Flow method and apparatus for screening chemicals using micro x-ray fluorescence
Flow method and apparatus for screening chemicals using micro x-ray fluorescence. The invention includes a method and apparatus for screening a mixture of potential pharmaceutical chemicals for binding to at least one target binder. According to the method, after preparing a solution of potential pharmaceutical chemicals with at least one target binder, the solution is flow-separated into at least two separated components. Each component is exposed to an x-ray excitation beam. Any component that emits a detectable x-ray fluorescence signal is isolated.
1 - 25 . (canceled)
26 . A method for screening chemical binding, comprising:
preparing a solution, the solution comprising at least one chemical and at least one target binder that might combine with the at least one chemical to form a bound complex, the bound complex having a chemical portion and a target binder portion;
flow-separating the solution into at least two separated components;
using a polychromatic x-ray excitation beam to excite atoms of the chemical and of the chemical portion of any bound complex present in any flow separated component in order to produce an x-ray fluorescence signal therefrom;
detecting the x-ray fluorescence signal produced from the excited atoms present in the chemical and chemical portion of any bound complex present in a separated component;
determining from the x-ray fluorescence signal produced from the excited atoms present in the chemical and chemical portion of any bound complex present in a separated component whether or not any separated component comprises a bound complex.
27 . The method of claim 26 , further comprising diverting a chosen flow separated component.
28 . The method of claim 26 , wherein the polychromatic x-ray excitation beam comprises x-rays having an energy greater than 12 KeV.
29 . The method of claim 26 , wherein the polychromatic x-ray excitation beam comprises x-rays having an energy less than 8 KeV.
30 . The method of claim 26 , wherein the polychromatic x-ray excitation beam comprises a greater number of photons having an energy from 12 KeV to 14 KeV than the number of photons having an energy from 9 KeV to 11 KeV.
31 . The method of claim 26 , wherein the polychromatic x-ray excitation beam comprises a greater number of photons having an energy greater than 12 KeV than the number of photons having an energy from 9 KeV to 11 KeV.
32 . The method of claim 26 , wherein the polychromatic x-ray excitation beam is generated using a microfocus x-ray tube.
33 . The method of claim 26 , wherein the polychromatic x-ray excitation beam is focused to a diameter of from about 40 microns to about 100 microns.
34 . The method of claim 26 , wherein the polychromatic x-ray excitation beam comprises an energy spectrum having at least two photon flux maxima peaks.
35 . An apparatus for screening chemical binding, comprising in combination:
(a) a container for a solution of potential pharmaceutical chemicals and at least one target binder;
(b) a flow separator for separating said solution into at least two separated components;
(c) a polychromatic x-ray excitation source for exposing at least one of said flow-separated components to a polychromatic x-ray excitation beam to produce an x-ray fluorescence signal;
(d) an x-ray detector for detecting the x-ray fluorescence signal emitted from a flow-separated component; and
(e) a diverter for diverting a chosen flow-separated component from the remaining solution and any other flow separated component.
36 . The apparatus of claim 35 , wherein said polychromatic x-ray excitation beam comprises x-rays having an energy greater than 12 KeV.
37 . The apparatus of claim 35 , wherein said polychromatic x-ray excitation beam comprises x-rays having an energy less than 8 KeV.
38 . The apparatus of claim 35 , wherein said polychromatic x-ray excitation beam comprises a greater number of photons having an energy from 12 KeV to 14 KeV than the number of photons having an energy from 9 KeV to 11 KeV.
39 . The apparatus of claim 35 , wherein said polychromatic x-ray excitation beam comprises a greater number of photons having an energy greater than 12 KeV than the number of photons having an energy from 9 KeV to 11 KeV.
40 . The apparatus of claim 35 , wherein the energy spectrum of said polychromatic x-ray excitation beam comprises at least two photon flux maxima peaks.
41 . The apparatus of claim 35 , wherein said polychromatic x-ray excitation source comprises a microfocus x-ray tube.
42 . The apparatus of claim 35 , further comprising a focusing optic capable of producing a beam diameter less than about 100 microns.
43 . A method for screening chemical binding, comprising:
preparing a solution, the solution comprising at least one chemical and at least one target binder that might combine with the at least one chemical to form a bound complex, the bound complex having a chemical portion and a target binder portion;
flow-separating the solution into at least two separated components;
using a x-ray excitation beam comprising x-rays having an energy of less than 9 KeV to excite atoms of the chemical and of the chemical portion of any bound complex present in any flow separated component in order to produce an x-ray fluorescence signal therefrom;
detecting the x-ray fluorescence signal produced from the excited atoms present in the chemical and chemical portion of any bound complex present in a separated component;
determining from the x-ray fluorescence signal produced from the excited atoms present in the chemical and chemical portion of any bound complex present in a separated component whether or not any separated component comprises a bound complex.