1. A cryosurgical probe assembly, comprising:
a) a gas delivery assembly, comprising a stem and a fluid conduit subassembly bonded to said stem, said fluid conduit subassembly for delivering and returning cooling fluid used for cryogenic cooling, said fluid conduit subassembly, comprising:
i. a shaft for providing a heat exchange surface for cryogenic ablation;
ii. a housing securely connected to said shaft; and,
iii. an insulation element slideably engaged with an inner surface of said shaft and slideably engaged with said stem;
b) an adjustable sliding apparatus, comprising:
i. a slider assembly securely attached to said insulation element for slideably guiding said insulation element along said shaft; and,
ii. a button assembly operatively connected to said slider assembly for allowing a user to actuate said slider assembly to provide a desired adjustment of said insulation element relative to said shaft; and,
c) a handle assembly positioned about said housing.
2. The cryosurgical probe assembly of claim 1, wherein said insulation element comprises a vacuum tube.
3. The cryosurgical probe assembly of claim 1, wherein said cryosurgical probe assembly is detachable.
4. The cryosurgical probe system of claim 1, wherein said handle comprises a guideway formed therein for providing access to said button assembly.
5. The cryosurgical probe system of claim 1, wherein said button assembly can be locked into position to prevent unintentional movement.
6. The cryosurgical probe assembly of claim 1, wherein said cryosurgical probe assembly is a disposable probe assembly of a detachable cryosurgical probe, said disposable probe assembly, further comprising:
a) a finger lock element, comprising:
1. a distal finger lock element section having a threaded inner surface for engagement with a threaded outer surface of said stem; and,
2. a plurality of radially spaced fingers extending proximally from said distal finger lock element section, each finger having a) a ramped surface for operatively engaging an associated ramp section on said stem during use; and, b) a female lip at a proximal end thereof.
7. The cryosurgical probe system of claim 1, wherein said gas delivery system includes a Joule-Thomson (J-T) tube bonded to said stem.
8. The cryosurgical probe system of claim 1, wherein said fluid conduit subassembly, comprises:
a) a Joule-Thomson (J-T) tube bonded to said stem, said J-T tube for receiving cooling fluid from a reusable probe assembly;
b) a safety washer positioned within a front end of an elongated central opening of said distal handle section of said handle assembly;
c) a shaft secured to said safety washer within an opening of said safety washer and within said elongated central opening, said shaft extending beyond a distal handle section of said handle assembly to provide a cooling surface for cryogenic cooling;
d) said vacuum tube integrally connected to an inner surface of said shaft; and,
e) a high pressure seal comprising a high pressure o-ring positioned about a proximal end section of said stem, for sealing cooperation with an inner surface of a manifold assembly of the reusable probe assembly.
9. The cryosurgical probe system of claim 1, wherein said fluid conduit subassembly, comprises:
a) a Joule-Thomson (J-T) tube bonded to said stem, said J-T tube for receiving cooling fluid from a reusable probe assembly;
b) a safety washer assembly positioned within a front end of an elongated central opening of a distal handle section of said handle assembly, said safety washer assembly including a first o-ring,
i. said shaft being secured to said safety washer assembly within an opening of said safety washer and within said elongated central opening, said shaft extending beyond said distal handle section to provide a cooling surface for cryogenic cooling,
ii. said first o-ring for sealing said shaft to said vacuum tube; and,
c) a second o-ring positioned within a front end of said stem, for sealing cooperation with said vacuum tube.
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 monoclonal antibody that selectively binds to one of the following:
(a) hemoglobin variant HbD and glycated HbD, wherein the antibody binds to a HbD minimal epitope 121QFTPP125 (SEQ ID NO:8) or 119GKQFTPP125 (SEQ ID NO:46); or
(b) hemoglobin variant HbE and glycated HbE, wherein the antibody binds to a HbE minimal epitope 22EVGGK26 (SEQ ID NO:6) or 21DEVGGK26 (SEQ ID NO:7).
2. A method for individually detecting a plurality of hemoglobin-containing analytes comprising HbA1c and a hemoglobin variant, if present, in a single sample of blood cell lysate, said method comprising:
(a) incubating said sample with a population of beads in a common mixture, said population comprising a subpopulation to detect HbA1c and one or more further subpopulations, each of which detects a hemoglobin variant, wherein:
(i) each bead of said subpopulation to detect HbA1c has bonded thereto a classifier dye and each bead of said one or more subpopulations to detect a hemoglobin variant has bonded thereto a classifier dye where the classifier dyes are selected such that the classifier dyes, and thereby said subpopulations, are differentiable from each other by fluorescent emissions emitted by said classifier dyes upon excitation, and
(ii) each bead of said subpopulation to detect HbA1c further has bonded thereto an antibody having selective binding affinity towards HbA1c and each bead of said one or more subpopulations to detect a hemoglobin variant has bonded thereto a monoclonal antibody that has selective binding affinity towards the variant and the glycated form of the variant to cause each analyte to bind to the different bead subpopulation through the antibody bonded to said subpopulations, wherein:
one subpopulation of the one or more further subpopulations detects HbD, if present in the sample, and has bonded thereto a monoclonal antibody having selective binding affinity towards HbD and glycated HbD; or
one subpopulation of the one or more further subpopulations detects HbE, if present in the sample, and has bonded thereto a monoclonal antibody having selective binding affinity towards HbE and glycated HbE;
(b) with said analytes bound to the beads of said subpopulations, incubating said population with a labeled binding member that binds to all of said analytes, thereby labeling said analytes thus bound; and
(c) detecting the labeled binding member that binds to all of said analytes and detecting classifier dyes from the subpopulations of beads and differentiating the labels of the subpopulations by fluorescent emissions, thereby individually detecting HbA1c and if present, the hemoglobin variant.
3. The method of claim 2, wherein the population of beads further comprises a subpopulation that detects total hemoglobin, wherein each bead of the subpopulation to detect total hemoglobin has bonded thereto a classifier dye that is selected such that the classifier dye, and thereby said subpopulation, is differentiable from the other classifier dyes; and each member of said subpopulation that detects total hemoglobin having bonded thereto a monoclonal antibody having selective binding affinity towards all hemoglobin-containing analytes.
4. The method of claim 3, wherein said monoclonal antibody that has selective binding affinity towards all hemoglobin-containing analytes binds to a beta globin chain minimal epitope 9SAVTALWGKVNV20 (SEQ ID NO:15), 8KSAVTALWGKVNV20 (SEQ ID NO:16), or 11VTALW15 (SEQ ID NO:17).
5. The method of claim 2, wherein the antibody having selective binding affinity for HbA1c is a monoclonal antibody.
6. The method of claim 2, wherein one subpopulation of the one or more further subpopulations of (ii) detects HbD.
7. The method of claim 6, wherein the monoclonal antibody having selective affinity for HbD and glycated HbD is a monoclonal antibody that binds to a HbD minimal epitope 121QFTPP125 (SEQ ID NO:8) or 119GKQFTPP125 (SEQ ID NO:46).
8. The method of claim 2, wherein one subpopulation of the one or more further subpopulations of (ii) detects HbE.
9. The method of claim 8, wherein monoclonal antibody having selective affinity for HbE and glycated HbE is a monoclonal antibody that binds to a HbE minimal epitope 22EVGGK26 (SEQ ID NO:6) or 21DEVGGK26 (SEQ ID NO:7).
10. The method of claim 2, wherein the population comprises a subpopulation that detects HbD, if present in the sample, and a subpopulation that detects HbE, if present in the sample.
11. The method of claim 10, wherein the monoclonal antibody having selective binding affinity towards HbD and glycated HbD binds to a HbD minimal epitope 121QFTPP125 (SEQ ID NO:8) or 119GKQFTPP125 (SEQ ID NO:46); and the monoclonal antibody having selective affinity for HbE and glycated HbE binds to a HbE minimal epitope 22EVGGK26 (SEQ ID NO:6) or 21DEVGGK26 (SEQ ID NO:7).
12. The method of claim 2, wherein said method further comprises determining total hemoglobin in a non-immunoassay method.
13. The method of claim 2, wherein the blood cell lysate is a denatured blood cell lysate.
14. The method of claim 2, wherein the sample is from a diabetic patient.
15. A method for determining the proportion of HbA1c relative to total hemoglobin in a sample of blood cell lysate, adjusted for the possible presence in said lysate of a hemoglobin variant that interferes with the measurement of HbA1c, said method comprising:
(a) incubating said sample with a population of beads, said population consisting of a plurality of subpopulations in a common mixture, each bead of said population having bonded thereto one of a plurality of classifier dyes selected such that said classifier dyes, and thereby said subpopulations, are differentiable from each other by fluorescent emissions emitted by said classifier dyes upon excitation, each said subpopulation further having bonded thereto an immunological binding member having selective binding affinity toward one of a plurality of analytes, said plurality comprising HbA1c and said hemoglobin variant, to cause each of said analytes to bind to a different bead subpopulation through the immunological binding member bonded thereto;
(b) with said analytes bound to the beads of said subpopulations, incubating said population with a labeled binding member that binds to all of said analytes, thereby labeling said analytes so bound;
(c) with said bound analytes so labeled, detecting labels bound to said bound analytes while differentiating said labels so detected according to subpopulations by fluorescent emissions, thereby individually detecting concentrations of said analytes in said sample; and
(d) determining from said concentrations the proportion of HbA1c relative to total hemoglobin, adjusted for the concentration of said hemoglobin variant by an adjustment factor empirically derived from a predetermined relation between said hemoglobin variant concentration and the concentration of said HbA1c so detected.