Chemistry: analytical and immunological testing – Automated chemical analysis – With a continuously flowing sample or carrier stream
Reexamination Certificate
1998-07-06
2002-02-19
Warden, Jill (Department: 1743)
Chemistry: analytical and immunological testing
Automated chemical analysis
With a continuously flowing sample or carrier stream
C436S052000, C436S054000, C436S180000, C422S063000, C422S081000, C422S105000, C422S105000, C422S108000
Reexamination Certificate
active
06348354
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to a capsule chemistry sample liquid analysis system adapted for the automated clinical analysis of pluralities of human biological sample liquids, in particular to a method and apparatus for controlling a stream of liquid test packages flowing through such a system.
BACKGROUND
U.S. Pat. No. 5,268,147 (the “'147 patent”) and U.S. Pat. No. 5,399,497 (the “'497 patent”), owned by the assignee hereof, the disclosures of which are incorporated herein by reference, describe a capsule chemistry sample liquid analysis system which operates through repeated reversible, bi-directional flow of an appropriately configured stream of liquid test packages, each test package consisting of alternating segments of a liquid, such as a sample, reagent or buffer, and air, to enable repeated, precisely timed analysis of the sample of each of the test packages in the stream by one or more sample liquid analysis means. As described in the '147 and '497 patents, the system generally comprises a sample liquid test package metering and supply means which operates to meter successive test packages for reaction and analysis within the system; a reversible direction sample liquid test package displacement means which operates to bi-directionally displace the thusly metered and supplied test packages through the system; a test package transfer means which operates in conjunction with the test package metering and supply means and the test package displacement means to provide for the successive test package supply and bi-directional functions of the system; test package reaction and analysis means for analysis of the thusly supplied and displaced text packages; and detection means operatively associated with the reaction and analysis means to detect and quantify the successive sample liquid test package analysis results. Such a system is particularly adapted to conduct automated clinical analysis of pluralities of human biological sample liquids and can be configured to perform various specific analyses, including well known so called chemistry and immunoassay analyses.
An embodiment of the system just described configured for conducting a chemistry analysis is shown in
FIG. 1A. A
second embodiment of the system just described configured for conducting an immunoassay analysis is shown in FIG.
1
B.
As described in detail in the '147 and '497 patents, the system generally operates by creating a plurality of test packages and successively inserting the test packages into analytical line
30
shown in
FIGS. 1A and 1B
, which preferably comprises a flexible conduit made of transparent Teflon or like material. The test packages are then repeatedly and bi-directionally flowed back and forth in the analytical line
30
and ultimately past the appropriate test package reaction, analysis and detection means. Depending on the type of analysis being done, e.g., chemistry or immunoassay, particular devices are disposed along the analytical line
30
so as to comprise the reaction, analysis and detection means. As shown in
FIG. 1A
, a configuration appropriate for a chemistry analysis includes first, second and third flow cells
45
and vanish zone
50
disposed along the analytical line
30
. The functionality of these components is described in greater detail both below and in the '147 and '497 patents. As shown in
FIG. 1B
, a configuration appropriate for an immunoassay analysis includes vanish zone
50
, first, second and third bubble detectors
55
, first and second magnets
60
and luminometer
65
. The functionality of these components is described in greater detail both below and in the '147 and '497 patents.
It will be apparent to one of skill in the art that a test package suitable for a so-called sandwich type magnetic particle-based heterogeneous immunoassay is as shown in FIG.
2
. In particular, this test package consists of six liquid segments: a magnetic particle suspension designated as MP, a mixture of sample and first and second reagents designated as S/R
1
/R
2
, a first wash designated as W
1
, a second wash designated as W
2
, a combination of a third reagent and a fourth reagent designated as R
3
/R
4
, and a marker dye designated as D. As illustrated in
FIG. 2
, each of these liquid segments is separated by an air segment designated as A
1
/A
3
, which is a combination of successively metered air segments A
1
and A
3
, or an air segment designated as A
2
. It will also be apparent to one of skill in the art that other suitable immunoassay test packages exist, for example a test package containing eight liquid segments.
It will also be apparent to one of skill in the art that a suitable test package for a chemistry analysis is as shown in FIG.
3
. In particular, this test package consists of three liquid segments: a second reagent designated as R
2
, a mixture of sample and a first reagent designated as S/R
1
, and a buffer designated as B. As shown in
FIG. 3
, with the exception of the S/R
1
and R
2
segments, each of these liquid segments is separated by an air segment designated as A
1
, A
2
and A
3
. The S/R
1
and R
2
segments are separated by a vanish bubble VB comprising air. As described in detail in the '147 and '497 patents, this vanish bubble VB operates in connection with vanish zone
50
shown in
FIG. 1A
to cause a mixing of the S/R
1
and R
2
segments at an appropriate lime.
Referring again to
FIGS. 1A and 1B
, the sample liquid test package metering and supply means which creates the test packages described above includes an aspirating probe
10
connected to a service loop
15
which, like analytical line
30
, preferably comprises a flexible conduit made of transparent Teflon or like material. Liquid supply
20
is located adjacent probe
10
and generally comprises a plurality of containers for holding and supplying the various liquids to be aspirated into the probe
10
including sample liquids, reagents, marker dyes, magnetic particle suspensions, buffers and washes.
Thus, the test packages just described are created in one or more cycles involving the alternate aspiration of segments of liquid from the liquid supply
20
and segments of air. In particular, with respect to the creation of a sandwich type immunoassay test package, during each cycle, two liquid segments, L
1
and L
2
, and three air segments, A
1
, A
2
and A
3
, are alternatively aspirated into the probe
10
and up into the service loop
15
by operation of aspiration pump
25
, which is selectively coupled to the service loop
15
through transfer line
35
and shear valve
40
, to be described below, to create a test package component shown in FIG.
4
. The order of aspiration during each cycle to create a test package component is as follows: A
3
, L
2
, A
2
, L
1
, A
1
. Thus, a sandwich type immunoassay test package as shown in
FIG. 2
is created by aspirating three successive test package components, designated as TPC-
1
, TPC-
2
and TPC-
3
in
FIG. 2
, in three successive cycles. In cycle
1
, TPC-
1
is aspirated wherein L
2
is the mixture of sample and first and second reagents S/R
1
/R
2
and L
1
is the magnetic particle suspension MP. In cycle
2
, TPC-
2
is aspirated wherein L
2
is the second wash W
2
and L
1
is the first wash W
1
. In cycle
3
, TPC-
3
is aspirated wherein L
2
is the marker dye D and L
3
is the combination of third and fourth reagents R
3
/R
4
.
FIG. 5
illustrates this creation in three cycles. As shown in
FIG. 5
, adjacent test package components always abut one another at an A
1
/A
3
interface. The chemistry test package, on the other hand, is simply created in one cycle by aspirating a third air segment A
3
, then the buffer B, then a second air segment A
2
, then the mixture of sample and first reagent S/R
1
, then the vanish bubble VB, then the second reagent R
2
, and finally a first segment A
1
.
In addition, as described in the '147 and '497 patents, an isolation liquid is aspirated into the probe
10
each time a liqui
Adolfsen Robert
Gherson Paul
Lightbody David
Bayer Corporation
Gordon Brian R.
Klawitter Andrew L.
Paolino John M.
Warden Jill
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