Fiber optic-based regenerable biosensor

• US 5,176,881 A
• Filed: 09/25/1991
• Issued: 01/05/1993
• Est. Priority Date: 08/11/1989
• Status: Expired due to Fees

• Current Assignee: The University Of Tennessee Research Corporation (University of Tennessee)
• Original Assignee: The University Of Tennessee Research Corporation (University of Tennessee)
• Inventors: Sepaniak, Michael J., Vo-Dinh, Tuan
• Primary Examiner(s): Housel, James C.
• Assistant Examiner(s): Snay, Jeffrey R.
• Application Number:
  US07/765,579
• Time in Patent Office: 468 Days
• Field of Search: 422/68.1, 422/82.05, 422/82.06, 422/82.09, 422/82.08, 422/82, 436/172, 128/633-636, 128/673, 356/39-41
• US Class Current: 422/82
• CPC Class Codes: A61B 5/0071 by measuring fluorescence emission
• CPC Class Codes: A61B 5/0084 for introduction into the body, e.g. by catheters A61B5/1459 takes precedence
• CPC Class Codes: G01N 2021/6434 Optrodes
• CPC Class Codes: G01N 2021/7733 Reservoir, liquid reagent
• CPC Class Codes: G01N 21/7703 using reagent-clad optical fibres or optical waveguides using measurement of total internal reflection or attenuated total reflection G01N21/552; optical fibres or waveguides per se G02B
• CPC Class Codes: G01N 21/8507 Probe photometers, i.e. with optical measuring part dipped into fluid sample
• CPC Class Codes: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings

Abstract

A fiber optic-based regenerable biosensor. The biosensor is particularly suitable for use in microscale work in situ. In one embodiment, the biosensor comprises a reaction chamber disposed adjacent the distal end of a waveguide and adapted to receive therein a quantity of a sample containing an analyte. Leading into the chamber is a plurality of capillary conduits suitable for introducing into the chamber antibodies or other reagents suitable for selective interaction with a predetermined analyte. Following such interaction, the contents of the chamber may be subjected to an incident energy signal for developing fluorescence within the chamber that is detectable via the optical fiber and which is representative of the presence, i.e. concentration, of the selected analyte. Regeneration of the biosensor is accomplished by replacement of the reagents and/or the analyte, or a combination of these, at least in part via one or more of the capillary conduits. The capillary conduits extend from their respective terminal ends that are in fluid communication with the chamber, away from the chamber to respective location(s) remote from the chamber thereby permitting in situ location of the chamber and remote manipulation and/or analysis of the activity with the chamber.

Claims

1. A regenerable microscale biosensor comprising:

a. probe means suitable for disposal in situ of a body site containing a suspect analyte in a fluid, said probe means including;

i. optical fiber means having a first end thereof terminating within said probe means and its opposite end terminating remote from said probe means;

ii. a plurality of capillary conduits having a first of their respective ends terminating within said probe means and their respective opposite ends terminating remote from said probe means;

iii. said first ends of said optical fiber means and said capillary conduits terminating in a substantially common plane;

iv. fritted means porous to said fluid and said suspect analyte defining a cover for said first ends of said optical fiber and said capillary conduits and including an inner wall spaced from said first ends and defining a reaction chamber between said first ends and said cover wherein said first ends of said optical fiber and said capillary conduits are in communication with said reaction chamber; and

v. fluid permeable means covering the first end of at least one of said capillary conduits within said reaction chamber;

b. optical means disposed remotely of said probe means and including

i. a source of radiant energy in communication with that end of said optical fiber remote from said probe means;

ii. means for detecting radiant energy emanating from said reaction chamber through said optical fiber, and

iii. means for converting said emanating radiant energy to a visual indication of the presence of said suspect analyte within said reaction chamber; and

c. means disposed remote from said probe means and communicating with respective ones of the ends of said capillary conduits terminating remote from said probe means for selectively introducing and removing materials into and out of said reaction chamber via said capillary conduits during the in situ disposal of the probe means at the body site, including means for selectively developing vacuum conditions within said reaction chamber for selectively withdrawing the contents of said reactive chamber without withdrawal of said probe means from its in situ body site wherein said reaction chamber is constructed so as to receive further analyte and further materials from a location remote from said reaction chamber without withdrawal of said probe from its in situ body site.

2. The biosensor of claim 1 further including a source of mobile particulates in a fluid medium, wherein said particulates are suitable for transfer into said reaction chamber via one of said capillary conduits.

3. The biosensor of claim 2 wherein said particulates comprise microspheres having an average particle size of less than about 7 μ

m.

4. The biosensor of claim 2 wherein said particulates comprise an inert substance bearing a coating of an antibody.

5. The biosensor of claim 1 further including a means for aspirating said analyte through said reaction chamber comprising:

means for withdrawing said analyte through said reaction chamber from said body site;

means for returning said analyte through said reaction chamber to said body site; and

connecting means having a plurality of connectors for selectively connecting said remote end of at least one of said capillary conduits with at least said means for withdrawing and said means for returning whereby a quantity of said analyte is drawn from said body site, through said fritted means, through said reaction chamber, through said at least one of said conduits and through said connecting means to said means for withdrawing and a reproducible quantity of said analyte is returned from said connecting means through said conduit, through said reaction chamber and to said body site by said means for returning said analyte.