U.S. patent application number 10/158495 was filed with the patent office on 2003-12-04 for clinical tester wash and method.
Invention is credited to Ravalico, Patricia H., Wilson, Charlie W. III.
Application Number | 20030223472 10/158495 |
Document ID | / |
Family ID | 29582700 |
Filed Date | 2003-12-04 |
United States Patent
Application |
20030223472 |
Kind Code |
A1 |
Ravalico, Patricia H. ; et
al. |
December 4, 2003 |
Clinical tester wash and method
Abstract
A clinical tester has been described that includes a probe to
aspirate a fluid. The probe is washed between aspirations to reduce
carryover. The wash operation includes both an internal and an
external wash, where the internal wash operation is terminated
prior to terminating the external wash. In one embodiment, the
probe wash can be implemented on an integrated clinical
chemistry/immunoassay tester.
Inventors: |
Ravalico, Patricia H.;
(Keller, TX) ; Wilson, Charlie W. III; (N.
Richland Hills, TX) |
Correspondence
Address: |
STEVEN F. WEINSTOCK
ABBOTT LABORATORIES
100 ABBOTT PARK ROAD
DEPT. 377/AP6A
ABBOTT PARK
IL
60064-6008
US
|
Family ID: |
29582700 |
Appl. No.: |
10/158495 |
Filed: |
May 29, 2002 |
Current U.S.
Class: |
374/31 ;
374/35 |
Current CPC
Class: |
G01N 35/1016 20130101;
G01N 2035/1006 20130101; B08B 3/02 20130101; G01N 35/1004 20130101;
Y10T 436/114998 20150115; Y10T 436/115831 20150115; G01N 35/10
20130101; G01N 2035/00277 20130101; B08B 3/04 20130101; Y10T 436/12
20150115 |
Class at
Publication: |
374/31 ;
374/35 |
International
Class: |
G01K 017/00 |
Claims
1. A fluid tester comprising: a probe having an interior region and
an exterior surface, wherein the sample probe is used to
selectively aspirate a fluid into the interior region; a first wash
mechanism coupled to the probe to dispense a wash fluid through the
interior region of the probe for a first predetermined period; and
a second wash mechanism located to dispense the wash fluid on the
exterior surface of the probe for a second predetermined period,
wherein the second predetermined period extends beyond the first
predetermined period.
2. The fluid tester of claim 1 wherein the aspirated fluid is 15
.mu.L or less in volume and the second predetermined period is
about one second and the second predetermined period extends about
0.1 second beyond the first predetermined period.
3. The fluid tester of claim 1 wherein the second wash mechanism is
a cup having at least one wash fluid nozzle directed toward a
center area of the cup.
4. A clinical analyzer comprising: a sample probe arm comprising a
probe having an interior region and an exterior surface, wherein
the probe is used to selectively aspirate a test sample into the
interior region; a sample wash mechanism coupled to the sample
probe arm to dispense a sample wash fluid through the interior
region of the probe for a first predetermined period; and a sample
wash station to receive the probe and dispense the sample wash
fluid on the exterior surface of the probe for a second
predetermined period, wherein the second predetermined period
extends beyond the first predetermined period.
5. The clinical analyzer of claim 4 further comprising a reagent
probe arm to aspirate a reagent.
6. The clinical analyzer of claim 5 further comprising: a reagent
wash mechanism coupled to the reagent probe arm to dispense a
reagent wash fluid through an interior region of a reagent probe
for a third predetermined period; and a reagent wash station to
receive the reagent probe and dispense the reagent wash fluid on
the exterior surface of the reagent probe for a fourth
predetermined period, wherein the fourth predetermined period
extends beyond the third predetermined period.
7. The clinical analyzer of claim 4 wherein the second
predetermined period is about one second and the second
predetermined period extends about 0.1 second beyond the first
predetermined period.
8. The clinical analyzer of claim 4 further comprising: a sample
transporter to transport a sample container containing a test fluid
used to aspirate the test sample; a chemistry analyzer coupled to
sample the test fluid located on the sample transporter; and an
immunoassay analyzer coupled to sample the test fluid located on
the sample transporter.
9. The clinical analyzer of claim 4 wherein the immunoassay
analyzer comprises: a second sample probe arm comprising a second
probe having an interior region and an exterior surface, wherein
the second probe is used to selectively aspirate a second test
sample into the interior region of the second probe; a second
sample wash mechanism coupled to the second sample probe arm to
dispense the sample wash fluid through the interior region of the
second probe for a third predetermined period; and a second sample
wash station to receive the second probe and dispense the sample
wash fluid on the exterior surface of the second sample probe for a
fourth predetermined period, wherein the fourth predetermined
period extends beyond the third predetermined period.
10. A probe cleaning system comprising: a wash pump coupled to
dispense a wash fluid through an interior region of the probe for a
first predetermined time period; and a second wash pump located to
dispense the wash fluid on an exterior surface of the probe for a
second predetermined period, wherein the second predetermined
period extends beyond the first predetermined period.
11. The probe cleaning system of claim 10 wherein a difference
between a termination time of the first predetermined period and a
termination time of the second predetermined time period is about
ten percent (10%) of the second predetermined period.
12. A method of cleaning a fluid probe comprising: flushing an
interior region of the fluid probe with a wash fluid for X seconds;
and simultaneously flushing an exterior surface of the fluid probe
with the wash fluid for Y seconds, wherein Y is greater than X.
13. The method of claim 12 where a difference between a termination
time of the interior region flush and a termination time of the
exterior surface flush is about 0.1 Y.
14. The method of claim 13 where Y is approximately one second.
15. A method of reducing sample carryover in an integrated
chemistry and immunoassay analyzer comprising: aspirating a first
test sample from a first sample container using a probe; depositing
the first test sample into a reaction vessel; performing a clinical
analysis of the test sample; washing the probe by pumping a wash
fluid through an interior region of the probe and pumping the wash
fluid on an exterior of the probe, wherein the pumping of the wash
fluid is terminated from the interior region prior to terminating
the pumping of the exterior; and aspirating a second test sample
from a second sample container using the probe.
16. The method of claim 15 wherein the pumping of the wash fluid on
the exterior starts prior to pumping the wash fluid through the
interior region.
17. The method of claim 16 wherein the wash fluid is pumped on the
exterior for about one second.
18. The method of claim 17 wherein the pumping of the wash fluid
through the interior region is terminated about 0.1 seconds prior
to terminating the pumping of the wash fluid on the exterior.
19. The method of claim 15 further comprising: aspirating a second
test sample from the first sample container using a second probe;
depositing the second test sample into a second reaction vessel;
and performing an immunoassay analysis of the second test
sample.
20. The method of claim 19 wherein the clinical analysis is either
a chemistry or immunoassay analysis.
21. A method of cleaning a probe comprising: activating a first
pump to pump a wash fluid through an interior region of the probe;
activating a second pump to pump the wash fluid onto an exterior
region of the probe; deactivating the first pump after a first
predetermined time period; and deactivating the second pump after a
second predetermined time period, wherein the second predetermined
time period is longer than the first predetermined time period.
22. A method of washing a probe comprising: determining an amount
of fluid to be aspirated inside the probe; and selecting an
external wash profile in response to the amount of fluid aspirated
inside the probe.
23. The method of claim 22 wherein the wash profile comprises a
first wash sequence having both an internal and external probe
wash, and an extended external wash if the amount of fluid
aspirated exceeds a predetermined threshold.
24. The method of claim 23 wherein the extended external wash is
about three times as long as the first wash sequence.
25. A method of reducing carryover in a clinical tester as a result
of external probe contamination comprising: inserting the probe
into a fluid; determining an amount of fluid to be aspirated inside
the probe; dispensing the aspirated fluid; washing the inside of
the probe; and selecting an external wash profile in response to
the amount of fluid aspirated inside the fluid probe, wherein an
extended external wash is provided if the amount of fluid aspirated
exceeds a pre-determined amount.
Description
FIELD OF THE INVENTION
[0001] The present invention relates generally to clinical test
equipment and in particular the present invention relates to
reduction of sample carryover in clinical test equipment.
BACKGROUND OF THE INVENTION
[0002] Although various known clinical analyzers for chemical,
immunochemical and biological testing of samples are available,
clinical technology is rapidly changing due to increasing demands
in the clinical laboratory to provide new levels of service. These
new levels of service must be more cost effective to decrease the
operating expenditures such as labor cost and the like, and must
provide shorter turnaround time of test results. Modernization of
analytical apparatus and procedure demands consolidation of
workstations to meet the growing challenge placed on clinical
laboratories.
[0003] Generally, analysis of a test sample involves the reaction
of test samples with one or more reagents with respect to one or
more analytes wherein it is frequently desired that the analysis be
performed on a selective basis with respect to each test sample.
Automated clinical analysis systems analyze a test sample for one
or more characteristics. Automated clinical analyzers also provide
results much more rapidly while frequently avoiding operator or
technician error, thus placing emphasis on accuracy and
repeatability of a variety of tests. Automated clinical analyzers
presently available for routine laboratory tests include a
transport or conveyor system designed to transport containers of
sample liquids between various operating stations.
[0004] Some of the presently available automated clinical
analyzers, such as automated immunoassay analyzers, utilize
procedures involving a variety of different assay steps. A robotic
arm automatically processes the test samples with a probe and a
carousel, or robotic track, that positions the samples for
processing. A typical tester has a sample probe arm to sample
fluids and deposit the samples in a reaction vessel. One or more
reagents are added to the vessel using reagent probe arms. The
sample and reagent probe arms include a probe that can be moved
between sample or reagent locations, the reagent vessel and wash
stations.
[0005] Clinical chemistry and immunoassay testers have
traditionally been standalone systems. These systems can be
combined using a common transport system to provide a more
efficient integrated system. Previous standalone chemistry
analyzers did not require sample-to-sample carryover performance
requirements of an integrated clinical chemistry and immunoassay
system. As laboratories integrate automated analytical systems,
between-sample carryover becomes a critical goal. Many companies
have elected to overcome this problem through use of disposable
probe tips, but this approach is costly, wasteful and less
reliable. Another safeguard is to prioritize test sequencing such
that immunoassay sampling is done prior to all chemistry tests.
This approach impacts chemistry turnaround time and lowers total
workflow throughput. Yet another method to reduce sample carryover
is to flush the system with large amounts of fluids (buffer, water,
detergents).
[0006] For the reasons stated above, and for other reasons stated
below which will become apparent to those skilled in the art upon
reading and understanding the present specification, there is a
need in the art for a reduction in sample carryover in clinical
test equipment.
SUMMARY OF THE INVENTION
[0007] The above-mentioned problems with sample carryover and other
problems are addressed by the present invention and will be
understood by reading and studying the following specification.
[0008] In one embodiment, a fluid tester comprises a probe having
an interior region and an exterior surface. The probe is used to
selectively aspirate a fluid into the interior region. A first wash
mechanism is coupled to the probe to dispense a wash fluid through
the interior region of the probe for a first predetermined period.
A second wash mechanism is located to dispense the wash fluid on
the exterior surface of the probe for a second predetermined
period. The second predetermined period extends beyond the first
predetermined period.
[0009] In another embodiment, a method of cleaning a probe
comprises flushing an interior region of the probe with a wash
fluid for X seconds, and simultaneously flushing an exterior
surface of the probe with the wash fluid for Y seconds, wherein Y
is greater than X.
[0010] A method of sample carryover in an integrated chemistry and
immunoassay analyzer comprises aspirating a first test sample from
a first sample container using a probe, depositing the first test
sample into a reaction vessel and performing a chemical analysis of
the test sample. The probe is washed by pumping a wash fluid
through an interior region of the probe and pumping the wash fluid
on the exterior of the probe. The pumping of the wash fluid is
terminated from the interior region prior to terminating the
pumping of the exterior. A second test sample is then aspirated
from a second sample container using the probe.
BRIEF DESCRIPTION OF THE DRAWINGS
[0011] FIG. 1A is a perspective view of a clinical tester of an
embodiment of the present invention;
[0012] FIG. 1B is a clinical chemistry analyzer of the tester of
FIG. 1A;
[0013] FIG. 1C is an immunoassay analyzer of the tester of FIG.
1A;
[0014] FIG. 2 illustrates a probe arm of the clinical tester of
FIG. 1; and
[0015] FIG. 3 is a simplified cross-section of a probe in a wash
station.
DETAILED DESCRIPTION OF THE DRAWINGS
[0016] In the following detailed description of the preferred
embodiments, reference is made to the accompanying drawings, which
form a part hereof, and in which is shown by way of illustration
specific preferred embodiments in which the inventions may be
practiced. These embodiments are described in sufficient detail to
enable those skilled in the art to practice the invention, and it
is to be understood that other embodiments may be utilized and that
logical, mechanical and electrical changes may be made without
departing from the spirit and scope of the present invention. The
following detailed description is, therefore, not to be taken in a
limiting sense, and the scope of the present invention is defined
only by the claims.
[0017] The term "test sample", as used herein, refers to a test
material that can be used directly as obtained from a source or
following a pretreatment to modify the character of the sample. The
test sample can be derived from any biological source, such as
physiological fluid, including, whole blood, serum, plasma, saliva,
ocular lens fluid, cerebral spinal fluid, sweat, urine, milk,
ascites fluid, raucous, synovial fluid, peritoneal fluid, amniotic
fluid or the like.
[0018] The term "carryover" refers to cross-contamination or
contact transfer between test samples. Carryover is a byproduct of
using a common sample probe for multiple test samples.
[0019] Between-sample carryover is a critical factor to ensure
result integrity on automated analytical systems. Immunoassay
analyzers traditionally meet a sample-to-sample carryover goal of
less than 0.1 ppm. Clinical chemistry systems utilize methodologies
that are less sensitive and rarely characterized using carryover
requirements to this level. As laboratories consolidate analytical
systems, however, the between-sample carryover demands for
immunoassay analyzers become applicable to clinical chemistry
systems as well. Achieving a between-sample carryover goal of less
than 0.1 ppm for an integrated immunoassay and clinical chemistry
system can impact marketability of other variables including
specimen throughput, system consumables, test prioritization, and
sample pre-aliquoting.
[0020] Extensive research on an integrated system of an embodiment
of the present invention identified critical variables associated
with sample-to-sample carryover. High-speed video was used for
qualitative characterization of the sample probe wash while
concentrated samples of hepatitis surface-antigen (HbsAg) were used
to quantitatively assess carryover performance. A probe wash
protocol of an embodiment of the invention passes the
between-sample carryover limit of 0.1 ppm without sample
pre-aliquoting, use of additional consumables, test prioritization,
or significant impact to system specimen throughput. Critical
variables include clinical chemistry sampling/aspiration volumes
and external sample probe wash duration, sequencing relative to the
internal sample probe wash. Other variables include positioning of
the sample probe within the sample wash cup, sample wash cup design
and external sample wash flow volumes/rates.
[0021] An embodiment of a wash protocol dictates the between sample
wash mechanism based on clinical chemistry sampling volume. The
wash includes an external wash and an internal wash of the sample
probe. All specimens with a maximum chemistry sampling volume below
a predetermined threshold (such as 15 .mu.L or less) are
effectively washed using an extended single cycle wash mechanism.
It is noted that a `dummy` fluid volume may be aspirated in
addition to the fluid sample volume. The dummy volume provides a
buffer between the sample fluid and residual fluid in the probe.
The dummy volume is not included in the sample volume levels
described herein. The extended single cycle wash mechanism utilizes
a one second external probe wash that ends 100 ms after the
internal probe wash. This timing relationship between the internal
and external wash sequencing is particularly crucial for acceptable
carryover performance. Specimens that are processed with chemistry
sampling volumes exceeding the threshold (15.1 .mu.L or more) are
washed using the same extended single cycle wash mechanism but also
undergo an additional 3.2 seconds of supplemental external wash.
The wash protocol of the present invention, as explained below, is
not limited to a specific timing duration or over-lap time between
the termination of internal and external washes.
[0022] Between-Sample Carryover was quantitatively evaluated using
recombinant samples of concentrated hepatitis surface-antigen
(HbsAg) in a pooled human serum matrix. Each concentrated HBsAg
sample (with approximate immuno-reactivity of 4 mg/mL) was followed
by pooled normal human serum (pre-screened non-reactive for HbsAg)
and processed on a chemistry analyzer. The pooled human serum
samples were evaluated on an immunoassay analyzer for HbsAg
activity. Results were compared against serial dilutions of the
concentrated stock. If the pooled human serum results exceeded that
of the 0.1 ppm dilution of the concentrated stock, a test run was
considered a failure. The magnitude of the failure was calculated
by converting the reported concentration of the serum diluents into
units of ppm from the reference dilution. Test conditions were
created to represent worst-case performance and test result
confidence. The clinical chemistry sample volume was defined at 35
.mu.L, a typical maximum sample volume for a chemistry application.
HbsAg samples were processed in duplicate to ensure result
integrity.
[0023] Results demonstrated a sample carryover performance trend
associated with sample probe aspiration volume. As the clinical
chemistry sample volume increases, between-sample carryover
failures also increase. Most systems fail between-sample carryover
with a frequency higher than 50% (without optimization critical
parameters) at the maximum clinical chemistry sampling volume of 35
.mu.L. The relationship between sample volume and sample-to-sample
carryover performance is significant to understanding the mode of
failure. This is because trending demonstrates that internal
contamination of the sample probe has an impact on sample-to-sample
carryover. The sample probe aspirates a test sample from a sample
tube and immediately dispenses the sample volume into a reaction
vessel prior to entrance into a wash station. An over-aspiration or
dummy volume is dispensed at the wash station but this volume is
consistent and independent of chemistry sample volume (under the
protocol test conditions). Since the frequency of the carryover
increases with chemistry sample volume and since this sample volume
is dispensed prior to external wash of the probe, it was theorized
that the source of the carryover (leading to the between-sample
failures) resulted from internal contamination of the sample probe.
This theory was supported by a supplemental investigation that
demonstrated that carryover failures were still prevalent without
any dummy/over aspiration being dispensed at the sample wash
station. Residual carryover remained on the external surface of the
sample probe following sample probe washing, even when the probe
did not dispense any concentrated sample at the wash station. The
frequency of sample carryover failures can be reduced using
supplemental probe washes. Unfortunately, supplemental washes
require additional instrument cycles that can degrade system
specimen throughput.
[0024] A second variable to carryover performance is wash
sequencing at the sample wash station. Further analysis of wash
conditions at the sample wash station lead to a study evaluating
external wash sequencing relative to the internal wash. Success of
the probe wash was less dependent on the external wash duration
than it was on the stop sequencing of the external wash relative to
the internal wash. If the internal wash stops after the external
wash, carryover performance is significantly worse than if the
external wash if ends after the internal wash. This relationship
supports a theory that internal contamination of the probe is a
source for the external between-sample carryover. One wash protocol
utilizes a one second external probe wash that extends beyond the
stop time of the internal wash to improve carryover performance at
low sample volumes. A supplemental washing that would have required
an additional instrument cycle is not required to meet carryover
performance criteria.
[0025] Further studies demonstrated additional variables associated
with between-sample carryover performance. These include wash cup
design, hardware alignment at the sample wash station, and wash
flow rates/volume. These variables are significant and require
optimization for carryover performance. Failure to optimize these
parameters can cause carryover failures. However, optimization, of
these parameters will not create a passing condition without
control of the critical variables of chemistry sampling volume and
wash sequencing.
[0026] Referring to FIG. 1A, a perspective view of a simplified
integrated clinical test system 100 of an embodiment of the present
invention. The test system includes a clinical chemistry tester 102
and an immunoassay tester 104, see FIGS. 1B and 1C for more detail.
The two testers share a common sample transporter 106 that allows
linear movement of test sample tubes 108 between the two
testers.
[0027] Each tester has a sample probe arm 110/112 that includes a
probe 114 (see FIG. 2). The arms can move in both a horizontal arc
and vertical directions. The probe aspirates a test sample from
tube 108 located on the transporter 106. The probe arm then moves
to a sample vessel (not shown) and deposits the aspirated sample.
After the sample has been discharged from the probe, the arm moves
to a wash station 120 where the probe is washed. The sample vessel
is moved to a location where a reagent is added to the sample by a
reagent arm 122. The reagent arm is movable between a reagent
location, the sample vessel and the wash station. The sample vessel
may receive additional reagents and is then subjected to chemistry
testing, as know to those skilled in the art. A second reagent arm
123 can be included to provide a second reagent to the sample
vessel.
[0028] The sample tube 108 located on the transporter 106 is then
moved to a location near the immunoassay tester 104, FIG. 1C. The
immunoassay tester is similar in operation to the clinical
chemistry tester in that a test sample from the sample tube is
aspirated using sample probe 114 of sample probe arm 112. The
sample arm then moves to a sample vessel (not shown) and deposits
the aspirated sample. After the sample has been discharged from the
probe, the arm moves to a wash station (not shown) where the probe
is washed. The sample vessel is moved to a location where a reagent
is added to the sample by a reagent probe arm 115. The reagent arm
is movable between a reagent location, the sample vessel and the
wash station. The sample vessel may receive additional reagents and
is then subjected to testing, as know to those skilled in the art.
It is clear that sample carryover, or contamination, can occur if
the sample probes are not cleaned between aspirations of different
test samples.
[0029] FIG. 2 illustrates an example probe arm 110. The arm
includes a probe 114 that can be moved about a horizontal arc and
in a vertical direction. The probe has a hollow center that allows
aspiration of a fluid and the subsequent introduction of a wash
fluid. The mechanics of the probe arm are not described in detail
herein, but are generally know to those skilled in the art. For
purposes of understanding the invention, the arm is controllable to
regulate the amount of sample aspirated and the amount and duration
of wash fluid that flows through the probe.
[0030] Referring to FIG. 3, a cross-section view of a probe 114 and
wash cup 126 are illustrated. The size and shape of the probe and
wash cup are illustrative only and not intended to reflect actual
designs or sizes. Those skilled in the art with the benefit of the
present description will appreciate that the probe and wash cup
design can vary without departing from the present invention. The
probe is substantially tube-shaped and includes an exterior surface
132 and an interior surface 130. An interior wash dispenser 136, or
nozzle, is located to discharge a wash fluid into the interior
region of the probe. During a wash operation, the probe is
vertically positioned in the wash cup. The wash cup includes one or
more exterior wash dispensers 138, or nozzles, positioned to spray
a wash fluid toward a center region of the cup and onto the
exterior of the probe.
[0031] The wash fluid pumped through the probe and on its exterior
is the same fluid and depends upon the material that is to be
removed from the probe. The wash fluid can be located in a common
reservoir 140 and pumped to the nozzles using separate pumps 142
and 144. Alternately, a single pump and controllable valves can be
used to pump the wash fluid to the nozzles. The present invention
is not limited to a specific pump design, provided the termination
of the internal fluid and the external fluid can be separately
controlled by pump(s) controller 150. The term `pump` is intended
to include any mechanism that allows for controlled movement of a
liquid, such as the wash fluid.
[0032] As explained above, the probe needs to be sufficiently
cleaned between sample aspirations to reduce sample carryover. The
sample carryover can be a test sample or reagent depending upon the
probe. The internal wash is terminated prior to terminating the
external wash. This termination overlap significantly reduces
sample carryover and allows clinical chemistry testers to meet
restrictive specifications of immunoassay testers. One example wash
for chemistry sampling volume below a predetermined threshold (such
as 15 .mu.L or less) includes a one second external sample probe
wash that ends 100 ms after the internal sample probe wash. The
external wash can begin prior to the internal wash without
departing from the present invention.
[0033] The present invention is not limited to an integrated
clinical chemistry/immunoassay tester, and other analytical systems
can utilize the relationship of between-sample carryover
performance to improve sample wash parameters. This includes other
clinical chemistry and immunoassay systems as well as hematology
and other methodologies. The wash method can also be used utilized
for reagent carryover washing, sample pretreatment instrumentation,
and with laboratory automation systems.
CONCLUSION
[0034] A clinical tester has been described that includes a probe
to aspirate a fluid. The probe is washed between aspirations to
reduce carryover. The wash operation includes both an internal and
an external wash, where the internal wash operation is terminated
prior to terminating the external wash. In one embodiment, the
probe wash can be implemented on an integrated clinical
chemistry/immunoassay tester.
[0035] Although specific embodiments have been illustrated and
described herein, it will be appreciated by those of ordinary skill
in the art that any arrangement, which is calculated to achieve the
same purpose, may be substituted for the specific embodiment shown.
This application is intended to cover any adaptations or variations
of the present invention. Therefore, it is manifestly intended that
this invention be limited only by the claims and the equivalents
thereof.
* * * * *