Icagen, Inc.

Caldera Pharmaceuticals, Inc.

Los Alamos National Security, LLC

Xrpro Sciences, Inc.

Jennifer A Berger

Benjamin P Warner

Eva Rachel Birnbaum

Rebecca L E Miller

Sharon M Baldwin

Lori J Peterson

Michael Nathan Harris

Lori J Peterson-Court

Anthony Keiran Burrell

T Mark McCleskey

Andrew Koppisch

Rebecca L Miller

Jeffrey J Stewart

Mark T Mccleskey

Andrew T Koppisch

Michael N Harris

Lori J Petterson

Revecca LE Miller

Rebecca LE Miller

The present invention includes a method and apparatus for measuring the transport of analytes from living, biological cells through a cell barrier, which includes, but is not limited to, steps of providing the living, biological cells loaded with analytes, unloading at least a portion of said analytes from the cells through ion channels, removing unloaded analyte remaining in the cells, and measuring the analytes using x-ray fluorescence, specifically wherein the measurement uses an energy dispersive x-ray fluorescence spectrometer equipped with a microfocus x-ray tube. These steps may be repeated so that multiple measurements can be obtained over a period of time.

Methods for measuring analyte transport across barriers using X-ray fluorescence

The present invention includes a method for analyzing reactions. The method includes the steps of providing a solution of at least one acceptor chemical and at least one donor chemical. The donor chemical is capable of donating a chemical moiety to the acceptor chemical. The solution further includes at least one controller chemical that affects the reaction between the donor chemical and the acceptor chemical. The solution is then incubated so that a portion of the acceptor chemical reacts with the donor chemical to form an acceptor product. Unreacted donor chemical is separated from the acceptor product. The acceptor product or the donor chemical is then measured using X-ray fluorescence. Another aspect of the present invention includes a method for analyzing protein function. The method includes the steps of providing a solution of at least one acceptor chemical and at least one donor chemical. The donor chemical is capable of donating a chemical moiety to the acceptor chemical. The donor chemical includes a functional group selected from ester, anhydride, imide, acyl halide, and amide. The solution is then incubated so that a portion of the acceptor chemical reacts with the donor chemical to form an acceptor product. Unreacted donor chemical is separated from the acceptor product. The acceptor product or the donor chemical is then measured using X-ray fluorescence. Yet another aspect of the present invention includes a method for analyzing protein function. The method includes the steps of providing a solution of at least one acceptor chemical and at least one donor chemical. The solution is then incubated so that a portion of the acceptor chemical reacts with the donor chemical to form an acceptor product. Unreacted donor chemical is separated from the acceptor product. The acceptor product or the donor chemical is then measured using X-ray fluorescence. An additional analytical method is also used to measure either the acceptor product or the donor chemical.

Method and apparatus for measuring protein post-translational modification

X-ray fluorescence (XRF) spectrometry has been used for detecting binding events and measuring binding selectivities between chemicals and receptors. XRF may also be used for estimating the therapeutic index of a chemical. For estimating the binding selectivities of a chemical versus chemical analogs, for measuring post translational modification of proteins, and for drug manufacturing.

Advanced drug development and manufacturing

The present invention includes an apparatus for preparing samples for measurement by x-ray fluorescence spectrometry. The apparatus comprises a plate having one or more holes passing through the plate. The holes are covered by a film on one side of the plate. The holes are less than 500 micrometers across in one dimension where the film covers the holes. The film is translucent to x-rays. The present invention also includes an apparatus for preparing samples for measurement by x-ray fluorescence spectrometry. The apparatus comprises a plate having one or more holes passing through the plate. The holes are covered on one side of the plate by a detachable cover forming a water-tight seal against the plate. The cover is substantially free of the elements osmium, yttrium, iridium, phosphorus, zirconium, platinum, gold, niobium, mercury, thallium, molybdenum, sulfur, lead, bismuth, technetium, ruthenium, chlorine, rhodium, palladium, argon, silver, and thorium. The holes are less than about 500 micrometers across in one dimension where the cover covers the holes. The present invention also includes a method for preparing samples for measurement by x-ray fluorescence spectrometry. The method comprises providing a solution of with less than 10 micromolar solute and a volume of between about 2 microliters and about 2 milliliters. The solution is concentrated and analyzed using x-ray fluorescence spectrometry.

Well plate

The present invention includes a method for analyzing reactions. The method includes the steps of providing a solution of at least one acceptor chemical and at least one donor chemical. The donor chemical is capable of donating a chemical moiety to the acceptor chemical. The solution further includes at least one controller chemical that affects the reaction between the donor chemical and the acceptor chemical. The solution is then incubated so that a portion of the acceptor chemical reacts with the donor chemical form an acceptor product. Unreacted donor chemical is separated from the acceptor product. The acceptor product or the donor chemical is then measured using X-ray fluorescence. Another aspect of the present invention includes a method for analyzing protein function. The method includes the steps of providing a solution of at least one acceptor chemical and at least one donor chemical. The donor chemical is capable of donating a chemical moiety to the acceptor chemical. The donor chemical includes a functional group selected from ester, anhydride, imide, acyl halide, and amide. The solution is then incubated so that a portion of the acceptor chemical reacts with the donor chemical to form an acceptor product. Unreacted donor chemical is separated from the acceptor product. The acceptor product or the donor chemical is then measured using X-ray fluorescence. Yet another aspect of the present invention includes a method for analyzing protein function. The method includes the steps of providing a solution of at least one acceptor chemical and at least one donor chemical. The solution is then incubated so that a portion of the acceptor chemical reacts with the donor chemical to form an acceptor product. Unreacted donor chemical is separated from the acceptor product. The acceptor product or the donor chemical is then measured using X-ray fluorescence. An additional analytical method is also used to measure either the acceptor product or the donor chemical.

The present invention includes a method and apparatus for measuring the transport of an analyte through a cell membrane. One or more cells expressing a plurality of ion channels are provided. These cells are loaded with the analyte so that the cells contain at least 10 picograms of the analyte within a volume defined by the area of an x-ray excitation beam and a depth of five times the 1/e attenuation depth for at least one characteristic x-ray signal of the analyte as attenuated by water. The unloaded analyte is removed and the amount of the analyte in the cells is measured with x-ray fluorescence.

Method for measuring analyte transport across cell membranes using X-ray fluorescence

The present invention comprises a method for measuring the transport of analytes through a cell. The method comprises the steps of providing one or more cells containing at least 10 picograms of an analyte within a volume defined by the area of an x-ray excitation beam and a depth of live times the 1/e attenuation, depth for at least one characteristic x-ray signal of the analyte as attenuated by water. The method further comprises the step of removing at least a of portion of the analyte from the cells. The method also comprises the steps of exciting at least a portion of the analyte that has been removed from the cells with an x-ray beam; and using an x-ray detector to measure x-ray fluorescence.

Methods for measuring analyte transport across barriers using x-ray fluorescence

An apparatus for preparing samples for measurement by x-ray fluorescence spectrometry. A plate has one or more holes passing through the plate. The holes are covered by a film on one side of the plate. The holes are less than 500 micrometers across in one dimension where the film covers the holes. The film is translucent to x-rays.

The present invention includes a method and apparatus for measuring the removal of analyte from a cell. One or more cells are provided, comprising at least 10 picograms of an analyte within a volume defined by the area of an x-ray excitation beam and a depth of a depth of five times the 1/e attenuation depth for at least one characteristic x-ray signal of the analyte as attenuated by water. At least a of portion of the analyte is removed from the cells; and the analyte is measured using x-ray fluorescence.

Growing community of inventors

Los Alamos, NM, United States of America

Jennifer A Berger