Systems and methods for detecting metal ion concentrations in subjects

Patent metadata

Field	Value
Publication number	US-2018024112-A1
Application number	US-201715593117-A
Country	US
Kind code	A1
Filing date	May 11, 2017
Priority date	May 17, 2016
Publication date	Jan 25, 2018
Grant date	—

Abstract

A method of selective detection of a concentration of a metal ion species in a subject is provided in which a biofluid sample is obtained from the subject. The biofluid sample is exposed to a functionalized porous aromatic polymer. The polymer selectively captures and concentrates the metal ion species from the biofluid. Subsequently, the biofluid is washed from the polymer. The polymer is then exposed to a solution comprising a colorimetric indicator that extracts the metal ion species from the washed polymer thereby changing a color of the solution as a function of an amount of the metal ion species in the polymer. The concentration of the metal ion species in the subject is then spectroscopically determined from the color of the solution.

First claim

1 . A method of selective detection of a concentration of a first metal ion species in a subject, the method comprising:
a) obtaining a biofluid sample from the subject; b) exposing the biofluid sample to a functionalized porous aromatic polymer, wherein the functionalized porous aromatic polymer selectively captures and concentrates the first metal ion species from the biofluid sample; c) washing the biofluid sample from the porous aromatic polymer; d) exposing the washed functionalized porous aromatic polymer to a solution comprising a colorimetric indicator that extracts the first metal ion species from the washed functionalized porous aromatic polymer thereby changing a color of the solution as a function of an amount of the first metal ion species in the washed functionalized porous aromatic polymer; and e) spectroscopically determining the concentration of the first metal ion species in the subject from the color of the solution.

2 . The method of claim 1 , wherein the biofluid sample is urine, serum, whole blood, saliva, tears, sweat, breast milk, mucus, blister fluid, or cyst fluid.

3 . The method of claim 1 , wherein
the first metal ion species is copper, and the functionalized porous aromatic polymer is functionalized with an alkyl thioether, a dialkyl thioether, 2,5-dithiahexane, 3,4-dithiahexane, 4,5-dithiahexane, (2-methoxyethyl)(methyl)sulfane, (2-methoxyethyl)(methyl)sulfane, 3-(methylthio)propanoic acid, ethylglycine, N-hydroxy-2-(methyl amino)acetamide, 2-thiopentane, N-hydroxyacetamide, or 2-methylhydrazine-1-carbothioamide.

4 . The method of claim 1 , wherein the first metal ion species is copper and the method further comprises pretreating the biofluid sample prior to the exposing b) with a chelator for a second metal ion species.

5 . The method of claim 4 , wherein the second metal ion species is iron and the chelator is acetohydroxamic acid, desferoxamine (DFO), 2,2′-bypyridyl, 1,10-phenantholine, or ethylenediaminetetraacetic acid (EDTA).

6 . The method of claim 1 , wherein the first metal ion species is copper and the functionalized porous aromatic polymer is formed from the monomer of Formulas (I), (II), (III) or (TV).

wherein,
X is selected from C, Si, and a three-dimensional polycyclic cycloalkyl moiety,
R 1 , R 2 , R 3 and R 4 are independently selected from an alkyl thioether, a dialkyl thioether, 2,5-dithiahexane, 3,4-dithiahexane, 4,5-dithiahexane, (2-methoxyethyl)(methyl)sulfane, (2-methoxyethyl)(methyl)sulfane, 3-(methylthio)propanoic acid, ethylglycine, N-hydroxy-2-(methylamino)acetamide, 2-thiopentane, N-hydroxyacetamide and 2-methylhydrazine-1-carbothioamide, and
the indeces a, b, c and d are members independently selected from the integers 0, 1, 2, 3, and 4, such that when a, b, c, or d is greater than 1, each R 1 , R 2 , R 3 and R 4 , respectively, is independently selected.

7 . The method of claim 1 , wherein
the first metal ion species is copper, and the functionalized porous aromatic polymer is a copolymer formed from a first monomer of Formula (I), (II), (III) or (IV) of claim 6 and a second monomer according to Formula (V):

wherein,
R 5 is a member selected from H, an alkyl thioether, a dialkyl thioether, 2,5-dithiahexane, 3,4-dithiahexane, or 4,5-dithiahexane, (2-methoxyethyl)(methyl)sulfane, (2-methoxyethyl)(methyl)sulfane, 3-(methylthio)propanoic acid, ethylglycine, N-hydroxy-2-(methylamino)acetamide, 2-thiopentane, N-hydroxyacetamide and 2-methylhydrazine-1-carbothioamide,
n is 1, 2, or 3,
e is an integer selected from 0, 1, 2, 3, and 4, such that when e is greater than 1, each R 5 is independently selected, and
said first monomer and said second monomer are covalently bound in said copolymer.

8 . The method of claim 1 , wherein the metal ion species is copper and the functionalized porous aromatic polymer is according to Formula (VI), (VII), (VIII), or (IX):

wherein,
X is selected from C, Si, and a three-dimensional polycyclic cycloalkyl moiety; and
R 1 , R 2 , R 3 and R 4 are each independently selected from Formula (X) or (XI)

wherein,
n is a zero or positive integer,
m is zero or a positive integer,
k is a positive integer,
the indeces a, b, c and d are members independently selected from the integers 0, 1, 2, 3, and 4, such that when a, b, c, or d is greater than 1, each R 1 , R 2 , R 3 and R 4 , respectively, is independently selected.

9 . The method of claim 1 , wherein the first metal ion species is copper and wherein the functionalized porous aromatic polymer is a copolymer formed from a first monomer of Formula (VI), (VII), (VIII) or (IX) of claim 8 and a second monomer of Formula (XII):

wherein,
R 5 is a member selected from H, an alkyl thioether, a dialkyl thioether, 2,5-dithiahexane, 3,4-dithiahexane, 4,5-dithiahexane, (2-methoxyethyl)(methyl)sulfane, (2-methoxyethyl)(methyl)sulfane, 3-(methylthio)propanoic acid, ethylglycine, N-hydroxy-2-(methylamino)acetamide, 2-thiopentane, N-hydroxyacetamide and 2-methylhydrazine-1-carbothioamide,
e is an integer selected from 0, 1, 2, 3, and 4, such that when e is greater than 1, each R 5 is independently selected, and
said first monomer and said second monomer are covalently bound in said copolymer.

10 . The method of claim 1 , wherein
the first metal ion species is copper, and the colorimetric indicator comprises 8-hydroxyquinoline, 2,2′-bipyridine, or 1,10-phenanthroline.

11 . The method of claim 1 , wherein
the first metal ion species is copper, and the spectroscopically determining e) determines whether the subject has Wilson's disease from the color of the solution.

12 . The method of claim 1 , wherein
the first metal ion species is iron, and the functionalized porous aromatic polymer is according to Formula (XIII), (XIV), (XV), or (XVI):

wherein,
X is selected from C, Si, and a three-dimensional polycyclic cycloalkyl moiety;
R 1 , R 2 , R 3 and R 4 are independently selected from Formula (XVII) or (XVIII)

wherein,
the indeces a, b, c and d are members independently selected from the integers 0, 1, 2, 3, and 4, such that when a, b, c, or d is greater than 1, each R 1 , R 2 , R 3 and R 4 , respectively, is independently selected.

13 . The method of claim 1 , wherein
the first metal ion species is iron, and the functionalized porous aromatic polymer is a copolymer formed from a first monomer of Formula (XIII), (XIV), (XV) or (XVI) of claim 11 and a second monomer according to Formula (XIX):

wherein,
R 5 is independently selected from Formula (XX) or (XXI)

e is an integer selected from 0, 1, 2, 3, and 4, such that

Assignees

• Univ California

Inventors

• Chang Christopher J
• Long Jeffrey R
• Lee Sumin
• BARIN Gokhan

Classifications

• G01N31/22

  using chemical indicators (G01N31/02 takes precedence) · CPC title

• G01N33/5306

  Improving reaction conditions, e.g. reduction of non-specific binding, promotion of specific binding · CPC title

• G01N33/52

  Use of compounds or compositions for colorimetric, spectrophotometric or fluorometric investigation, e.g. use of reagent paper {and including single- and multilayer analytical elements (immunological elements G01N33/54386; involving labelled immunochemicals G01N33/58; for haemoglobin or occult blood G01N33/72)} · CPC title

• G01N33/48714 Primary

  for determining substances foreign to the organism, e.g. drugs or heavy metals (drugs by chemical analysis G01N33/94) · CPC title

• G01N33/84

  involving inorganic compounds or pH · CPC title