Contact lens integrated with a biosensor for the detection of glucose and other components in tears

• US 20100113901A1
• Filed: 10/26/2009
• Published: 05/06/2010
• Est. Priority Date: 10/24/2008
• Status: Active Grant

• Current Assignee: Jin Zhang, William Gerald Hodge
• Original Assignee: Jin Zhang, William Gerald Hodge
• Inventors: Zhang, Jin, Hodge, William Gerald
• Granted Patent: US 8,385,998 B2
• Time in Patent Office: Days
• US Class Current: 600/319
• CPC Class Codes: A61B 5/0017 transmitting optical signals transmission by light H04B10/00
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/1455 using optical sensors, e.g. spectral photometrical oximeters
• CPC Class Codes: B29D 11/00125 Auxiliary operations, e.g. removing oxygen from the mould, conveying moulds from a storage to the production line in an inert atmosphere
• CPC Class Codes: B29D 11/00346 having nanosize structures or features, e.g. fillers
• CPC Class Codes: G02B 1/043 Contact lenses
• CPC Class Codes: G02C 7/04 Contact lenses for the eyes disinfection or sterilisation of contact lenses A61L12/00

Abstract

The present invention provides contact lens with integrated biosensor for the continuous, non-invasive monitoring of physiological glucose by employing biocompatible nanostructure-laden lens materials. These contact lenses can be worn by diabetics who can colorimetrically see changes in their contact lens color or other fluorescence-based properties, giving an indication of tear and blood glucose levels. This invention for the glucose biosensor based on the new disposal contact lens provides a safe, convenient and non-expensive glucose sensing device. The sensing device disclosed herein provides an efficient and noninvasive solution for monitoring blood glucose.

Claims

1. A contact lens with integrated biosensor, comprising:

a) a contact lens having incorporated therein a biosensor for sensing bioanalytes present in tears;

b) the biosensor including a physiologically compatible oxygen permeable substantially transparent and flexible substrate, and physiologically compatible porous nanostructures adhered on said physiologically compatible oxygen permeable and flexible substrate, a physiologically compatible fluorescent assay containing at least one physiologically compatible fluorescent dye encapsulated in said physiologically compatible porous nanostructures, said physiologically compatible fluorescent dye being selected to react or bind with a selected bioanalyte present in tears such that reacting or binding of the bioanalyte with the physiologically compatible fluorescent dye is responsively accompanied by a detectable change in optical properties of the physiologically compatible fluorescent dye indicative of the presence of the bioanalyte in tears when the contact lenses with integrated biosensor is on a person'"'"'s eye; and

c) said biosensor being located in said contact lens at a position off centre in the contact lens such as to not directly obstruct the vision of the person wearing the contact lens.

2. The contact lens with integrated biosensor according to claim 1 wherein said physiologically compatible porous nanostructures are zeolite materials having high surface areas.

3. The contact lens with integrated biosensor according to claim 2 wherein said zeolite materials are aluminosilicate nanocomposite zeolites.

4. The contact lens with integrated biosensor according to claim 1 wherein said physiologically compatible porous nanostructures are silica nanoparticles.

5. The contact lens with integrated biosensor according to claim 1 wherein said physiologically compatible porous nanostructures are selected from the group consisting of silica nanoparticles, nanotubes, nanofilms, and bio-polymer nanostructures including alginate, chitosan nanoparticles (NP), nanofibers, 2-D and 3-D foams with highly nanoporous structures.

6. The contact lens with integrated biosensor according to claim 1 wherein said physiologically compatible oxygen permeable substantially transparent and flexible substrate is PDMS.

7. The contact lens with integrated biosensor according to claim 1 wherein said physiologically compatible oxygen permeable and substantially transparent substrate is selected from the group consisting of silicone acrylates, silicone derivatives including polymethylmethacrylate (PMMA), polydimethylsiloxane, and fluorofoether.

8. The contact lens with integrated biosensor according to claim 1 wherein said detectable change in optical properties of the physiologically compatible fluorescent dye is a color change of that portion of the contact lens into which the biosensor is incorporated, which color change is readily detectable by the person wearing the contact lens.

9. The contact lens with integrated biosensor according to claim 1 wherein said physiologically compatible fluorescent dye is FITC Dextran-TRITC-Con A, and wherein the bioanalyte being detected for is glucose present in tears.

10. The contact lens with integrated biosensor according to claim 1 wherein said physiologically compatible fluorescent dye is selected from the group consisting of FITC Dextran-TRITC-Con A, tetramethyl rhodamine isothiocyanate (TRITC) and 9,10-diphenyl anthracene, and wherein the bioanalyte being detected for is glucose present in tears.

11. The contact lens with integrated biosensor according to claim 1 wherein said physiologically compatible fluorescent dye is Fluorophor 1-Protein (Con A)-Fluorophor 2, and wherein is Fluorophor 1 and Fluorophor 2 have at least 30 nm difference in florescent wavelength.

12. The contact lens with integrated biosensor according to claim 11 wherein pairs of Fluorophor 1 and Fluorophor 2 include rhodamine and fluorescein isothiocyanate (FITC), tetramethyl rhodamine isothiocyanate (TRITC), and fluorescein isothiocyanate (FITC), or tetramethylrhodamine (TAMRA) and FITC (FITC-dextran).

13. The contact lens with integrated biosensor according to claim 1 wherein said physiologically compatible fluorescent dye is selected from the group consisting malachite green (MG) and crystal violet (CV), and wherein the bioanalyte being detected for is Na⁺ and K⁺ present in tears.

14. The contact lens with integrated biosensor according to claim 1 wherein said physiologically compatible fluorescent dye is diaza-18-crown-6 appended with two 5-chloro-8-hydroxyquinolin-7-yl groups, and wherein the bioanalyte being detected for is Mg²⁺ present in tears.

15. The contact lens with integrated biosensor according to claim 1 wherein said physiologically compatible fluorescent dye is 8-hydroxypyrene 1,3,6-trisulfonic acid, and wherein the bioanalyte being detected for is ammonia present in tears.

16. The contact lens with integrated biosensor according to claim 1 wherein said biosensor includes transparent micro/nanospheres having a diameter in a range from about 20 nm to about 200 nm, said transparent micro/nanospheres containing any one or combination of drugs, artificial tears, and cooling agents to reduce symptoms of dry eyes.

17. The contact lens with integrated biosensor according to claim 16 wherein said cooling agents include antipsychotic drugs.

18. The contact lens with integrated biosensor according to claim 16 wherein said artificial tears include solutions of carboxymethyl cellulose, hydroxypropyl methylcellulose, hypromellose, and hydroxypropyl cellulose.

19. The contact lens with integrated biosensor according to claim 16 wherein said transparent micro/nanospheres are made from materials selected from the group consisting of are PLGA, collagen, hydrogels, and alginate.

20. The contact lens with integrated biosensor according to claim 1 wherein said physiologically compatible porous nanostructures have a porosity selected so that the porous nanostructures not only contain one or more fluorescent molecules for the detection of different tear components, but also acts as a reservoir to collect enough amount of tear samples in a short period to decrease a sensor response time and increase the sensitivity of sensor.

21. The contact lens with integrated biosensor according to claim 1 wherein said biosensor includes porous structures embedded therein having a size and porosity to allow update of sample tears by the porous structures and patterned tunnels.

22. The contact lens with integrated biosensor according to claim 21 wherein said porous structures are selected from the group consisting mesoporous silica nanomaterial, hollow tubes and fibers having nano/micro-scale dimensions, and porous polymer spheres having nano/micro-scale dimensions.

23. A method of producing a contact lens with integrated biosensor, comprising the steps of:

a) producing a biosensor by

i) preparing silica nanoparticles with encapsulated at least one fluorescent assay by mixing a silane precursor, TEOS, and said at least one fluorescent assay in absolute alcohol whereby the following reactions take place

hydrolysis;

Si(OEt)₄+H₂O→

(EtO)₃Si—

OH+EtOH 

 

(1)

alcohol condensation;

Si(OEt)₄+(EtO)₃Si—

OH→

(EtO)₃Si—

O—

Si(OEt)₃+EtOH 

 

(2)

H₂O condensation;

(EtO)₃Si—

OH+(EtO)₃Si—

OH→

(EtO)₃Si—

O—

Si(OEt)₃+H₂O 

 

(3)

overall reaction;

Si(OR)₄+2H₂O→

SiO₂+4EtOH 

 

(4)

such that encapsulated organic dye is trapped in polymerized silica nanoparticles by ionic interaction;

ii) assembling dye-loaded silica nanoparticles onto a surface of a physiologically oxygen permeable substrate and adhering them thereto to form one or more layers;

b) fabricating a contact lens and integrating the biosensor into the contact lens with the biosensor being located in said contact lens at a position off centre in the contact lens such as to not directly obstruct the vision of the person wearing the contact lens.

24. The method according to claim 23 wherein step b) of fabricating and integrating the optical sensor into the contact lens is accomplished using any one of photo-polymerization, thermo-polymerization and in situ polymerization.