Multiphase systems for diagnosis of sickle cell disease

Patent metadata

Field	Value
Publication number	US-9678088-B2
Application number	US-201414785980-A
Country	US
Kind code	B2
Filing date	Apr 28, 2014
Priority date	Apr 26, 2013
Publication date	Jun 13, 2017
Grant date	Jun 13, 2017

Abstract

An aqueous multi-phase system for diagnosis of sickle cell disease is described, including two or more phase-separated phases including: a first aqueous phase including a first phase component and having a first density between about 1.025 g/cm 3 and about 1.095 g/cm 3 ; and a second aqueous phase including a second phase component and having a second density between about 1.100 g/cm 3 and about 1.140 g/cm 3 ; wherein the first density is lower than the second density; and each of the first and second phase components include at least one polymer.

First claim

We claim:

1. An aqueous multi-phase system for diagnosis of sickle cell disease, comprising two or more phase-separated phases comprising:
a first aqueous phase comprising a first phase component and having a first density between about 1.025 g/cm 3 and about 1.095 g/cm 3 ; and
a second aqueous phase comprising a second phase component and having a second density between about 1.100 g/cm 3 and about 1.140 g/cm 3 ;
wherein
the first density is lower than the second density; and
each of the first and second phase components comprises at least one polymer.

2. The aqueous multi-phase system of claim 1 , wherein the first density is about 1.025-1.090 g/cm 3 , 1.025-1.080 g/cm 3 , 1.025-1.075 g/cm 3 , 1.025-1.070 g/cm 3 , 1.025-1.065 g/cm 3 , 1.025-1.060 g/cm 3 , 1.025-1.055 g/cm 3 , 1.025-1.050 g/cm 3 , 1.030-1.080 g/cm 3 , 1.030-1.075 g/cm 3 , 1.030-1.070 g/cm 3 , 1.030-1.065 g/cm 3 , 1.030-1.060 g/cm 3 , 1.030-1.055 g/cm 3 , 1.030-1.050 g/cm 3 , 1.040-1.080 g/cm 3 , 1.040-1.075 g/cm 3 , 1.040-1.070 g/cm 3 , 1.040-1.065 g/cm 3 , 1.040-1.060 g/cm 3 , 1.040-1.055 g/cm 3 , or 1.040-1.050 g/cm 3 .

3. The aqueous multi-phase system of claim 1 , wherein the first density is about 1.025-1.030, 1.035-1.050, 1.055-1.070, or 1.075-1.080 g/cm 3 .

4. The aqueous multi-phase system of claim 1 , wherein the second density is about 1.110-1.140 g/cm 3 , 1.110-1.130 g/cm 3 , 1.110-1.125 g/cm 3 , 1.110-1.120 g/cm 3 , 1.115-1.125 g/cm 3 , 1.115-1.120 g/cm 3 , or 1.120-1.125 g/cm 3 .

5. The aqueous multi-phase system of claim 1 , wherein the second density is about 1.115-1.130 g/cm 3 .

6. The aqueous multi-phase system of claim 1 , wherein the first and second densities are about 1.075-1.0798 g/cm 3 and 1.120-1.129 g/cm 3 , respectively.

7. The aqueous multi-phase system of claim 1 , further comprising:
a third aqueous phase comprising a third phase component and having a third density between about 1.075 g/cm 3 and about 1.120 g/cm 3 ;
wherein
the third density is higher than the first density but lower than the second density; and
the third phase component comprises at least one polymer.

8. The aqueous multi-phase system of claim 7 , wherein the third density is about 1.085-1.110 g/cm 3 , 1.090-1.110 g/cm 3 , 1.095-1.110 g/cm 3 , 1.100-1.110 g/cm 3 , 1.105-1.110 g/cm 3 , 1.085-1.105 g/cm 3 , 1.090-1.105 g/cm 3 , 1.095-1.105 g/cm 3 , 1.100-1.105 g/cm 3 , 1.085-1.100 g/cm 3 , 1.090-1.100 g/cm 3 , 1.095-1.100 g/cm 3 , 1.085-1.095 g/cm 3 , or 1.090-1.095 g/cm 3 .

9. The aqueous multi-phase system of claim 7 , wherein the first, third, and second densities are about 1.075-1.083 g/cm 3 , 1.105-1.110 g/cm 3 , and 1.115-1.125 g/cm 3 , respectively.

10. The aqueous multi-phase system of claim 1 , wherein the first, second, and third phase components are each selected from the group consisting of Caboxy-polyacrylamide, Dextran, Ficoll, N,N-dimethyldodecylamine N-oxide, poly(2-ethyl-2-oxazoline), poly(acrylic acid), poly(ethylene glycol), poly(methacrylic acid), poly(vinyl alcohol), polyacrylamide, polyethyleneimine, hydroxyethyl cellulose, poly(2-acrylamido-2-methyl-1-propanesulfonic acid), polyvinylpyrrolidone, Nonyl, polyallylamine, (hydroxypropyl)methyl cellulose, diethylaminoethyl-dextran, nonylphenol polyoxyethylene 20, copolymer, terpolymer, block copolymer, random polymer, linear polymer, branched polymer, crosslinked polymer, and dendrimer system thereof.

11. The aqueous multi-phase system of claim 1 , wherein the first and second components are PEG and Ficoll or PEG and PVA, respectively.

12. The aqueous multi-phase system of claim 1 , wherein the first, third, and second components are PEG, dextran, and PVA, respectively.

13. The aqueous multi-phase system of claim 1 , wherein the concentration of the first phase component in the first phase or the concentration of the second phase component in the second phase is between about 1-40% (w/v).

14. The aqueous multi-phase system of claim 1 , wherein the concentration of the first phase component in the first phase or the concentration of the second phase component in the second phase is about 5%-10%, 10%-15%, or 15%-25% (w/v).

15. The aqueous multi-phase system of claim 7 , wherein the concentration of the third phase component in the third phase is between about 1-40%, 5%-10%, 10%-15%, or 15%-25% (w/v).

16. The aqueous multi-phase system of claim 1 , wherein the aqueous multi-phase system is isotonic.

Assignees

• Harvard College
• Children'S Medical Center Corp
• Brigham & Womens Hospital Inc

Inventors

• Whitesides George M
• Kumar Ashok A
• Hennek Jonathan W
• Lim Caeul
• Moreno Yovany
• Mace Charles R
• Duraisingh Manoj T
• Patton Matthew R
• Lee Si-yi Ryan
• D'Alesio-Spina Gaetana
• Brugnara Carlo
• Stossel Thomas P

Classifications

• G01N15/05

  in blood · CPC title

• G01N2015/0076

  Physics · mapped topic

• G01N33/491

  by separating the blood components (G01N15/05 takes precedence) · CPC title

• G01N33/80 Primary

  involving blood groups or blood types {or red blood cells (white blood cells G01N33/56972)} · CPC title

• G01N2015/0073

  Physics · mapped topic