub-femtogram (absolute) detection sensitivities. This laboratory-based microXRF system has been applied to a broad range of biological applications by various researchers, including but not limited to: nanoparticle drugs in tumors; trace element dysregulations in diseased calcified tissue such as penile stones, kidney stones, and teeth; genetic modification of crops to improve nutritional uptake (e.g., iron); correlations of elemental anomalous distribution of Zr, I, Cu, and Sr in hair samples with the onset and progression of diabetes, autism, and cancer; Parkinson mouse models and toward the creation of a quantitative hybrid routine using microXRF and inductively coupled plasma mass spectrometry (ICP-MS) techniques. Certain embodiments described herein are configured to advantageously provide imaging of biologically important elements at 1.6 μm resolution with a speed that is three times faster than this system provides at 8 μm resolution. Certain embodiments described herein advantageously expand the use of laboratory microXRF systems for imaging biologically important elements for biomedical applications and speed up the pace of biomedical research that is bottlenecked by low synchrotron access.

Certain embodiments described herein are configured to provide information relevant to metal-binding proteins (e.g., metalloproteins) in the tissue samples. Metalloproteins account for one third of all proteins in the human body, are known to carry out at least one step in almost every biological pathway. The dysregulation of these physiologically important metals is hypothesized to be linked to numerous diseases, including: Menke's and Wilson's diseases, neurodegenerative diseases such as Alzheimer's, Parkinson's, amyotrophic lateral sclerosis (ALS), Huntington disease, autism, and autoimmune diseases such as rheumatoid arthritis, Crohn's, Grave's disease, and infertility. Certain embodiments described herein are configured to provide information relevant to additional elements, previously not found in biological systems, but which are being introduced into such systems, either intentionally (e.g., such as pharmaceutical drugs, which have been moving toward inorganic-based concepts and metal nanoparticles) or unintentionally (e.g., accumulated by environmental exposure, often the result of modern industrial use and pollution), and which can have potential toxic effects. Certain embodiments described herein are configured to provide information relevant to the development of targeted and rational design approaches to metallodrugs (e.g., information relevant to their uptake into tumors, cells, and organelles; information relevant to the removal or detoxification of such drugs; information relevant to the effectiveness of such drugs and/or the development of drug resistance to such drugs).

Certain embodiments described herein provide high spatial resolution imaging information (e.g., relevant to understand the underlying biological functions of physiologically important elements and associated molecules, and biological pathways of therapeutic drugs or toxic elements) with multilength scale resolutions, such as cellular resolution for imaging tissues and organs and sub-cellular resolution for imaging cells, despite the low trace level concentrations of many biologically important elements in biological specimens, due to the small number of metal atoms in the small probed volume. Certain embodiments described herein enable simultaneously imaging multiple elements at sub-cellular resolution and at high sensitivity to provide information relevant to the relationship between elements and corresponding biomolecules (e.g., metalloproteins) and/or textural information (such as K). For example, imaging trace elements along with the distribution of phosphorus, sulfur, and potassium by certain embodiments described herein provides information relevant to spatial correlation with DNA (P), protein (S) and cellular shape (K).

Certain embodiments described herein provide “pre-synchrotron” screening which can inform sample preparation and ensure effective utilization of synchrotron resources, as well as to select samples prior to ultrahigh resolution (e.g., 30 nm-100 nm) XRF studies. Certain embodiments described herein provide analysis of a large number of samples (e.g., used by many biomedical applications) to account for statistical population variance. Certain embodiments described herein provide analysis of samples that cannot be transported other facilities (e.g., synchrotrons) due to the proprietary nature of the samples, the dangerous nature of the samples, or other reasons. Certain embodiments described herein provide high penetration and experimental flexibility in accommodating various specimen sizes and shapes under various conditions (e.g., wet, cryo-preserved, fixed, and/or stained under a range of flexible operating conditions; ambient; cryogenic). Certain embodiments described herein provide non-destructive x-ray fluorescence analysis which can be combined with correlative (e.g., follow-on or follow-up) analysis and/or imaging performed with other techniques, including but not limited to, infrared and Raman spectroscopy/microscopy, molecular mass spectroscopy (e.g., matrix assisted laser desorption/ionization or MALDI), secondary mass spectroscopy x-ray absorption spectroscopy for investigating the chemical state of the elements of interest). Certain embodiments described herein advantageously provide other benefits, including but not limited to: simultaneous detection of many elements within absolute detection limits, and measurements of specimens at or close to their natural state under ambient conditions. Certain embodiments described herein provide much higher spatial resolution than do mass spectroscopy imaging techniques (e.g., laser ablation inductively coupled plasma mass spectrometry or LA-ICP-MS), and orders of magnitude higher sensitivity and lower radiation dose than do electron-based techniques.

Certain embodiments described herein are configured to provide elemental imaging (e.g., information regarding the spatial distributions) of one or more biologically important elements (e.g., in metal-binding proteins) in tissue samples at minor and trace level concentrations (e.g., parts per million; 0.1% or less). FIG. 1 shows examples of biologically important elements that are detectable using hard x-rays in accordance with certain embodiments described herein (see, M. J. Pushie et al., “Elemental and chemically specific x-ray fluorescence imaging of biological systems,” Chemical Reviews 114:17 (2014): 8499-8541). As shown in FIG. 1, biologically important elements can include:

• • physiologically important elements that are known to be essential to life (e.g., Na, Mg, Si, P, S, Cl, K, Ca, V, Mn, Fe, Co, Ni, Cu, Zn, Se, Br, Mo, I). For example, such elements can be components of proteins (e.g., metalloproteins containing Fe, Cu, and/or Zn);
  • pharmacologically active elements that serve as novel therapeutics and diagnostic agents (e.g., Ti, Ga, Zr, Ru, Pd, Ag, Pt, Au, Bi, Gd, Dy). For example, such elements can be components of cancer drugs (e.g., comprising Pt, Au, and/or Ru); and
  • toxic or carcinogenic elements that have widespread distribution due to modern industrial and technological activities (e.g., Al, Cr, As, Sr, Cd, Sn, Sb, Te, Ba, Hg, Tl, Pb, Po, Th, Pa, U, Np, Pu, Am).

FIGS. 2A-2D schematically illustrate various example x-ray optical systems 10 in accordance with certain embodiments described herein. The x-ray optical system 10 (e.g., an x-ray optical filter) of FIG. 2A comprises at least one x-ray optical element 20 (e.g., mirror). In certain embodiments, the at least one x-ray optical element 20 comprises at least one substrate and at least one layer on the at least one substrate. The at least one x-ray optical element 20 is configured to receive a plurality of x-rays (e.g., a first x-ray beam 12) having a first x-ray spectrum with a first intensity as a function of energy in a predetermined solid angle range and to separate the at least some of the received x-rays by multilayer reflection (e.g., reflection that satisfies the Bragg reflection condition from multilayers and/or mosaic crystal layers) or total external reflection into reflected x-rays and non-reflected x-rays. The at least one x-ray optical element 20 is further configured to form a second x-ray beam 32 comprising at least some of the reflected x-rays and/or at least some of the non-reflected x-rays. The second x-ray beam 32 has a second x-ray spectrum with a second intensity as a function of energy in the solid angle range. The second intensity is greater than or equal to 50% of the first intensity across a first continuous energy range at least 3 keV wide, and the second intensity less than or equal to 10% of the first intensity across a second continuous energy range at least 100 eV wide. In certain embodiments, the second intensity is greater than or equal to 50% of the first intensity across a third continuous energy range at least 2 keV wide, the second continuous energy range between the first continuous energy range and the third continuous energy range.

In certain embodiments, as schematically illustrated by FIG. 2B, the x-ray optical system 10 comprises at least one x-ray source 40 configured to generate the first x-ray beam 12 and the at least one x-ray optical element 20 is positioned to receive at least a portion of the x-rays (e.g., at least a portion of the first x-ray beam 12) from the at least one x-ray source 40. As schematically illustrated by FIGS. 2C and 2D, in certain embodiments, at least a portion of the second x-ray beam 32 is configured to irradiate a sample 50 (e.g., a biological sample; a semiconductor sample; a geological sample) and to excite x-ray fluorescence 52 within the sample 50. The x-ray fluorescence 52 is emitted from the sample 50 and comprises x-ray fluorescence lines within the predetermined range of x-ray energies.

In certain embodiments, the system 10 further comprises at least one x-ray detector 60 configured to detect and measure at least a portion of the x-ray fluorescence 52 emitted from the sample 50. For example, the at least one x-ray detector 60 can comprise an energy dispersive detector configured to detect the fluorescence x-rays emitted from the sample (e.g., to generate images indicative of the elemental distribution of the sample). As schematically illustrated by FIG. 2C, the second x-ray beam 32 impinges a first surface 54 of the sample 50 and the at least one x-ray detector 60 is positioned to receive x-ray fluorescence 52 emitted from a second surface 56 of the sample 50 different from the first surface 54 (e.g., the second surface 56 is opposite to the first surface 54). For another example, as schematically illustrated by FIG. 2D, the second x-ray beam 32 impinges the first surface 54 of the sample 50 and the at least one x-ray detector 60 is positioned to receive x-ray fluorescence 52 emitted from the first surface 54 (e.g., a portion of the first surface 54 is impinged by the second x-ray beam 32 and the x-ray fluorescence 52 is received by the at least one x-ray detector 60 from the same portion of the first surface 54 and/or a different portion of the first surface 54). Examples of x-ray detectors 60 compatible with certain embodiments described herein are disclosed by U.S. Pat. Nos. 9,874,531, 9,823,203, 9,719,947, 9,594,036, 9,570,265, 9,543,109, 9,449,781, 9,448,190, and 9,390,881, each of which is incorporated in its entirety by reference herein.

FIG. 3A schematically illustrates an example x-ray optical system 10 in accordance with certain embodiments described herein. The example x-ray optical system 10 of FIG. 3A comprises an x-ray source 40 configured to emit the first x-ray beam 12, the at least one x-ray optical element 20 (e.g., mirror) configured to receive the first x-ray beam 12 and to form and direct the second x-ray beam 32 to impinge the sample 50, and at least one x-ray detector 60 configured to detect (e.g., measure) the fluorescence x-rays emitted from the sample 50. In certain embodiments, the system 10 is integrated with a vacuum system and is configured to provide elemental imaging of samples (e.g., freeze-dried tissue samples; biological samples; semiconductor samples; geological samples). With regard to biological samples, the system 10 of certain embodiments advantageously provides microXRF analysis and imaging with sub-cellular resolution (e.g., in a range of 0.5 μm to 2 μm; 1.5 μm; 1.6 μm; nearly an order of magnitude improvement in resolution over previous systems) and with high sensitivity (e.g., ppm) for the detection of biologically important elements (e.g., Fe, Cu, Zn, P, S) with trace level concentrations.

In certain embodiments, the x-ray source 40 comprises at least one microstructured target 42 having at least one material (e.g., Au) on or embedded in a thermally conductive substrate 44 (e.g., diamond). The at least one material of the at least one microstructured target 42 is configured to emit x-rays (e.g., the first x-ray beam 12) with ultrahigh source brightness upon being bombarded by electrons 46, the first x-ray beam 12 emitted from the x-ray source 40 through at least one window 48. The at least one material of the at least one target 42 is configured to emit x-rays having energies higher than one or more characteristic x-ray fluorescence lines of the sample 50 being analyzed. For example, the characteristic L-lines of Au are slightly above the K-absorption edge of Zn and not far above the K-absorption edges of Fe and Cu, so the L-lines of an Au target material can be more than three times more efficient for production of x-ray fluorescence signals for these example elements. The x-ray source 40 of certain embodiments has as a source size in a range of 5 μm to 15 μm (e.g., 8 μm; 10 μm). Example parameters of the x-ray source 40 include, but are not limited to: an electron beam operating acceleration voltage of 35 kV; an electron power of 30 W; a window 48 comprising beryllium and having a thickness of 50 μm; an electron beam footprint on the target (e.g., full-width-at-half-maximum) of 8 μm (width)×100 μm (length); the substrate 44 comprising diamond with 200 etched trenches (e.g., 4 μm deep, 1 μm thick, and 20 μm wide) extending along the long dimension of the electron beam footprint; trenches filled with the at least one material (e.g., Au) of the at least one target 42; the first x-ray beam 12 having a 5° takeoff angle along the long dimension of the electron beam footprint. Examples of x-ray sources 40 compatible with certain embodiments described herein are disclosed by U.S. Pat. Nos. 9,874,531, 9,823,203, 9,719,947, 9,594,036, 9,570,265, 9,543,109, 9,449,781, 9,448,190, and 9,390,881, each of which is incorporated in its entirety by reference herein.

The example at least one x-ray optical element 20 of FIG. 3A comprises an axially symmetric x-ray focusing optical element 70 (e.g., mirror; mirror lens) and a beam stop 80. The x-ray focusing optical element 70 comprises at least one substrate 72 and at least one layer 74 (e.g., a depth-graded multilayer coating 90) on the at least one substrate 72 and the x-ray focusing optical element 70 is configured to efficiently collect at least some of the x-rays emitted from the x-ray source 40 (e.g., the first x-ray beam 12), the collected x-rays having specific x-ray energies (e.g., the characteristic L-lines of Au). The x-ray focusing optical element 70 is further configured to focus the collected x-rays (e.g., the second x-ray beam 32 consisting essentially of the at least some of the reflected x-rays) onto the sample 50 to be analyzed (e.g., to maximize signal; at least a 13× increase in focused flux of these energies). As schematically illustrated in FIG. 3A, the beam stop 80 is positioned on a longitudinal axis of the x-ray focusing optical element 70 (e.g., at or near an upstream end 76 of the x-ray focusing optical element 70; at or near a downstream end 78 of the x-ray focusing optical element 70; upstream from the x-ray focusing optical element 70; downstream from the x-ray focusing optical element 70). The beam stop 70 is configured to prevent x-rays that are not reflected by the x-ray focusing optical element 70 from impinging the sample 50. Example beam stops 80 compatible with certain embodiments described herein are disclosed by U.S. Pat. Nos. 9,874,531, 9,823,203, 9,719,947, 9,594,036, 9,570,265, 9,543,109, 9,449,781, 9,448,190, and 9,390,881, each of which is incorporated in its entirety by reference herein.

FIG. 3B schematically illustrates an example at least one substrate 72 of the x-ray focusing optical element 70 of FIG. 3A in accordance with certain embodiments described herein. The at least one substrate 72 of certain embodiments comprises a single, unitary element. For example, the at least one substrate 72 can comprise a hollow axially symmetric tube or portion of a tube (e.g., capillary) extending along a longitudinal axis 75 and comprising an inner surface 73 (e.g., mirror surface) that extends fully around the longitudinal axis 75 (e.g., encircles the longitudinal axis 75; extends 360 degrees around the longitudinal axis 75). In certain other embodiments, the at least one substrate 72 comprises at least one portion of a hollow axially symmetric structure (e.g., a portion of an axially symmetric tube) extending along the longitudinal axis 75 with an inner surface that extends only partially around the longitudinal axis 75 (e.g., less than 360 degrees; in a range of 45 degrees to 360 degrees; in a range of 45 degrees to 315 degrees; in a range of 180 degrees to 360 degrees; in a range of 90 degrees to 270 degrees). In certain embodiments, the at least one substrate 72 comprises multiple substrate portions (e.g., 2, 3, 4, 5, 6, or more) separate from one another (e.g., with spaces between the substrate portions) and distributed around the longitudinal axis 75, with the surface 73 of each substrate portion extending at least partially around and along the longitudinal axis 75. For example, the surfaces 73 of the multiple substrate portions can each extend around the longitudinal axis 75 by an angle in a range of 15 degrees to 175 degrees, in a range of 30 degrees to 115 degrees, and/or in a range of 45 degrees to 85 degrees.

In certain embodiments, the surface 73 of the x-ray focusing optical element 70 is configured to focus the x-rays with a 1:1 imaging at the sample 50 of the portion of the x-ray source 40 from which the x-rays are generated (e.g., the source spot on at least one microstructured target 42 from which the x-rays are emitted). In certain other embodiments, the surface 73 of the x-ray focusing optical element 70 is configured to focus the x-rays with magnification (e.g., by at least a factor of 3; by at least a factor of 5; 1:3; 1:5) at the sample 50 of the portion of the x-ray source 40 from which the x-rays are generated (e.g., the source spot on at least one microstructured target 42 from which the x-rays are emitted). In certain other embodiments, the surface 73 of the x-ray focusing optical element 70 is configured to focus the x-rays with demagnification (e.g., by at least a factor of 3; by at least a factor of 5; 3:1; 5:1) at the sample 50 of the portion of the x-ray source 40 from which the x-rays are generated (e.g., the source spot on at least one microstructured target 42 from which the x-rays are emitted). In certain embodiments, as schematically illustrated by FIG. 3B, the surface 73 has an ellipsoidal profile shape (e.g., in a plane along the longitudinal axis) configured for source demagnification (e.g., the surface 73 collects and focuses x-rays from the source spot of the x-ray source 40 to produce a demagnified image of the source spot). For example, the x-ray focusing optical element 70 can be configured for source demagnification by at least a factor of 5 (e.g., 5:1 demagnification; a 5× reduction in spot size), which corresponds to at least a 5:1 ratio of the distance between the source spot and the center of the x-ray focusing optical element 70 to the distance between the center of the x-ray focusing optical element 70 to the focus of the x-ray focusing optical element 70. With a source spot size of 8 μm, the source demagnification of at least a factor of 5 by the x-ray focusing optical element 70 results in a focused spot size equal to or less than 1.6 μm. In certain other embodiments, the source demagnification of the x-ray focusing optical element 70 is at least a factor of 3 (e.g., 3:1 demagnification; a 3× reduction in spot size; a distance of 100 mm between the source spot and the center of the x-ray focusing optical element 70 and a distance of 30 mm between the center of the x-ray focusing optical element 70 and the focus of the x-ray focusing optical element 70), resulting in a focused spot size equal to or less than 2.7 μm for a source spot size of about 8 μm-9 μm. In certain embodiments, the axially symmetric ellipsoidal portion of the reflecting surface 73 of the x-ray focusing optical element 70 has near-minimal surface errors (e.g., surface errors less than 200 nm in size) and/or a focus (e.g., point spread function) of better than 3 μm for a source size of 10 μm (e.g., a focus or point spread function of better than 0.6 μm).

FIG. 3C schematically illustrates an example at least one layer 74 of the x-ray focusing optical element 70 of FIG. 3A in accordance with certain embodiments described herein. The at least one layer 74 comprises at least one depth-graded multilayer 90 (e.g., super-mirror) coated on the surface 73 of the at least one substrate 70 (e.g., fabricated using an atomic layer deposition (ALD) technique; fabricated using sputtering). ALD and sputtering are reasonably mature technologies and are widely used (e.g., in manufacturing advanced integrated circuits; in fabricating multilayers on flat substrate for x-ray monochromators) because of its conformal coating property.

As schematically illustrated in FIG. 3C, the at least one depth-graded multilayer 90 of certain embodiments comprises a plurality of layer pairs 92 (e.g., pairs of layers or bilayers having a high atomic number material and a low atomic number material that alternate in a direction perpendicular to the layers). The thicknesses of the layer pairs differ from one another (e.g., the spacings between sequential high-atomic-number-material layers differ from one another). For example, each layer pair 92 can comprise a first layer 94 comprising a first material and a second layer 96 comprising a second material (e.g., Pt/Si layer pairs; Pt/B₄C layer pairs; Pt/Al₂O₃ layer pairs; W/Si layer pairs; W/B₄C layer pairs; W/Al₂O₃ layer pairs; Mo/Si layer pairs; Mo/B₄C layer pairs; Mo/Al₂O₃ layer pairs; Ni/Si layer pairs; Ni/B₄C layer pairs; Ni/Al₂O₃ layer pairs; Cu/Si layer pairs; Cu/B₄C layer pairs; Cu/Al₂O₃ layer pairs). The thickness (e.g., in a direction substantially perpendicular to the surface 73; d-spacing) of each layer pair 92 is substantially constant along a direction substantially parallel to the surface 73. However, along the normal of the surface 73, layer pairs are configured in sets or groups in which the thicknesses of the layer pairs 72 in each group differ from one another. For example, the thicknesses of the layer pairs 72 of the various groups can increase from a first thickness (e.g., 3 nm) to a second thickness (e.g., 4.5 nm), with the layer groups closer to the surface of the substrate 72 having smaller layer thicknesses than do layer groups farther from the surface of the substrate 72.

In the example depth-graded multilayer 90 of FIG. 3C, the total number of layer pairs 90 is 240, consisting of 6 sets of 40-layer pairs 92. From a first set 98a of layer pairs 92 (e.g., closest to the surface 73) to the last set 98f of layer pairs 92 (e.g., farthest from the surface 73), the thickness of the layer pairs 92 progressively increases (e.g., from 3 nm to 4.5 nm by approximately 0.3 nm=3 Angstroms per set, which is approximately equal to the thickness of two atomic layers). The thickness differences between the sets 98a-98f of layer pairs 92 is limited by the quantized nature of atomic size and does not need to be exact. For example, the depth-graded multilayer 90 can comprise 6 sets of 40 Pt/Al₂O₃ layer pairs or 40 W/Al₂O₃ layer pairs with d spacings ranging from 3 nm to 4.5 nm by approximately 0.3 nm per set. The at least one depth-graded multilayer 90 is substantially different from the multilayers most widely used for monochromators. For example, for monochromators, all the layer pairs have the same thickness as one another. For another example, the typical number of layer pairs used in monochromators (e.g., between 10 and 40) is at least about 3-4 times smaller than the total number of layer pairs 92 of the depth-graded multilayer 90 (e.g., between 100 and 500; between 150 and 400; between 200 and 300).

In certain embodiments, the x-ray focusing optical element 70 is further configured to reduce unwanted background contributions at specific x-ray energies (e.g., by at least a factor of 12) that would otherwise obscure the trace element signals of interest. The main component of this unwanted background contribution is Bremsstrahlung continuum from the laboratory x-ray source 40. Previously, two conventional approaches have been used to minimize the background B_j,k: (i) a crystal or multilayer monochromator to obtain an x-ray excitation beam with a narrow energy bandwidth, but at the cost of substantially reduced flux, and (ii) a spectral filter (e.g., a foil) to absorb a fraction of the “undesirable” x-rays. However, both conventional approaches have major limitations for laboratory microXRF, especially for higher resolution applications in which the focus spot size is smaller than 8 μm. The monochromator approach only provides a limited amount of flux, since only a tiny fraction of the x-ray spectrum is used (e.g., only one x-ray energy, such as the Au Lα energy of 9.713 keV, would be used). Additionally, there are technical challenges associated with the conflicting requirements of: (i) collecting x-rays over a large solid angle to obtain good focused x-ray flux and (ii) the need for highly collimated x-ray beams for use with monochromators, which is made more challenging when collecting x-rays of multiple angular incidences to fulfill requirement (i). As a result, the monochromator approach is almost exclusively performed at synchrotrons and no laboratory microXRF system uses this approach.

FIG. 4A schematically illustrates (i) an example idealized first x-ray spectrum in a predetermined solid angle range of an electron impact x-ray source 40 comprising an Au target 42, the K-edge absorption energies of Fe, Cu, and Zn (at 7.11 keV, 8.98 keV, and 9.66 keV, respectively) and their corresponding Kα characteristic x-ray energies (at 6.4 keV, 8.05 keV, and 8.64 keV, respectively), and (iii) an example idealized second x-ray spectrum in the solid angle range and corresponding to the first x-ray spectrum using absorptive spectral filter comprising a 15-μm thick Cr foil placed in the path of the x-rays from the x-ray source 40. The K-edge absorption energy is the minimum x-ray energy required to ionize the K-shell electrons of the corresponding element and to generate characteristic K-line fluorescence x-rays. The example first x-ray spectrum contains sharp characteristic L-lines of the Au target 42 and continuum Bremsstrahlung radiation (the main component of the background B_j,k). To reduce the x-rays from the x-ray source 40 (e.g., Bremsstrahlung x-rays) having energies equal to the energies of the Fe, Cu, and Zn Kα lines, the spectral absorptive filter comprises a filtering material with an ionization energy lower than the Fe Kα line. As shown in FIG. 4A, the 15-μm thick Cr foil absorptive spectral filter results in the absorption of higher energy x-rays and reduces the background portion of the second x-ray spectrum transmitted through the absorptive spectral filter in a bandwidth of x-rays energies corresponding to the Fe, Cu, and Zn Kα lines. However, the absorptive spectral filter also significantly reduces the useful x-ray energies above the K-edge absorption energies of these elements, leading to an undesirable reduction of the x-ray fluorescence signal F_j,k.

In contrast, FIG. 4B schematically illustrates (i) the example idealized first x-ray spectrum in a predetermined solid angle range and (ii) the K-edge absorption energies of Fe, Cu, and Zn and their corresponding Kα characteristic x-ray energies of FIG. 4A, and (iii) an example idealized second x-ray spectrum in the solid angle range and corresponding to the first x-ray spectrum using an x-ray focusing optical element 70 having a depth-graded multilayer 90 in accordance with certain embodiments described herein. The depth-graded multilayer 90 is configured to serve as a “notch” filter in which the intensity of the second x-ray spectrum (e.g., of the reflected and focused x-rays) is reduced relative to the first x-ray spectrum (e.g., of the x-rays incident to the depth-graded multilayer 90) only in a specific bandwidth, while the rest of the x-ray spectrum is substantially preserved (e.g., the second x-ray spectrum is substantially equal to the first x-ray spectrum). For example, as schematically illustrated by FIG. 4B, the second x-ray spectrum is only reduced for the x-ray energies in the bandwidth of the background that overlap the Fe, Cu, and Zn Kα lines, while the useful higher energy x-rays (e.g., energies above the K-edge absorption energy of Zn) are efficiently preserved, thereby providing optimal fluorescence excitation of the elements of interest. In certain such embodiments, the background B_j,k is reduced (e.g., minimized) while maintaining a high x-ray fluorescence signal F_j,k.

In certain embodiments, the x-ray focusing x-ray optical element 70 (e.g., comprising the at least one substrate 72 and the at least one layer 74 comprising the depth-graded multilayer 90) is configured to provide a near-optimal spectrum for the intended application. For example, applying the Bragg equation (2d·sin θ=λ), x-rays reflected from a location on the depth-graded multilayer 90 have a spectral bandwidth of about 45-50%. The lowest x-ray energy reflected by the depth-graded multilayer 90 is given by the largest incidence angle, which is at the downstream end 78 of the ellipsoidal portion of the x-ray focusing optical element 70 (e.g., the end 78 farthest from the x-ray source 40; see FIG. 3A), and the largest thickness (e.g., d-spacing) (e.g., 4.5 nm).

FIG. 5A shows two example x-ray spectra reflected from the downstream end 78 of the ellipsoidal portion of the x-ray focusing optical element 70 with an incidence angle of 16.7 mrad (0.93 degree) for 4.5 nm and 3 nm d-spacings, respectively. The three fluorescence lines of Fe, Cu, and Zn at 6.4 keV, 8.05 keV, and 8.64 keV, respectively, are within a range of x-ray energies that are not substantially reflected by the ellipsoidal portion of the x-ray focusing optical element 70. The lowest x-ray energy reflected at 16.7 mrad incidence angle by the set 98 of layer pairs 92 having thicknesses (e.g., d-spacing) of 4.5 nm is equal to 8.86 keV, which is about 200 eV higher than the Zn Kα line energy. The x-ray energy reflected at 16.7 mrad incidence angle by the set 98 of layer pairs 92 having thicknesses (e.g., d-spacing) of 3 nm is equal to 13 keV. Therefore, the energy range of the x-rays reflected by the depth-graded multilayer 90 at the downstream end 78 of the x-ray focusing optical element 70 (shown as the shaded region of FIG. 5A) ranges from 8.86 keV to 13 keV, which includes all three intense L-lines of an Au target and also the Bremsstrahlung continuum.

FIG. 5B shows two example x-ray spectra reflected from the upstream end 76 of the ellipsoidal portion of the x-ray focusing optical element 70 with an incidence angle of 12.5 mrad (0.72 degree) for 4.5 nm and 3 nm d-spacings, respectively. The three fluorescence lines of Fe, Cu, and Zn at 6.4 keV, 8.05 keV, and 8.64 keV, respectively, are within a range of x-ray energies that are not substantially reflected by the ellipsoidal portion of the x-ray focusing optical element 70. The x-ray energy range reflected by the depth-graded multilayer 90 at the upstream end 76 of the x-ray focusing optical element 70 (shown as the shaded region of FIG. 5B) ranges from 11.3 keV to 17 keV, which includes two of three intense L-lines of an Au target (11.44 keV and 11.61 keV) and also the Bremsstrahlung continuum. The 9.71 keV L-line of Au is not in this x-ray energy range, but only the downstream half (50%) of the mirror length has sufficiently large incidence angle to satisfy the Bragg reflection condition, so the total collection angle for this line is about 50% of the total collection angle for the two other Au lines. However, the associated loss of the reflected flux of this line is more than offset by the x-ray flux of the Bremsstrahlung continuum over the wide range of 4 keV energy bandwidth. The intensity of the most intense L-lines of Au is about 1000 times higher than the Bremsstrahlung continuum over the energy width of the lines (e.g., about 4 eV), so the x-ray flux of the focused second x-ray beam 32 may contain more up to 50% of the Bremsstrahlung continuum. Note that the lowest energy of the continuum is 8.9 keV, which is higher than the Zn Kα line energy. Therefore, the continuum contributes little to the background B_j,k but contributes significantly to the fluorescence signal F_j,k for Fe, Cu, and Zn.

As shown in FIGS. 5A and 5B, in certain embodiments, the depth-graded multilayer 90 of the x-ray focusing optical element 70 provides spectral “notch” filtering that approximates that shown in FIG. 4B and that reduces the background B_j,k while efficiently reflecting and focusing x-rays of energies that are advantageous (e.g., nearly optimal) for efficiently generating fluorescence signals for elements with ionization absorption edge energies below 8.9 keV. In addition, in certain embodiments, the depth-graded multilayer 90 of the x-ray focusing optical element 70 advantageously increases the solid angle of collection of x-rays from the x-ray source 40 to increase the fluorescence signal F_j,k, as compared to that achieved using conventional focusing optics coated with a single layer of a high atomic number (Z) material.

As shown in the example reflectivity spectra of FIGS. 5A and 5B, the x-ray reflectivity for the x-ray focusing optical element 70 for energies between 5 keV-8.9 keV can be less than 5%. As a result, the background B_j,k resulting from elastically scattering of the incident x-rays over the 5 keV-8.9 keV energy range (e.g., covering the Fe, Cu, and Zn Kα fluorescence lines) can be suppressed by more than a factor of 12 (e.g., by a factor approximately equal to the ratio of the minimum x-ray reflectivity of 60% divided by 5%). This background suppression can improve detection of biologically important elements (e.g., Fe, Co, Cu, Zn) and other elements with characteristic x-rays within that energy range. In addition, in certain embodiments, the 16.7 mrad Bragg (incidence) angle of the depth-graded multilayer 90 is about 2.8× larger than the critical angle of a mirror coated with a single 30-nm thick Au layer for 11.6 keV x-rays (e.g., about 6.2 mrad), resulting in a large solid angle collection of x-rays from the x-ray source 40. Also, in certain embodiments, the second x-ray spectrum reflected and focused by the x-ray focusing optical element 70 includes the Au L-lines and continuum and can be nearly optimal for generating large fluorescence cross sections and signals because these x-rays are slightly above the Zn K-absorption edge and not far above the K-absorption edges of Fe and Cu.

In certain embodiments, the combination of the increased x-ray fluorescence signal and the reduction of background provides a significant gain in the signal-to-noise ratio and the imaging speed for imaging the elements of interest. For example, as described more fully herein, the figure-of-merit (FOM) of certain embodiments is maximized by maximizing the flux of x-rays of energy greater than the K-edge absorption energy to increase the fluorescence signal F_j,k and minimizing the background B_j,k. Besides examples such as Fe, Cu, and Zn (as shown in FIGS. 4A, 4B, 5A, and 5B), many other elements can be advantageously analyzed using certain embodiments described herein, for example, elements having characteristic fluorescence x-rays of energy in a range between 5 keV and 8.9 keV (e.g., the K fluorescence lines of Cr, Mn, Co, and Ni; the L fluorescence lines of various rare earth elements).

Certain embodiments described herein can be characterized by a figure of merit (FOM) that is indicative of the performance of the microXRF system. The minimum detection limit (MDL) using x-ray fluorescence analysis is proportional to 3*F_j,k/sqrt(B_j,k), i.e., MDL˜3 F′_j,k/sqrt(B′_j,k)=3*F_j,k*T/*sqrt(B_j,k*T)=3*sqrt(T)*F_j,k/sqrt(B_j,k), where F′_j,k and F_j,k is the total net counts and count rate (counts/s), respectively, of fluorescence x-rays of an element j for a given characteristic x-ray fluorescence line k integrated over the detector energy resolution band, and the B′_j,k and B_j,k are the total net counts and count rate (counts/s), respectively, of the background underneath the x-ray fluorescence signal (F_j,k), integrated over the same detector energy resolution band. Therefore, the time T required to obtain a given MDL is proportional to B_j,k/F²_j,k, which can be defined as a Figure of Merit (FOM):FOM˜F²_j,k/B_j,k  (1)Certain embodiments described herein are advantageous based at least in part on increasing (e.g., maximizing) the x-ray fluorescence signal (F_j,k) and/or reducing (e.g., minimizing) the background contribution (B_j,k).

The x-ray fluorescence signal (F_j,k) detected by an energy dispersive detector 60 in an x-ray micro-XRF system is approximately given by:F_j,k=F*σ_j,k(E)*N_jΩ*η/4π  (2)where F is the flux of the incident focused second x-ray beam, σ_j,k(E) is the x-ray fluorescence cross section of the element j for the characteristic line k having energy E, N_j is the number of atoms of the element j in the illuminated volume, Ω is the detector solid angle in steradians, and η is a parameter that takes into account losses, including the detector detection efficiency and the attenuation of the fluorescence x-rays from the production point to the detector.

In an evaluation of a microXRF system (e.g., a comparison among different microXRF systems), N_j is the concentration of elements to be measured and should be kept constant. The detector solid angle Ω and the loss parameter η are largely dependent on the detector and physics (self-attenuation) and can be implemented, in principle, in most microXRF systems. Certain embodiments described herein are advantageous based at least in part on increasing (e.g., maximizing) the incident focused x-ray beam flux F and/or increasing (e.g., maximizing) the x-ray fluorescence cross section σ_j,k(E).

With regard to increasing (e.g., maximizing) the incident focused x-ray beam flux F, the incident focused x-ray flux F can be expressed as:F=B*L²*(2NA)²  (3)where B is the product of the x-ray source brightness B at the sample, with brightness B defined as number of x-rays per unit area and per unit solid angle illuminating the sample (and not to be confused with the background contribution B_j,k), L is the focus spot size, and NA is the numerical aperture (which is related to the collection solid angle) of the x-ray focusing optic. The product of L² and (2NA)² is the square of the phase space of the focused x-ray beam.

Certain embodiments described herein are advantageous based at least in part on increasing (e.g., maximizing) the x-ray source brightness B and increasing (e.g., maximizing) the collection solid angle of the x-ray focusing optical element 70 for a given probe spot size L. For example, a high source brightness can be achieved using a microstructured target x-ray source 40 (see, e.g., U.S. Pat. Nos. 9,874,531, 9,823,203, 9,719,947, 9,594,036, 9,570,265, 9,543,109, 9,449,781, 9,448,190, and 9,390,881, each of which are incorporated in its entirety by reference herein) that comprises micron-sized metal targets 42 on or embedded in an anode substrate 44 (e.g., diamond). The brightness B of an electron bombardment x-ray source 40 is directly proportional to the electron power density on the anode, which can be limited by the melting of the anode and therefore the thermal dissipation properties of the anode. Due to the excellent thermal properties of diamond, with a thermal conductivity that is five times that of Au at room temperature, certain embodiments described herein advantageously load the anode with substantially higher electron power densities within a spot (e.g., 8-10 μm spot size) than are used for bulk metal anodes as used in conventional sources. Additional benefits of the microstructured anode include (i) the high temperature gradient between the micron-sized metal targets 42 and the surrounding diamond substrate 44 due to the differential energy deposition rate of the incident electrons, which is proportional to mass density, in the metal material of the target 42 (with higher mass density) versus in the diamond substrate 44 (with lower mass density) and/or (ii) the small size of the microstructure targets 42 have maximal contact between the microstructure target 42 and the diamond substrate 44. The microstructured x-ray source 40 also enables the use of one or more metal materials for the target 42 with x-ray spectral properties optimal for the intended applications (e.g., Au) and/or that otherwise would be impractical to use.

With regard to increasing (e.g., maximizing) the x-ray fluorescence cross section σ_j,k(E), the x-ray fluorescence cross section σ_j,k(E) is equal to the product of the ionization cross section and the fluorescence yield of the characteristic line, which is constant for a given element. The ionization cross section strongly depends on the energy of the incident x-ray beam E and is proportional to (E−E_j,k)⁻³, so the x-ray fluorescence cross section is as well, that is:σ_j,k(E)˜(E−E_j,k)⁻³  (4)where E_j,k is the photon ionization energy of the element j for producing characteristic line k.

Certain embodiments described herein are advantageous based at least in part on selecting the x-ray energy of the excitation beam to increase (e.g., maximize) the quantity (E−E_j,k)⁻³. For example, a microstructured target 42 comprising Au can provide nearly optimal spectra for increasing σ_j,k(E) for many elements, including but not limited to: Fe, Cu, and Zn. FIG. 6 shows a table which lists the x-ray fluorescence cross sections of Fe, Cu, and Zn (used in FIG. 6 as benchmark examples) at four x-ray excitation energies: two major Au L-lines (9.71 keV and 11.44 keV) and two characteristic K-lines of Cu and Mo, target materials widely used in conventional x-ray sources. Other widely used target materials in conventional x-ray sources, such as W and Cr can be unsuitable for the intended applications, since the characteristic L-lines of W and K-lines of Cr are lower than the K-absorption edges of Cu and Zn. As shown in FIG. 6, the two major Au x-ray L-lines have energies above the K-absorption edges of Fe, Cu, and Zn (e.g., three biologically important trace elements) and have large fluorescence cross sections that are three times larger than the fluorescence cross sections of these elements using the characteristic K-line of a Mo target x-ray source. Therefore, an x-ray source with Au microstructured target can provide significantly better spectral properties for generating x-ray fluorescence signals for the three biologically important elements in FIG. 6. These three elements (Fe, Cu, Zn) are discussed herein as benchmark elements because: 1) they exist in very trace quantities and 2) they are of particular interest among various biomedical researchers due to the various pathologies related to their dysregulation and the nature of these trace elements. However, certain embodiments utilizing an Au microstructured x-ray source 40, as described herein, can also be beneficial for many other trace elements of interest, including but not limited to: Mn, Co, Ni, Pt, etc., which each have one or more fluorescence lines in the 5 keV-8.9 keV energy band.

With regard to decreasing the background contribution (B_j,k), the background contribution B_j,k of the x-ray spectrum recorded in a microXRF system arises from two major factors: (i) incident x-rays that are scattered by the sample 50 and detected by the energy dispersive detector 60 (and that have energies within the same energy bandwidth of the corresponding fluorescence signal), and (ii) incomplete charge collection of the energy dispersive detector 60, specified as the peak to background (P/B) ratio. Because widely-used energy dispersive detectors 60 typically have a large P/B ratio (e.g., equal to 20,000), the background contribution B_j,k is dominated by the scattered incident x-rays for a microXRF system. Certain embodiments described herein are advantageous based at least in part on reducing (e.g., minimizing) the incident x-rays within the energy bandwidth of the corresponding fluorescence signal(s) of trace level elements to reduce (e.g., minimize) B_j,k, thereby achieving a large FOM for biologically relevant trace elements. This reduction of B_j,k can be especially advantageous when analyzing trace elements with weak x-ray fluorescence signals (F_j,k).

In certain embodiments, the focusing x-ray optical element 70 comprising the depth-graded multilayer 90 is configured to provide substantial improvement over conventional focusing x-ray optics (e.g., an x-ray optic comprising a coating having a single layer of Pt). For example, the focusing x-ray optical element 70 comprising the depth-graded multilayer 90 can include the following attributes:

• • 1.6 μm resolution (focus spot size) by demagnifying the 8 μm source by a factor of 5;
  • Small decrease of the x-ray fluorescence signals (F_j,k) (e.g., by a factor of 0.49) with the small 1.6 μm focused spot size. The small decrease of F_j,k can be due to the following combination of factors:
    • Increase by a factor of 9 in the solid angle of collection of x-rays from the x-ray source by the multilayer coated focusing x-ray optical element (NA² in expression (3)) due to the Bragg angle reflection of the multilayers being 3 times larger than the critical angle of a single Pt coating of conventional focusing x-ray optical elements;
    • Multilayer reflectivity of 45% (η in expression (2)),
    • Reduction by a factor of 25 in the focus size area (L² in expression (3)), and
    • Increase by a factor of 3 in the x-ray fluorescence cross sections (σ_j,k(E) in expression (2)) due to the Au L-lines with larger fluorescence cross sections of Fe, Cu, Zn.
    • Multiplying these factors together results in a net change of F_j,k by (9*0.45*3/25)=0.49.
  • Decrease (e.g., by more than a factor of 12) in the background count rate B_j,k over the x-ray energy range of 5 keV-8.9 keV for imaging Fe, Cu, and Zn due to reducing (e.g., by more than a factor of 12) the Bremsstrahlung continuum over the energy range in the incident focused x-ray beam.
  • Increase (e.g., by at least a factor of 3=0.49²*12) in the combined net gain in the FOM (see e.g., expression (1)), including the gain from the Au microstructured anode.

In certain embodiments, the net gain in FOM (expression (1)) of a factor of 3 compared to other microXRF systems results from a combination of: a 3× increase of the relative gain in fluorescence cross section of the focused second x-ray beam 32, a 9× increase of the solid angle collection of x-rays from the x-ray source 40, offset by 45% multilayer reflectivity, a 12× reduction of the unwanted background, and a 25× loss of the number of metal atoms due to the reduction of area resulting from the 5× higher resolution (e.g., 5:1 demagnification).

A major challenge for laboratory-based microXRF is to image trace concentrations of the large number of biologically important elements with sufficient sensitivity and at acceptable speeds, and it can be even more challenging to do so at high resolutions. The FOM of a laboratory-based microXRF system can be indicative of the time required to image elements with trace level concentration in biological specimens with sufficient detection sensitivity at a high spatial resolution, an important measurement of performance of a laboratory-based microXRF system. Certain embodiments described herein can provide such images in a shorter amount of time than conventional systems.

In certain embodiments, at large incidence angles of the depth-graded multilayer 90, lower energy x-rays (e.g., up to 4 keV) can be reflected with relatively high efficiency, and these energies can be above the K-absorption edges of P and S. In certain embodiments, a thin film filter (e.g., about 5 mm thick Si) is positioned in the focused x-ray beam path to suppress the unwanted background under the fluorescence lines of P and S. FIG. 7 shows the suppression of unwanted background under the P and S K-line fluorescence using a 5 mm thick Si filter in accordance with certain embodiments described herein. The increase of solid angle of collection of the x-rays from the x-ray source 40 leads to an increase of the flux of the focused x-rays at energies above the K-absorption edge energies of P and S (e.g., by about 5×, which is approximately equal to 9× multiplied by the reflectivity shown in FIGS. 5A and 5B). The combined benefits of the increased solid angle of collection and the background suppression can be offset by a 25× loss of the number of P and S atoms in the probed area/volume due to the 5× higher resolution (e.g., 5:1 demagnification). This net result, combined with their naturally higher concentration, provides sufficient fluorescence signals for imaging.

FIGS. 8A-8D schematically illustrates various other examples of the x-ray optical system 10 in accordance with certain embodiments described herein. As schematically illustrated by FIGS. 8A-8D, the at least one x-ray optical element 20 (e.g., mirror) comprises at least one first x-ray optical element 22 (e.g., mirror) and at least one second x-ray optical element 24 (e.g., mirror). The at least one first x-ray optical element 22 is configured to receive at least a portion of a first x-ray beam 12 having a first energy spectrum and to reflect at least some of the x-rays 26 of the portion of the first x-ray beam 12 (e.g., the x-rays 26 can have an energy spectrum substantially the same as or substantially different from the first energy spectrum). The at least one second x-ray optical element 24 is configured to receive at least some of the x-rays 26 from the at least one first x-ray optical element 22, to transmit a second x-ray beam 32 comprising a transmitted (e.g., non-reflected and non-absorbed) portion of the x-rays 26 received from the at least one first x-ray optical element 22, and to reflect a reflected portion 34 of the x-rays 26 received from the at least one x-ray optical element 22. The second x-ray beam 32 has a second energy spectrum with a reduced intensity, as compared to the first energy spectrum, in a predetermined range of x-ray energies. As schematically illustrated by FIG. 8B, the x-ray optical system 10 can further comprise an x-ray source 40 configured to generate the first x-ray beam 12, and as schematically illustrated by FIGS. 8C and 8D, the x-ray optical system 10 can further comprise at least one x-ray detector 60 configured to detect fluorescence x-rays 52 from a sample 50 (e.g., from the first surface 54 irradiated by the second x-ray beam 32 and/or from a second surface 56 opposite to the first surface 54 irradiated by the second x-ray beam 32).

In certain embodiments, the at least one first x-ray optical element 22 comprises at least one x-ray condenser (e.g., at least one x-ray optical element configured to collect and direct x-rays) having a reflective interface region (e.g., surface) configured to receive at least some of the x-rays of the first x-ray beam 12 and to reflect (e.g., at grazing incidence; total external reflection) at least some of the received x-rays 26 of the first x-ray beam 12. In certain embodiments, the at least one first x-ray optical element 22 is unitary (e.g., a single piece) and is axially symmetric about a longitudinal axis. For example, the at least one first x-ray optical element 22 can comprise a hollow axially symmetric tube or portion of a tube (e.g., capillary) extending along a longitudinal axis and comprising an inner surface (e.g., mirror surface) that extends fully around the longitudinal axis (e.g., encircles the longitudinal axis; extends 360 degrees around the longitudinal axis). In certain other embodiments, the at least one first x-ray optical element 22 comprises at least one portion of a hollow axially symmetric structure (e.g., a portion of an axially symmetric tube) extending along the longitudinal axis with an inner surface that extends only partially around the longitudinal axis (e.g., less than 360 degrees; in a range of 45 degrees to 360 degrees; in a range of 45 degrees to 315 degrees; in a range of 180 degrees to 360 degrees; in a range of 90 degrees to 270 degrees). In certain embodiments, the at least one first x-ray optical element 22 comprises multiple portions (e.g., 2, 3, 4, 5, 6, or more) separate from one another (e.g., with spaces between the portions) and distributed around the longitudinal axis, with the surface of each portion extending at least partially around and along the longitudinal axis. For example, the surfaces of the multiple portions can each extend around the longitudinal axis by an angle in a range of 15 degrees to 175 degrees, in a range of 30 degrees to 115 degrees, and/or in a range of 45 degrees to 85 degrees. In certain other embodiments, the at least one first x-ray optical element 22 comprises a plurality of portions (e.g., a polycapillary lens comprising a plurality of capillary tubes) positioned about a longitudinal axis.

FIG. 9A schematically illustrates a cross-sectional view of an example first x-ray optical element 22 comprising at least one capillary tube 120 in accordance with certain embodiments described herein. The capillary tube 120 (e.g., glass; quartz; silicon) of FIG. 9A is unitary and has an inner surface 122 that is axially symmetric about a longitudinal axis 124 of the capillary tube 120. In certain embodiments, the inner surface 122 comprises at least one metal layer (e.g., Au; Pt; Ir) configured to facilitate reflection of x-rays by the inner surface 122 (e.g., by increasing the critical angle of total external reflection). As schematically illustrated by FIG. 9A, the capillary tube 120 of certain embodiments comprises a paraboloidal-shaped reflective interface region (e.g., inner surface 122). In certain other embodiments, the capillary tube 120 comprises a reflective interface region with a portion that is quadric-shaped (e.g., paraboloidal; ellipsoidal; hyperboloidal) or that approximates a quadric shape. For shapes of the reflective interface region that comprise a focal point (e.g., paraboloidal; ellipsoidal; hyperboloidal), in certain embodiments, at least a portion of the x-ray source 40 is positioned at the focal point, while in certain other embodiments, the x-ray source 40 is displaced from the focal point. The x-ray source 40 can be positioned away from an upstream end 125 of the at least one capillary tube 120 (e.g., by a distance in a range less than 10 cm). Examples of capillary-tube reflective optics 120 compatible with certain embodiments described herein are disclosed by U.S. Pat. Nos. 9,874,531, 9,823,203, 9,594,036, 9,570,265, 9,543,109, 9,449,781, 9,448,190, and 9,390,881, each of which is incorporated in its entirety by reference herein.

As schematically illustrated by FIG. 9A, the at least one first x-ray optical element 22 can further comprise at least one beam stop 80 positioned along a line coincident with the longitudinal axis 124 of the at least one capillary tube 120 (e.g., at or near the upstream end 125 of the at least one capillary tube 120; at or near the downstream end 127 of the at least one capillary tube 120; upstream from the at least one capillary tube 120; downstream from the at least one capillary tube 120). For example, as schematically illustrated by FIG. 9A, a first portion of the first x-ray beam 12 impinges the inner surface 122 of the capillary tube 120 and the x-rays 26 are reflected by the inner surface 122 (e.g., forming a collimated x-ray beam), while a second portion of the first x-ray beam 12 propagates through a center region of the capillary tube 120 and does not impinge the inner surface 122 of the capillary tube 120. The at least one beam stop 80 of certain embodiments comprises at least one material that is opaque to the x-rays (e.g., lead) and the at least one beam stop 80 is configured to prevent (e.g., block) the second portion of the first x-ray beam 12 from contributing to the x-rays 26. In certain embodiments, the x-rays 26 form an x-ray beam having an annular cross-sectional shape in a plane perpendicular to the longitudinal axis 124.

In certain embodiments, the x-rays 26 form an x-ray beam having a beam size (e.g., outer diameter) that is in a range of less than 3 mm (e.g., in a range between 1 mm and 3 mm) at a downstream end 127 of the at least one first x-ray optical element 22. In certain embodiments, the portion of the first x-ray beam 22 received by the at least one first x-ray optical element 22 is divergent (e.g., has a first divergence angle in a range of 5 mrad to 60 mrad) and the x-rays 26 of certain embodiments form a collimated x-ray beam (e.g., having a second divergence angle in a range less than two mrad, less than 1.5 mrad, or less than 1 mrad). FIG. 9B schematically illustrates an example first x-ray energy spectrum of the first x-ray beam 12 (e.g., x-rays from the x-ray source 40) in accordance with certain embodiments described herein. In certain embodiments, the x-rays 26 have an x-ray energy spectrum that is substantially the same as the first x-ray energy spectrum of the first x-ray beam 12, while in certain other embodiments, the x-rays 26 have an x-ray energy spectrum that differs from the first x-ray energy spectrum of the first x-ray beam 12 (e.g., has a high energy cutoff due to the critical angle for total external reflection from the at least one first x-ray optical element 22).

FIG. 10A schematically illustrates an example system 10 in which the at least one second x-ray optical element 24 comprises at least one x-ray reflector 130 (e.g., comprising at least one mosaic crystal layer and/or at least one depth-graded multilayer) in accordance with certain embodiments described herein. FIG. 10B schematically illustrates an example second x-ray energy spectrum of the second x-ray beam 32 (e.g., x-rays transmitted through the at least one x-ray reflector 130) of FIG. 10A in accordance with certain embodiments described herein. FIG. 11A schematically illustrates an example system 10 in which the at least one second optical element 24 comprises a plurality (e.g., two; three or more) x-ray reflectors 130 in accordance with certain embodiments described herein. FIG. 11B schematically illustrates an example second x-ray energy spectrum of the second x-ray beam 32 (e.g., x-rays transmitted through the multiple x-ray reflectors 130) of FIG. 11A in accordance with certain embodiments described herein. FIG. 12A schematically illustrates an example system 10 in which the at least one x-ray reflector 130 comprises at least one grazing incidence mirror in accordance with certain embodiments described herein. FIG. 12B schematically illustrates an example second x-ray energy spectrum of the second x-ray beam 32 (e.g., x-rays transmitted through the at least one x-ray reflector 130) of FIG. 12A in accordance with certain embodiments described herein. The at least one x-ray reflector 130 of FIGS. 10A-10B and 11A-11B can comprise at least one mosaic crystal layer, at least one depth-graded multilayer reflector, and/or at least one grazing incidence mirror, as described herein.

The at least one x-ray reflector 130 is configured to reflect a first portion 132 of the x-rays 26 having energies in at least one predetermined energy range and to transmit a second portion of the x-rays 26 having energies outside the at least one predetermined energy range. As described herein, the transmitted second portion of the x-rays 26 is used as the second x-ray beam 32 which irradiates the sample being analyzed, the second x-ray beam 32 consisting essentially of the at least some of the non-reflected x-rays that are transmitted through the at least one x-ray reflector 130.

For example, the at least one x-ray reflector 130 can comprise at least one mosaic crystal layer on a substrate (e.g., silicon or glass having a thickness in a range of 0.2 millimeter to 1 millimeter). Example materials of the at least one mosaic crystal layer compatible with certain embodiments described herein include but are not limited to, highly oriented pyrolytic graphite (HOPG) or highly aligned pyrolytic graphite (HAPG). The mosaic crystal layer comprises a plurality of crystalline portions (e.g., domains; crystallites) tilted relative to one another with a mosaicity (e.g., range of crystal plane orientations; range of normal directions of the crystal planes). In certain embodiments, the mosaicity is less than three degrees. The x-ray reflector 130 of certain embodiments comprising at least one mosaic crystal layer and a substrate has a thickness in a range of 0.5 mm to 3 mm and the mosaic crystal layer comprises a low atomic number material (e.g., carbon; silicon; quartz) such that absorption of the x-rays 26 by the mosaic crystal layer is lower than a predetermined upper bound (e.g., less than 20%; less than 10%; less than 5%; less than 3%). In certain embodiments, the at least one mosaic crystal layer is planar, while in certain other embodiments, the at least one mosaic crystal layer is curved or bent (e.g., controllably bent to adjust the incident angle at which the x-rays 26 impinge the crystalline portions). In certain embodiments, the at least one mosaic crystal layer is oriented such that a surface of the at least one mosaic crystal layer is in a range of 6 degrees to 20 degrees, in a range of 15 degrees to 40 degrees, in a range of 40 degrees to 50 degrees, or in a range of 40 degrees to 65 degrees, relative to the x-rays 26 (e.g., relative to a collimated x-ray beam comprising the x-rays 26).

At least a first portion 132 of the x-rays 26 impinging the mosaic crystal layer satisfies the Bragg reflection condition for at least some of the crystalline portions of the mosaic crystal layer. The Bragg reflection condition can be expressed as: 2d·sin θ=n·λ, where d is the interplanar spacing between the crystal planes (e.g., carbon layers) of a crystalline portion, θ is the incident angle of the x-ray relative to the crystal planes of the crystalline portion, n is the integer order of the reflection, and λ is the wavelength of the incident x-rays (with the x-ray wavelength related to the x-ray energy by the relation: E=h·c/λ, where E is the energy, h is Planck's constant, and c is the speed of light). The first portion 132 of the x-rays 26 satisfying the Bragg reflection condition for at least some of the crystalline portions of the mosaic crystal layer is reflected by the mosaic crystal layer. The remaining portion of the x-rays 26 that does not satisfy the Bragg reflection condition for any of the crystalline portions of the mosaic crystal layer is not reflected by the mosaic crystal layer and is transmitted through the mosaic crystal layer (e.g., with substantially no attenuation), thereby forming the second x-ray beam 32.

In certain embodiments, due to the slight misalignment among the crystalline portions of the mosaic crystal layer and the small divergence angle of the incident x-rays 26, some of the x-rays 26 within a narrow range of wavelengths will find a crystalline portion for which the Bragg reflection condition is satisfied and will be reflected by the mosaic crystal layer so as to not contribute to the second x-ray beam 32. The mosaic crystal layer can be configured to have a mosaicity and to be oriented relative to the x-rays 26 (e.g., relative to a collimated x-ray beam comprising the x-rays 26) to reflect x-rays having a range of energies with a predetermined central value and predetermined bandwidth (e.g., a range having a lower bound and an upper bound), thereby preventing x-rays within the range (e.g., between the lower bound and the upper bound) from contributing to the second x-ray beam 32.

For another example, the at least one x-ray reflector 130 can comprise at least one depth-graded multilayer reflector, an example of which is schematically illustrated by FIG. 3C. The depth-graded multilayer reflector comprises a substrate (e.g., comprising a low atomic number material, such as silicon, quartz, glass, or aluminum) having a thickness in a range of 0.5 mm to 3 mm or in a range of 0.2 mm to 1 mm and a depth-graded multilayer coating on a surface of the substrate. Absorption of the x-rays 26 by the depth-graded multilayer reflector is lower than a predetermined value (e.g., less than 20%; less than 10%; less than 5%; less than 3%). In certain embodiments, the at least one depth-graded multilayer reflector is oriented such that a surface of the at least one depth-graded multilayer reflector is in a range of 3 degrees to 15 degrees, in a range of 10 degrees to 40 degrees, or in a range of 40 degrees to 50 degrees, relative to the x-rays 26 (e.g., relative to a collimated x-ray beam comprising the x-rays 26).

The at least one depth-graded multilayer of certain embodiments comprises a plurality of layer pairs (e.g., pairs of layers or bilayers having a high atomic number material and a low atomic number material that alternate in a direction perpendicular to the layers). The thicknesses of the layer pairs differ from one another (e.g., the spacings between sequential high-atomic-number-material layers differ from one another). For example, each layer pair can comprise a first layer comprising a first material and a second layer comprising a second material (e.g., Pt/Si layer pairs; Pt/B₄C layer pairs; Pt/Al₂O₃ layer pairs; W/Si layer pairs; W/B₄C layer pairs; W/Al₂O₃ layer pairs; Mo/Si layer pairs; Mo/B₄C layer pairs; Mo/Al₂O₃ layer pairs; Ni/Si layer pairs; Ni/B₄C layer pairs; Ni/Al₂O₃ layer pairs; Cu/Si layer pairs; Cu/B₄C layer pairs; Cu/Al₂O₃ layer pairs). The thickness (e.g., in a direction substantially perpendicular to the substrate surface) of each layer pair is substantially constant along a direction substantially parallel to the surface. However, along the normal of the substrate surface, layer pairs are configured in sets or groups in which the thicknesses of the layer pairs in each group differ from one another. For example, the thicknesses of the layer pairs of the various groups can increase from a first thickness to a second thickness, with the layer groups closer to the substrate surface having smaller layer thicknesses than do layer groups farther from the substrate surface.

At least a first portion 132 of the x-rays 26 impinging the depth-graded multilayer reflector satisfies the Bragg reflection condition (2d·sin θ=n·λ) for at least some of the layers of the depth-graded multilayer coating, where d is the spacing between the high atomic number material layers (e.g., spacing between Pt, W, Mo, Ni, or Cu layers). The first portion 132 of the x-rays 26 satisfying the Bragg reflection condition for at least some of the layers is reflected by the depth-graded multilayer coating. The remaining portion of the x-rays 26 that does not satisfy the Bragg reflection condition for any of the layers of the depth-graded multilayer coating is not reflected by the depth-graded multilayer coating and is transmitted through the depth-graded multilayer coating and the substrate (e.g., with substantially no attenuation), thereby forming the second x-ray beam 32.

In certain embodiments, due to the varying thicknesses of the layers of the depth-graded multilayer coating, the incident x-rays 26 within a narrow range of wavelengths will find a layer spacing for which the Bragg reflection condition is satisfied and will be reflected by the depth-graded multilayer coating so as to not contribute to the second x-ray beam 32. The depth-graded multilayer reflector can be oriented relative to the x-rays 26 (e.g., relative to a collimated x-ray beam comprising the x-rays 26) to reflect x-rays 26 having a range of energies with a predetermined central value and predetermined bandwidth (e.g., a range having a lower bound and an upper bound), thereby preventing x-rays 26 within the range (e.g., between the lower bound and the upper bound) from contributing to the second x-ray beam 32.

As schematically illustrated by FIG. 10B, the second x-ray energy spectrum of the second x-ray beam 32 has a predetermined energy range (e.g., a “notch”) in which the x-ray intensity (e.g., flux) is reduced (e.g., by at least 80%; by at least 90%; by at least 95%) by the at least one x-ray reflector 130 as compared to the x-ray energy spectrum of the first x-ray beam 12 (e.g., schematically illustrated by FIG. 9B). In addition, the second x-ray energy spectrum of the second x-ray beam 32 at energies below a predetermined value (e.g., 4 keV) has a reduced x-ray intensity (e.g., flux) (e.g., by at least 80%; by at least 90%; by at least 95%) as compared to the first x-ray energy spectrum of the first x-ray beam 12 (e.g., schematically illustrated by FIG. 9B).

As schematically illustrated by FIG. 10B, the second x-ray energy spectrum at the upper bound and the lower bound of the predetermined energy range have sharp edges. In contrast to conventional transmission filters used to reduce x-ray flux, certain embodiments described herein provide a sufficiently sharp upper bound edge such that the upper bound can be selected to be between the x-ray absorption edge and the x-ray fluorescence line of the element (e.g., Cu) to be analyzed using the x-ray fluorescence system (e.g., the half-width-at-half-maximum width of the upper bound edge is smaller than the energy difference between the x-ray absorption edge and the x-ray fluorescence line to be analyzed).

FIG. 11A schematically illustrates an example system 10 in which the at least one second x-ray optical element 24 comprises a plurality (e.g., two; three or more) of x-ray reflectors 130 in accordance with certain embodiments described herein. For example, a first x-ray reflector 130a comprising a first substrate and at least one first layer on the first substrate (e.g., at least one mosaic crystal layer and/or at least one depth-graded multilayer) is oriented at a first angle relative to the x-rays 26 (e.g., relative to a collimated x-ray beam comprising the x-rays 26) and a second x-ray reflector 130b comprising a second substrate and at least one second layer on the second substrate (e.g., at least one mosaic crystal layer and/or at least one depth-graded multilayer) is oriented at a second angle, different from the first angle, relative to the x-rays 26 (e.g., relative to a collimated x-ray beam comprising the x-rays 26). The first x-ray reflector 130a is configured to reflect a first portion 132a of the x-rays 26 and the second x-ray reflector 130b is configured to receive the at least some of the non-reflected x-rays from the first x-ray reflector 130a (e.g., the x-rays that are transmitted through the first x-ray reflector 130a) and is configured to reflect a second portion 132b of the x-rays 26, such that the first portion 132a and the second portion 132b do not contribute to the second x-ray beam 32, such that the second x-ray beam 32 consists essentially of the at least some of the non-reflected x-rays from the second x-ray reflector 130b (e.g., the x-rays that are transmitted through the second x-ray reflector 130b).

FIG. 11B schematically illustrates an example second x-ray energy spectrum of the second x-ray beam 32 (e.g., x-rays transmitted through the two x-ray reflectors 130a, 130b) of FIG. 11A in accordance with certain embodiments described herein. For example, the first x-ray reflector 130a can be configured to provide a first “notch” energy range that includes a first x-ray fluorescence line of interest and the second x-ray reflector 130b can be configured to provide a second “notch” energy range that includes a second x-ray fluorescence line of interest (e.g., Hf L_α1 line at 7.9 keV and La L_β1 line at 5 keV; Si K_β1 line at 1.8 keV and Mg K_β1 line at 1.3 keV)). As shown in FIG. 11B, in certain embodiments, the two energy ranges of two “notches” can be separate from one another (e.g., an upper bound of a first energy range from one of the x-ray reflectors 130 is lower than a lower bound of the second energy range from another of the x-ray reflectors 130). In certain other embodiments, the two energy ranges of two “notches” can overlap one another (e.g., the upper bounds of both energy ranges are higher than the lower bounds of both energy ranges), effectively forming one larger energy range over which the background contribution is effectively reduced (e.g., extending from the lower bound of the first energy range to the upper bound of the second energy range).

In the example system of FIGS. 12A-12B, the at least one x-ray reflector 130 comprises at least one grazing incidence mirror in accordance with certain embodiments described herein. For example, the grazing incidence mirror can comprise a substrate (e.g., comprising a low atomic number material, such as silicon, quartz, glass, or aluminum) having a thickness in a range of 0.001 mm to 0.05 mm or in a range of 0.05 mm to 0.2 mm and a coating comprising one or more layers (e.g., comprising a high atomic number material, such as Au, Ir, Pt, W, Cu, or Mo) on a surface of the substrate. Absorption of the x-rays 26 by the grazing incidence mirror is lower than a predetermined value (e.g., less than 20%; less than 10%; less than 5%; less than 3%). In certain embodiments, the grazing incidence mirror is planar, while in certain other embodiments, the grazing incidence mirror is curved or bent. In certain embodiments, the at least one grazing incidence mirror is oriented such that a surface of the grazing incidence mirror is in a range of 1 degree to 10 degrees or in a range of 0.5 degree to 5 degrees, relative to the x-rays 26 (e.g., relative to a collimated x-ray beam comprising the x-rays 26).

At least a first portion 132 of the x-rays 26 impinging the grazing incidence mirror comprises x-rays for which the grazing angle of incidence is below the critical angle for total external reflection by the grazing incidence mirror (e.g., low energy x-rays; x-rays having energies below 1 keV, 3 keV, or 5 keV), and are reflected by the grazing incidence mirror. The remaining portion of the x-rays 26 for which the grazing angle of incidence is above the critical angle for total external reflection (e.g., higher energy x-rays; x-rays having energies above 1 keV, 3 keV, or 5 keV) is not reflected by the grazing incidence mirror and is transmitted through the grazing incident mirror (e.g., with substantially no attenuation), thereby forming the second x-ray beam 32 (e.g., the second x-ray beam 32 consists essentially of the at least some of the non-reflected x-rays from the at least one x-ray reflector 130).

As schematically illustrated by FIG. 12B, the second x-ray energy spectrum of the second x-ray beam 32 transmitted through the grazing incidence mirror at energies below a predetermined “cut-off” value (e.g., 4 keV) has a reduced x-ray intensity (e.g., flux) (e.g., by at least 80%; by at least 90%; by at least 95%) as compared to the first x-ray energy spectrum of the first x-ray beam 12 (e.g., schematically illustrated by FIG. 9B). In certain embodiments, the angle of incidence of the x-rays 26 onto the grazing incidence mirror is adjustable (e.g., relative to the critical angle) so as to adjust the predetermined “cut-off” value of the portion of the x-rays 26.

FIG. 13A schematically illustrates an example system 10 comprising a first x-ray reflector 130 (e.g., a first grazing incidence mirror) and a second x-ray reflector 134 (e.g., a second grazing incidence mirror) in accordance with certain embodiments described herein. The second x-ray reflector 134 is configured to substantially reflect x-rays 136 of the first portion 132 of the x-rays 26 and to not substantially reflect a remaining portion of the first portion 132 of the x-rays 26. FIG. 13B schematically illustrates an example second x-ray energy spectrum of the second x-ray beam 32 and the x-rays 136 reflected from the second x-ray reflector 134 of FIG. 13A in accordance with certain embodiments described herein.

For example, at least some x-rays 136 of the first portion 132 of the x-rays 26 impinging the second x-ray reflector 134 (e.g., second grazing incidence mirror) have a grazing angle of incidence that is below the critical angle for total external reflection by the second x-ray reflector 134 (e.g., low energy x-rays; x-rays having energies below 1 keV, 3 keV, or 5 keV) and are reflected by the second x-ray reflector 134 (e.g., the x-rays 136 are twice reflected, once by the first x-ray reflector 130 and once by the second x-ray reflector 134). The remaining x-rays of the first portion 132 of the x-rays 26 for which the grazing angle of incidence is above the critical angle for total external reflection by the second x-ray reflector 134 (e.g., higher energy x-rays; x-rays having energies above 1 keV, 3 keV, or 5 keV) are not reflected by the second x-ray reflector 134 and are transmitted through the second x-ray reflector 134.

In certain embodiments, as schematically illustrated by FIG. 13A, the first x-ray reflector 130 and the second x-ray reflector 134 can be configured such that the second x-ray beam 32 and the at least some “twice-reflected” x-rays 136 (e.g., of the first portion 132 of the x-rays 26 impinging the second x-ray reflector 134) irradiate the sample 50. In certain embodiments, the x-rays 136 impinge a first region of the sample 50 that is the same as a second region of the sample 50 that is impinged by second x-ray beam 32, while in certain other embodiments, the first region of the sample 50 impinged by the x-rays 136 is different from the second region of the sample 50 impinged by the second x-ray beam 32 (e.g., the first region partially overlaps the second region).

In certain embodiments, the first x-ray reflector 130 is configured to reflect x-rays 132 in a first energy range having a first upper bound (e.g., 4 keV, 5 keV, 6 keV) and the second x-ray reflector 134 is configured to reflect x-rays 136 in a second energy range having a second upper bound (e.g., 2 keV, 3 keV, 4 keV) that is lower than the first upper bound. The energy range between the first upper bound and the second upper bound can have a reduced x-ray intensity (e.g., flux) (e.g., by at least 80%; by at least 90%; by at least 95%) as compared to the x-ray energy spectrum of the first x-ray beam 12 (e.g., schematically illustrated by FIG. 9B). In this way, certain embodiments are configured to perform x-ray fluorescence analysis of high atomic number elements (e.g., using the high energy portion of the x-ray energy spectrum of the second x-ray beam 32 impinging the sample 50) and low atomic number elements (e.g., using the low energy portion of the x-ray energy spectrum of the “twice-reflected” x-rays 136 impinging the sample 50). In certain embodiments, the angle of incidence of the x-rays 26 onto the first x-ray reflector 130 is adjustable and the angle of incidence of the x-rays 132 onto the second x-ray reflector 134 is adjustable (e.g., at slightly different grazing angles relative to the respective critical angles) so as to adjust the portion of the x-rays 26 that does not impinge the sample 50 (e.g., the portion of the x-rays 26 that is not included in either the second x-ray beam 32 or the x-rays 136; so as to cut out an unwanted portion of the low energy spectrum).

FIG. 14 is a flow diagram of an example method 200 of performing x-ray fluorescence analysis in accordance with certain embodiments described herein. In an operational block 210, the method 200 comprises receiving x-rays having a first energy spectrum and a first spatial distribution. In an operational block 220, the method 200 further comprises reflecting at least some of the received x-rays, the reflected x-rays having a second energy spectrum and a second spatial distribution. In an operational block 230, the method 200 further comprises separating the reflected x-rays by multilayer reflection (e.g., reflection that satisfies the Bragg reflection condition from multilayers and/or mosaic crystal layers) and/or total external reflection into a first portion that impinges a sample and a second portion having a predetermined range of x-ray energies. The first portion has a third energy spectrum that has a reduced intensity, as compared to the second energy spectrum, in the predetermined range of x-ray energies. In certain embodiments, at least some of the x-rays of the first portion are configured to excite x-ray fluorescence within the sample, the x-ray fluorescence comprising x-ray fluorescence lines within the predetermined range of x-ray energies. In certain embodiments, the method 200 further comprises reflecting some x-rays of the second portion to impinge the sample.

Conditional language, such as “can,” “could,” “might,” or “may,” unless specifically stated otherwise, or otherwise understood within the context as used, is generally intended to convey that certain embodiments include, while other embodiments do not include, certain features, elements, and/or steps. Thus, such conditional language is not generally intended to imply that features, elements, and/or steps are in any way required for one or more embodiments.

Conjunctive language such as the phrase “at least one of X, Y, and Z,” unless specifically stated otherwise, is to be understood within the context used in general to convey that an item, term, etc. may be either X, Y, or Z. Thus, such conjunctive language is not generally intended to imply that certain embodiments require the presence of at least one of X, at least one of Y, and at least one of Z.

Language of degree, as used herein, such as the terms “approximately,” “about,” “generally,” and “substantially,” represent a value, amount, or characteristic close to the stated value, amount, or characteristic that still performs a desired function or achieves a desired result. For example, the terms “approximately,” “about,” “generally,” and “substantially” may refer to an amount that is within ±10% of, within ±5% of, within ±2% of, within ±1% of, or within ±0.1% of the stated amount. As another example, the terms “generally parallel” and “substantially parallel” refer to a value, amount, or characteristic that departs from exactly parallel by ±10 degrees, by ±5 degrees, by ±2 degrees, by ±1 degree, or by ±0.1 degree, and the terms “generally perpendicular” and “substantially perpendicular” refer to a value, amount, or characteristic that departs from exactly perpendicular by ±10 degrees, by ±5 degrees, by ±2 degrees, by ±1 degree, or by ±0.1 degree.

Various configurations have been described above. Although this invention has been described with reference to these specific configurations, the descriptions are intended to be illustrative of the invention and are not intended to be limiting. Various modifications and applications may occur to those skilled in the art without departing from the true spirit and scope of the invention. Thus, for example, in any method or process disclosed herein, the acts or operations making up the method/process may be performed in any suitable sequence and are not necessarily limited to any particular disclosed sequence. Features or elements from various embodiments and examples discussed above may be combined with one another to produce alternative configurations compatible with embodiments disclosed herein. Various aspects and advantages of the embodiments have been described where appropriate. It is to be understood that not necessarily all such aspects or advantages may be achieved in accordance with any particular embodiment. Thus, for example, it should be recognized that the various embodiments may be carried out in a manner that achieves or optimizes one advantage or group of advantages as taught herein without necessarily achieving other aspects or advantages as may be taught or suggested herein.

Claims

1. An x-ray optical filter comprising at least one x-ray optical mirror, the at least one x-ray optical mirror configured to receive a plurality of x-rays having a first x-ray spectrum with a first intensity as a function of energy in a predetermined solid angle range and to separate at least some of the received x-rays by multilayer reflection or total external reflection into reflected x-rays and non-reflected x-rays and to form an x-ray beam comprising at least some of the reflected x-rays and/or at least some of the non-reflected x-rays, the x-ray beam having a second x-ray spectrum with a second intensity as a function of energy in the solid angle range, the second intensity greater than or equal to 50% of the first intensity across a first continuous energy range at least 3 keV wide, the second intensity less than or equal to 10% of the first intensity across a second continuous energy range at least 100 eV wide.

2. The filter of claim 1, wherein the second intensity is greater than or equal to 50% of the first intensity across a third continuous energy range at least 2 keV wide, the second continuous energy range between the first continuous energy range and the third continuous energy range.

3. The filter of claim 1, wherein the at least one x-ray optical mirror comprises an axially symmetric x-ray focusing optical mirror comprising a substrate and at least one layer on the substrate, the at least one layer comprises a depth-graded multilayer coating, the second x-ray beam consisting essentially of the at least some of the reflected x-rays.

4. The filter of claim 1, wherein the at least one x-ray optical mirror comprises a substrate and at least one layer on the substrate, the at least one layer comprising at least one mosaic crystal layer and/or at least one depth-graded multilayer, the second x-ray beam consisting essentially of the at least some of the non-reflected x-rays.

5. The filter of claim 1, wherein the at least one x-ray optical mirror comprises a first x-ray optical mirror comprising a first substrate and at least one first layer on the first substrate and a second x-ray optical mirror comprising a second substrate and at least one second layer on the second substrate, the second x-ray optical element configured to receive the at least some of the non-reflected x-rays from the first x-ray optical element, the second x-ray beam consisting essentially of the at least some of the non-reflected x-rays from the second x-ray optical element.

6. The filter of claim 1, wherein the at least one x-ray optical mirror comprises at least one grazing incidence mirror, the second x-ray beam consisting essentially of the at least some of the non-reflected x-rays.

7. The filter of claim 1, wherein the at least one x-ray optical mirror comprises a first grazing incidence mirror and a second grazing incidence mirror, the second x-ray beam consisting essentially of the at least some of the non-reflected x-rays from the first grazing incidence mirror, the second x-ray beam and at least a portion of the at least some of the reflected x-rays from the first grazing incidence mirror that is reflected from the second grazing incidence mirror directed to irradiate a sample.

8. A method of performing x-ray fluorescence analysis, the method comprising: receiving x-rays having a first energy spectrum and a first spatial distribution;reflecting at least some of the received x-rays, the reflected x-rays having a second energy spectrum and a second spatial distribution; andseparating the reflected x-rays by multilayer reflection and/or total external reflection into a first portion that impinges a sample and a second portion having a predetermined range of x-ray energies, the first portion having a third energy spectrum that has a reduced intensity, as compared to the second energy spectrum, in the predetermined range of x-ray energies.

9. The method of claim 8, wherein at least some of the x-rays of the first portion are configured to excite x-ray fluorescence within the sample, the x-ray fluorescence comprising x-ray fluorescence lines within the predetermined range of x-ray energies.

10. The method of claim 8, further comprising reflecting some x-rays of the second portion to impinge the sample.

11. An x-ray system comprising: at least one first x-ray optical mirror configured to receive at least a portion of a first x-ray beam having a first energy spectrum and to reflect at least some of the x-rays of the portion of the first x-ray beam to form a second x-ray beam; andat least one second x-ray optical mirror comprising at least one mosaic crystal layer, at least one depth-graded multilayer reflector, and/or at least one grazing incidence mirror, the at least one second x-ray optical mirror configured to receive at least some of the x-rays from the at least one first x-ray optical mirror, to transmit a second x-ray beam comprising a transmitted portion of the x-rays received from the at least one first x-ray optical mirror, and to reflect a reflected portion of the x-rays received from the at least one first x-ray optical mirror, the second x-ray beam having a second energy spectrum with a reduced intensity, as compared to the first energy spectrum, in a predetermined range of x-ray energies.

12. The system of claim 11, wherein at least a portion of the second x-ray beam is configured to irradiate a sample and to excite x-ray fluorescence within the sample, the x-ray fluorescence emitted from the sample and comprising x-ray fluorescence lines within the predetermined range of x-ray energies.

13. The system of claim 11, further comprising an x-ray source configured to generate the first x-ray beam.

14. The system of claim 11, wherein the portion of the first x-ray beam has a first divergence angle in a range of 5 mrad to 60 mrad.

15. The system of claim 14, wherein the x-rays reflected from the at least one first x-ray optical mirror have a second divergence angle in a range less than two mrad.

16. The system of claim 11, wherein the portion of the first x-ray beam is divergent and the x-rays reflected from the at least one first x-ray optical mirror are collimated.

17. The system of claim 11, wherein the x-rays reflected from the at least one first x-ray optical mirror have an energy spectrum that is substantially equal to the first energy spectrum in the predetermined range of x-ray energies.

18. The system of claim 11, wherein the at least one first x-ray optical mirror comprises a paraboloidal-shaped reflective surface.

19. The system of claim 18, further comprising at least one beam stop configured to prevent a second portion of the first x-ray beam that is not reflected by the at least one first x-ray optical mirror from contributing to the second x-ray beam.

20. The system of claim 11, wherein the at least one mosaic crystal layer comprises highly oriented pyrolytic graphite (HOPG) or highly aligned pyrolytic graphite (HAPG), the at least one mosaic crystal layer having a mosaicity in a range of less than three degrees.

21. The system of claim 11, wherein the at least one depth-graded multilayer reflector comprises a substrate and a depth-graded multilayer coating on a surface of the substrate, the substrate comprising at least one material selected from the group consisting of: silicon, quartz, glass, and aluminum.

22. The system of claim 11, wherein the at least one grazing incidence mirror comprises a substrate and a coating on a surface of the substrate, the substrate comprising at least one material selected from the group consisting of: silicon, quartz, glass, and aluminum, the coating comprising at least one material selected from the group consisting of: Au, Ir, Pt, W, Cu, and Mo.

23. The system of claim 11, wherein the at least one grazing incidence mirror comprises a first grazing incidence mirror and a second grazing incidence mirror, the first grazing incidence mirror configured to reflect the reflected portion of the x-rays received from the at least one first x-ray optical element and to transmit the second x-ray beam towards a sample, the second grazing incidence mirror configured to reflect a portion of the reflected portion of the x-rays received from the at least one first x-ray optical element towards the sample.

24. An x-ray system comprising: at least one x-ray source configured to generate x-rays; andat least one x-ray optical element configured to receive and focus at least some of the x-rays from the at least one x-ray source, the at least one x-ray optical element comprising: at least one substrate comprising a surface; andat least one depth-graded multilayer coating on the surface, the at least one depth-graded multilayer coating configured to substantially reflect x-rays having energies in a first energy range and to not substantially reflect x-rays having energies in a second energy range that does not overlap the first energy range.

25. The system of claim 24, wherein the at least one substrate comprises a portion of an axially symmetric tube having a longitudinal axis, the surface comprising an inner surface of the portion.

26. The system of claim 25, wherein the surface has an ellipsoidal cross-sectional profile in a plane along the longitudinal axis.

27. The system of claim 24, wherein at least a portion of the surface has a shape configured for demagnification of a portion of the at least one x-ray source from which the x-rays are generated.

28. The system of claim 24, wherein the depth-graded multilayer coating has a first reflectivity greater than 30% for x-rays in the first energy range and a second reflectivity less than 10% for x-rays in the second energy range.

29. The system of claim 24, wherein the depth-graded multilayer coating comprises a plurality of two-layer pairs, each two-layer pair having a thickness d, wherein at least some of the two-layer pairs have different thicknesses d from one another.

30. The system of claim 29, wherein the two-layer pairs are configured into multiple sets of adjacent two-layer pairs, wherein the two-layer pairs of a first set each have a first thickness d1, the two-layer pairs of a second set each have a second thickness d2 greater than the first thickness d1, the two-layer pairs of a third set each have a third thickness d3 greater than the second thickness d2.

31. The system of claim 24, further comprising a mount configured to hold an object to be analyzed, the at least one x-ray optical element configured to focus the reflected x-rays at the object.

32. The system of claim 24, further comprising at least one x-ray detector subsystem configured to detect fluorescence x-rays from the object, the fluorescence x-rays in the second energy range.