Systems and methods for detecting metal ion concentrations in subjects

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 (IV):

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 any one of claims 1 - 8 , 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 12 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 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.

14. The method of claim 1 , wherein

the first metal ion species is iron or copper, and

the colorimetric indicator is according to Formula (XXII):

wherein,

Q=O, Si(Me) 2 , or C(Me) 2 ,

Y═—OH, morpholine, piperidine, pyrrolidine, or a piperazine derivative,

Z═—CH 3 , —CF 3 , or —COOH, and

A is a metal ion acceptor.

15. The method of claim 14 , wherein

the first metal ion is copper, and

A is 3,6,12,15-tetrathia-9-monoazaheptadecane.

16. A method of detecting copper in a subject, the method comprising:

a) obtaining plasma or urine from the subject;

b) exposing the plasma or urine to a functionalized porous aromatic polymer, wherein the functionalized porous aromatic polymer selectively captures and concentrates copper from the plasma or urine;

c) washing the plasma or urine from the functionalized porous aromatic polymer;

d) exposing the washed functionalized porous aromatic polymer to a solution comprising a colorimetric indicator that extracts the copper from the washed functionalized porous aromatic polymer thereby changing a color of the solution as a function of an amount of the copper in the washed functionalized porous aromatic polymer; and

e) spectroscopically determining, after the exposing d), the concentration of the copper in the subject from the color of the solution by measuring a characteristic absorption wavelength of a complex between copper and the colorimetric indicator.

17. The method of claim 16 , wherein the functionalized porous aromatic polymer is formed from the monomer of Formula (XXIII):

wherein,

X is carbon;

R 1 , R 2 , R 3 and R 4 are independently selected from Formula (XXIV) or (XXV)

wherein,

n is 1, 2 or 3,

m is 1 or 2,

k is 1, 2 or 3, 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.

18. The method of claim 17 , wherein the method further comprises pretreating the biofluid sample prior to the exposing b) with a chelator for iron.

19. The method of claim 18 , wherein the chelator is acetohydroxamic acid, desferoxamine (DFO), or 2,2′-bypyridyl.