Chemical apparatus and process disinfecting – deodorizing – preser – Analyzer – structured indicator – or manipulative laboratory... – Chemiluminescent
Reexamination Certificate
2001-01-16
2003-02-11
Snay, Jeffrey (Department: 1743)
Chemical apparatus and process disinfecting, deodorizing, preser
Analyzer, structured indicator, or manipulative laboratory...
Chemiluminescent
C250S36100C
Reexamination Certificate
active
06517777
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
This application relates generally to apparatus and methods for detecting and measuring analytes of interest by inducing electrochemiluminescence (ECL) in a test sample and detecting the resulting light.
Numerous methods and systems have been developed for detecting and quantitating analytes of interest in chemical, biochemical, biological, and environmental samples. Methods and systems that are capable of measuring toxins, environmental contaminants, pharmacological agents, bioactive substances, metabolites, pathogenic organisms, proteins and nucleic acids are of substantial value to researchers and clinicians. At this time, there are a number of commercially available instruments that utilize ECL for analytical measurements. These instruments have demonstrated exceptional performance.
The high cost, complex engineering and long development time required to custom-design and manufacture ECL instruments have delayed broad implementation of ECL technology. Clearly, there remains a need for ECL subsystems or modules that can be easily adapted to a broad variety of different applications.
Current needs for precision analytical testing instrumentation are extraordinarily diverse. For example, pharmaceutical screening analyses require instruments that can perform large numbers of analyses at very high speeds on very small quantities of sample. In addition, such instruments may need to perform many different types of highly sensitive quantitative tests utilizing different detection methods. Similarly, clinical diagnostic analyses for human health care typically require highly sensitive and exceptionally reliable instrumentation. In contrast, it is expected that commercial instruments intended for field use would be small, perhaps portable, simple to use, and operable with only limited power. Low production and maintenance costs are often predominant considerations.
2. Description of the Prior Art
An apparatus for carrying out electrochemiluminescence test measurements is found in U.S. Pat. No. 5,466,416 assigned to IGEN, Inc. A cross-sectional view of a flow cell is depicted in FIG.
1
. Flow cell
18
comprises a removable plug
20
, a gasket
22
, a retainer block
24
, a counter electrode
26
, an ECL test chamber
28
, a working electrode
30
, a transparent block
32
, a counter electrode
34
, a retainer block
36
, a conduit
46
, a main housing
48
, a chamber
40
, a lateral block
42
, a frit
44
, a gasket
50
, a plug
52
, an O-ring seal
56
, a threaded coupling
58
, a conduit
60
, a pivot arm
61
, a magnet
62
, and a threaded coupling
64
.
Flow cell
18
includes a main housing
48
formed of a durable, transparent and chemically inert material such as acrylic or polymethyl methacrylate. Threaded coupling
64
defines a fluid inlet in a lower surface of housing
48
and is contiguous with conduit
46
. Conduit
46
extends through housing
48
from coupling
64
to an upper surface of housing
48
. Threaded coupling
58
defines a fluid outlet in a lower surface of housing
48
and is contiguous with conduit
60
. Conduit
60
extends through housing
48
from coupling
58
to the upper surface of housing
48
. ECL test chamber
28
is bounded by the upper surface of housing
48
, a lower surface of block
32
, lower and side surfaces of counter electrodes
26
and
34
, the upper surface of working electrode
30
, and the interior surface of gasket
22
. Chamber
28
communicates with both conduit
60
and conduit
46
. Fluid introduced through coupling
64
may travel through conduit
46
to chamber
28
and exit through conduit
60
and coupling
58
.
Working electrode
30
, counter electrode
26
, and counter electrode
34
may consist of electrically-conductive materials such as platinum or gold. Working electrode
30
has a generally flat, elongate, rectangular shape having a longitudinal axis arranged generally transverse to a longitudinal axis of chamber
28
. Electrode
30
is positioned centrally between conduits
60
and
46
in a shallow groove formed in the upper surface of housing
48
. An adhesive (not shown) bonds electrode
30
to the groove in housing
48
. Accordingly, at least three seams between electrode
30
and housing
48
abut chamber
28
; one on each latitudinal side of electrode
30
and a third at a longitudinal end of electrode
30
. As displayed in
FIG. 1
, electrode
30
is approximately as wide as the gap between counter electrodes
26
and
34
and is positioned centrally therebetween.
Counter electrodes
26
and
34
have an “L”-shaped cross-section, the shorter arm having a length slightly longer than the thickness of block
32
and the longer arm having a length of less than half of the width of block
32
. The two arms of each electrode are flat, thin and positioned perpendicular to each other but in different planes. The widths of electrodes
26
and
34
are approximately less than half of the thickness of block
32
. Counter electrode
26
is affixed to a side of transparent block
32
and is held in place by retainer block
24
. On the opposite side of transparent block
32
, counter electrode
34
is similarly affixed by retainer block
36
.
Magnet
62
is affixed to pivot arm
61
. In its raised position, pivot arm
61
positions magnet
62
beneath working electrode
30
, sandwiching a segment of housing
48
therebetween. In its lowered position, pivot arm
61
pivots down and away from housing
48
thereby significantly increasing the distance between working electrode
30
and magnet
62
.
A reference electrode assembly, integrated into housing
48
, comprises chamber
40
, block
42
, gasket
50
, frit
44
, plug
52
, and gasket
56
. An ionic fluid (not shown) is retained within chamber
40
. Chamber
40
comprises a cavity defined by housing
48
, gasket
50
and block
42
. Frit
44
extends into conduit
60
and is sealed by O-ring
56
and plug
52
.to prevent fluidic interchange.
A refill aperture (not shown) is provided in housing
48
to allow replacement of the ionic fluid held in chamber
40
. The refill aperture is sealed by removable plug
20
. To achieve useful and reproducible ECL test measurements, flow cell
18
utilized a temperature-controlled environment.
FIG. 2
illustrates an apparatus
80
from U.S. Pat. No. 5,466,416 for providing a temperature-controlled environment for flow cell
18
. Apparatus
80
comprises a photomultiplier tube (PMT)
82
, an insulating cover
92
, a housing
94
, a plurality of foil heaters
96
, a circuit board
84
, flow cell
18
, a magnet
62
, a pivot arm
61
, a linear actuator
98
, a coil spring
102
, an air space
90
, and a fan
104
. For reference purposes, housing
48
, block
42
, retainer block
24
, counter electrode
26
, and block
32
are specifically labelled on flow cell
18
.
Foil heaters
96
are positioned on the outer lateral surfaces and the outer lower surface of housing
94
. The upper surface of housing
94
adjacent PMT
82
is formed of a transparent material while the remaining portions of housing
94
are preferable opaque. Insulating cover
92
covers foil heaters
96
as well as the remaining uncovered outer surfaces of housing
94
to provide thermal insulation and prevent the entry of light into flow cell
18
. PMT
82
is a conventional photomultiplier tube mounted on the upper surface of housing
94
. PMT
82
is physically large compared to the size of the flow cell, requires a high-voltage power supply, and is highly sensitive to the surrounding temperature and the presence of magnetic fields. It is preferable that PMT
82
be maintained at a relatively low temperature. Flow cell
18
is positioned below PMT
82
inside temperature-controlled housing
94
.
Circuit board
84
, incorporating operating electronics for apparatus
80
, is mounted on an interior surface of housing
94
adjacent flow cell
18
. As shown, linear actuator
98
is connected to coil spring
102
which, in turn, is connected to pivot arm
61
. Magnet
62
is affixed to an end of pivot arm
61
.
The
Gambrel David R.
Ivanov Sergey
Liljestrand John
Wohlstadter Jacob N.
Zhang Jue
IGEN International Inc.
Kramer Levin Naftalis & Frankel LLP
Snay Jeffrey
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