Methods and apparatus for reference lab diagnostics
Automated protein assay apparatus and methods suitable for use in a reference lab are described. A screening test for a pathogen or disease condition is performed at the reference lab. If the results of the screening test are positive, a definitive assay is performed. One or more analytes are resolved in a fluid path such as that of a capillary by isoelectric focusing. The resolved analytes are immobilized in the capillary by photoimmobilization. A typical analyte is a protein of a biological sample of a subject. Detection agents such as antibodies are flowed through the capillary which bind to or interact with the analytes, forming antibody-protein complexes. A chemiluminescent substrate is flowed through the capillary and detected with a photon detector. The detected locations of the analytes are recorded and the results sent to the referring physician. The assay is preferably performed by a computer-controlled, automated system exhibiting speed, precision and repeatability which are highly desirable for a reference lab diagnostic test.
1 . A method for performing a protein assay in a reference lab comprising:
receiving a biological sample for analysis;
loading the biological sample into a capillary;
resolving analytes of the sample in the capillary;
immobilizing the resolved analytes in the capillary;
binding detection agents to the immobilized analytes;
detecting the location of agent-analyte complexes;
recording results from the detection;
sending the results to a recipient.
2 . The method of claim 1 , wherein receiving is following by performing a screening test on the biological sample.
3 . The method of claim 2 , wherein performing a screening test comprises performing an ELISA assay.
4 . The method of claim 2 , wherein receiving is followed by logging information about the biological sample into a reference lab database.
5 . The method of claim 1 , wherein resolving comprises resolving analytes in the capillary by isoelectric focusing.
6 . The method of claim 5 , wherein binding comprises binding antibodies to the immobilized analytes.
7 . The method of claim 6 , wherein detecting is preceded by flowing a chemiluminescent substrate through the capillary.
8 . The method of claim 1 wherein the steps of resolving, immobilizing, binding and detecting are performed by an integrated automated computer-controlled assay system.
9 . The method of claim 8 , wherein the integrated automated computer-controlled assay system further performs the step of loading.
10 . In a diagnostic reference lab, an automated assay system for detecting the presence of proteins in biological samples comprising:
a processing station;
a capillary gripper which is operable to manipulate capillaries at the processing station; and
a detection station, wherein the capillary gripper is further operable to manipulate capillaries containing a biological sample at the detection station,
wherein the presence of proteins in the biological sample is detected at the detection station.
11 . The automated assay system of claim 10 , wherein the capillary gripper further comprises an automated, computer-controlled capillary gripper.
12 . The automated assay system of claim 11 , wherein the capillary gripper is operable to mechanically grip a capillary.
13 . The automated assay system of claim 11 , wherein the capillary gripper is operable to mechanically grip a capillary by a vacuum.
14 . The automated assay system of claim 10 , wherein the capillary gripper is further operable to load a biological sample into a capillary at the processing station.
15 . The automated assay system of claim 10 , further comprising a microtiter plate located at the processing station.
16 . The automated assay system of claim 10 , further comprising a photon detector located at the detection station.
17 . The automated assay system of claim 10 , further comprising a user interface for configuring a protocol by which the automated assay system is to analyze the biological sample.
18 . The automated assay system of claim 17 , wherein the user interface is also operable to display detection results.
19 . A method for performing an assay in a reference lab comprising:
resolving pathogen-derived analytes in a capillary;
immobilizing the resolved analytes in the capillary;
loading patient-derived serum into the capillary;
allowing binding of patient-serum-derived antibodies to the immobilized analytes;
detecting the location of serum-derived antibodies by means of a detection agent;
recording results from the detection; and
sending the results to a recipient.
20 . The method of claim 19 , wherein resolving is preceded by performing a screening test on the patient-derived serum.
21 . The method of claim 20 , wherein performing a screening test comprises performing an ELISA assay.
22 . The method of claim 20 , wherein detecting further comprises detecting the location of analytes which are particular to HIV.
23 . The method of claim 20 , wherein detecting further comprises detecting the location of analytes which are particular to Lyme disease.
24 . The method of claim 19 , wherein resolving comprises resolving analytes in the capillary by isoelectric focusing.
25 . The method of claim 24 , wherein allowing binding comprises allowing antibodies to bind to the immobilized analytes.
26 . The method of claim 25 , wherein detecting is preceded by flowing a chemiluminescent substrate through the capillary.
27 . The method of claim 19 , wherein the steps of resolving, immobilizing, loading and detecting are performed by an integrated automated computer-controlled assay system.
28 . A method for performing a protein assay in a reference lab comprising:
receiving a biological sample for analysis;
treating the sample with a protease discriminatory between pathogenic and normal forms of a protein;
loading the protease-treated biological sample into a capillary;
resolving analytes of the sample in the capillary;
immobilizing the resolved analytes in the capillary;
binding detection agents to the immobilized analytes;
detecting the location of agent-analyte complexes;
recording results from the detection; and
sending the results to a recipient.
29 . The method of claim 28 , wherein receiving is followed by performing a screening test on the biological sample.
30 . The method of claim 29 , wherein performing a screening test comprises performing an ELISA assay.
31 . The method of claim 30 , wherein resolving comprises resolving analytes in the capillary by isoelectric focusing.
32 . The method of claim 31 , wherein detecting is preceded by flowing a chemiluminescent substrate through the capillary.
33 . The method of claim 28 , wherein the steps of loading, resolving, immobilizing, binding and detecting are performed by an integrated automated computer-controlled assay system.
34 . The method of claim 28 , wherein the pathogenic form of the protein results from one of bovine spongiform encephalopathy (“mad cow” disease), scrapie or Creutzfeldt-Jakob disease.