Fiber Optic Device for Sensing Analytes and Method of Making Same

Abstract

A device for sensing analyte concentration, and in particular glucose concentration, in vivo or in vitro is disclosed. A sensing element is attached to the distal end of an optical conduit, and comprises at least one binding protein adapted to bind with at least one target analyte. The sensing element further comprises at least one reporter group that undergoes a luminescence change with changing analyte concentrations. Optionally, the optical conduit and sensing element may be housed within a cannulated bevel.

1 .- 71 . (canceled) 
     
     
         72 . A device for sensing a target analyte in a sample comprising:
 (a) an optical fiber having a proximal end and a distal end;   (b) an optical system at the proximal end of the optical fiber comprising at least one electromagnetic energy emitter and at least one electromagnetic energy detector; and   (c) a sensing element attached to the distal end of the optical fiber and in optical connectivity with the optical fiber, the sensing element comprising (i) at least one periplasmic binding protein (PBP) capable of specifically binding with at least one target analyte and at least one reporter group associated with the PBP and (ii) a polymeric matrix that is covalently attached to said distal end of the optical fiber, wherein the PBP and reporter group are entrapped within or attached to the polymeric matrix, wherein the matrix permits the PBP to retain conformational mobility, and wherein the matrix is adapted to transduce a luminescence change of the reporter group upon specific binding of the PBP to the target analyte.   
     
     
         73 . The device of  claim 72 , further comprising a tip that houses and protects the optical fiber and the sensing element within the tip, wherein the tip is selected from the group consisting of a needle and a catheter. 
     
     
         74 . The device of  claim 72 , wherein the sensing element is further adapted to be inserted into or through the skin of a patient. 
     
     
         75 . The device of  claim 72 , wherein the PBP is glucose-galactose binding protein (GGBP). 
     
     
         76 . The device of  claim 72 , wherein the target analyte is glucose. 
     
     
         77 . The device of  claim 72 , further comprising one or more connectors. 
     
     
         78 . The device of  claim 77 , wherein the sensing element is attached to the proximal end of the optical fiber through said one or more connectors. 
     
     
         79 . The device of  claim 72 , wherein said optical fiber comprises silica. 
     
     
         80 . The device of  claim 72 , wherein the electromagnetic energy emitter is selected from the group consisting of an arc lamp, a light emitting diode, and a laser diode. 
     
     
         81 . The device of  claim 72 , wherein the electromagnetic energy detector is a photodiode, photomultiplier tube, or charge coupled device and the electromagnetic energy detector is adapted to detect energy emitted by said reporter group substantially continuously or periodically. 
     
     
         82 . The device of  claim 72 , wherein said optical system further comprises optical elements selected from the group consisting of optical filters, dichroic components, holographic components and combinations thereof, wherein the optical elements are adapted to distinguish multiple wavelengths. 
     
     
         83 . The device of  claim 72 , wherein said optical system further comprises electrical or optoelectronic elements for modulation of the signal from the electromagnetic energy emitter. 
     
     
         84 . The device of  claim 72 , wherein said optical system further comprises electrical or optoelectronic elements for modulation of the luminescence signal received by the electromagnetic energy detector. 
     
     
         85 . The device of  claim 72 , wherein the optical system is adapted to measure at least one quality of the luminescence signal, with the quality selected from the group consisting of intensity, wavelength, lifetime and polarization of the luminescence signal. 
     
     
         86 . The device of  claim 72 , wherein the sensing element comprises at least one reference group associated with the PBP. 
     
     
         87 . The device of  claim 86 , wherein the at least one reporter group and the at least one reference group are excited at the same or different wavelengths. 
     
     
         88 . The device of  claim 86 , wherein the luminescence of the at least one reporter group and the luminescence of the at least one reference group are detected at the same or different wavelengths. 
     
     
         89 . The device of  claim 72 , wherein the reporter group comprises a pair of organic dyes adapted so that the energy transfer efficiency between the pair changes upon analyte binding. 
     
     
         90 . The device of  claim 72 , wherein the reporter group comprises a pair of fusion proteins adapted so that the energy transfer efficiency between the pair changes upon analyte binding. 
     
     
         91 . The device of  claim 72 , wherein the reporter group comprises an organic dye and a protein chosen so that the energy transfer efficiency between the organic dye and the protein changes upon analyte binding.