1461113833-b36c374f-8d25-4733-8db2-049dbffbf553

1. A labeling reagent comprising an isotopically substituted reagent having a distinct SERS or SERRS spectral signature.
2. The labeling reagent of claim 1 wherein the reagent comprises a deuterated organic dye.
3. The labeling reagent of claim 1 or 2 wherein the organic dye is selected from xanthene dyes, triarylmethane dyes, and azo dyes.
4. The labeling reagent of claim 2 wherein the deuterated organic dye is obtained from a condensation reaction of a deuterated precursor.
5. The labeling reagent of claim 2 wherein the deuterated organic dye is obtained by isotopic exchange of aromatic protons between the organic dye and a deuterated acidic media.
6. A method quantitatively evaluating an analyte comprising the steps of:
labeling a portion of an analyte with an isotopically substituted SERS or SERRS active reagent,
subjecting the analyte to a separating regimen, and detecting the labeled portion with a Raman spectral detector.
7. The method of claim 6 wherein the labeling step comprises the steps of:
mixing a sample containing the analyte of interest with an isotopically edited internal standard of known concentration, and
incubating the mixture with a SERS active reagent to form a bioconjugate.
8. The method of claim 6 or 7 wherein the analyte of interest is a gene fragment.
9. The method of claim 6 or 7 wherein the analyte of interest is a protein or protein based biomarker.
10. The method of claim 7 wherein the detecting step is periodically repeated during the incubating step to quantify the reaction kinetics associated with the analyte colloid binding and exchange reactions.

The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.

1. A non-uniform axial-stiffness ureteral sheath, comprising:
an inner liner defining a longitudinally extending and generally uniform bore;
a non-uniform axial-stiffness outer jacket defining a longitudinally tapered outer surface; and
a reinforcement layer encaencapsulated between the inner liner and the non-uniform axial stiffness outer jacket
wherein at least a portion of the inner liner is so spaced from the non-uniform axial-stiffness outer jacket as to define a region devoid of reinforcement layer structure.
2. The sheath of claim 1, wherein the non-uniform axial-stiffness outer jacket, defines a longitudinally tapered inner surface of the outer jacket.
3. The sheath of claim 1, wherein the non-uniform axial-stiffness outer jacket comprises at least a jacket proximal portion and a jacket distal portion coaxially and tandemly disposed over the reinforcement layer structure, the jacket proximal portion and the jacket distal portion having dissimilar axial-stiffness, wherein the jacket proximal portion and the jacket distal portion are respectively in contact with a radial outer surface of the inner liner.
4. The sheath of claim 1, wherein the non-uniform axial-stiffness outer jacket conforms to a profile of the reinforcement layer.
5. The sheath of claim 4, wherein the non-uniform axial-stiffness outer jacket encases a portion of the reinforcement layer in material forming the outer jacket.
6. The sheath of claim 1, wherein the region is at least partially occupied by a radiopaque element.
7. The sheath of claim 1, wherein the non-uniform axial-stiffness outer jacket defines a jacket distal portion and jacket proximal portion, and along a length of the sheath spanning the jacket distal portion and the jacket proximal portion, there at least a space between the inner liner and the outer jacket that is devoid of reinforcement layer structure.
8. The sheath of claim 1, wherein the reinforcement layer as non-uniform axial-stiffness.
9. The sheath of claim 8, wherein a proximal portion of the reinforcement layer is thicker than a distal portion of the reinforcement layer.
10. The sheath of claim 9, wherein the reinforcement layer comprises a coil of wire, wherein a diameter of the wire in a proximal portion of the reinforcement layer is larger than a diameter of the wire in a distal portion of the reinforcement layer.
11. The sheath of claim 10, wherein the diameter of the tapers from a relatively larger diameter in the proximal portion of the reinforcement layer to a relatively small diameter in the distal portion of the reinforcement layer.
12. The sheath of claim 8, wherein the non-uniform axial-stiffness outer jacket defines a longitudinally tapered inner surface of the outer jacket.
13. The sheath of claim 8, wherein the non-uniform axial-stiffness outer jacket comprises at least a jacket proximal portion and a jacket distal portion coaxially and tandemly disposed over the reinforcement layer structure, the jacket proximal portion and the jacket distal portion having dissimilar axial-stiffness, wherein the jacket proximal portion and the jacket distal portion are respectively in contact with a radial outer surface of the inner liner.
14. The sheath of claim 8, wherein the non-uniform axial-stiffness outer jacket conforms to a profile of the reinforcement layer.
15. The sheath of claim 14, wherein the non-uniform axial-stiffness outer jacket encases a portion of the reinforcement layer in material forming the outer jacket.
16. The sheath of claim 8, wherein at least a portion of the inner liner is so spaced from the non-uniform axial-stiffness outer jacket as to define a region devoid of reinforcement layer structure.
17. The sheath of claim 16, wherein the region is at least partially occupied by a radiopaque element.
18. The sheath of claim 8, wherein the non-uniform axial-stiffness outer jacket defines a jacket distal portion and jacket proximal portion, and along a length of the sheath spanning the jacket distal portion and the jacket proximal portion, there is at least a space between the inner liner and the outer jacket that is devoid of reinforcement layer structure.