U.S. patent number RE33,858 [Application Number 07/471,540] was granted by the patent office on 1992-03-24 for apparatus for measuring a chemical entity in a liquid.
This patent grant is currently assigned to Mallinckrodt Sensor Systems Inc.. Invention is credited to Andrian Gropper, Richard Sidell.
United States Patent |
RE33,858 |
Gropper , et al. |
March 24, 1992 |
Apparatus for measuring a chemical entity in a liquid
Abstract
Apparatus for measuring or detecting a chemical entity in a
liquid sample, the apparatus including a first module operationally
connected to a second module, the first module having a flow
passage for the sample, the flow passage including a sensor for
measuring or detecting the chemical entity and .Iadd.a
.Iaddend.pump .[.means.]. for advancing the sample along the flow
passage, the second module including .[.means.]. .Iadd.an actuator
.Iaddend.for actuating the pump means, and the second module being
connected to the first module via .[.connecting means.]. .Iadd.a
connector .Iaddend.permitting disconnection of the first and second
modules and connection of a replacement first module to the second
module.
Inventors: |
Gropper; Andrian (Cambridge,
MA), Sidell; Richard (Needham, MA) |
Assignee: |
Mallinckrodt Sensor Systems
Inc. (Ann Arbor, MI)
|
Family
ID: |
43339820 |
Appl.
No.: |
07/471,540 |
Filed: |
January 29, 1990 |
Related U.S. Patent Documents
|
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
Issue Date |
|
|
695100 |
Jan 25, 1985 |
|
|
|
Reissue of: |
041650 |
Apr 21, 1987 |
04726929 |
Feb 23, 1988 |
|
|
Current U.S.
Class: |
422/68.1;
356/244; 356/246; 422/547; 422/82; 422/82.04 |
Current CPC
Class: |
G01N
35/08 (20130101); G01N 35/1097 (20130101); G01N
2035/00326 (20130101) |
Current International
Class: |
G01N
27/28 (20060101); G01N 35/08 (20060101); G01N
001/10 () |
Field of
Search: |
;422/68.1,81,82,100,102,82.04 ;356/244,246 |
References Cited
[Referenced By]
U.S. Patent Documents
Other References
Orion Model 1020 Na/K Brochure; Orion Research, Cambridge, Mass.,
.COPYRGT.1982..
|
Primary Examiner: Kummert; Lynn
Attorney, Agent or Firm: Krass & Young
Parent Case Text
This application is a continuation of Ser. No. 695,100 filed Jan.
25, 1985, now abandoned.
Claims
What is claimed is:
1. Apparatus for measuring or detecting a chemical entity in a
liquid sample, said apparatus comprising a first module
operationally connected to a second module,
said first module comprising a flow passage for receiving at least
one liquid sample and having reagent containing means, of
sufficient size with sufficient reagent to .[.mix with.].
.Iadd.analyze .Iaddend.a plurality of samples entering said flow
passage to allow for successive analysis of a .[.plurlaity.].
.Iadd.plurality .Iaddend.of samples, and having flushing fluid
containing means said flow passage including a sensor section
including sensor means for contacting fluid comprising a liquid
sample .[.and.]. .Iadd.or .Iaddend.reagent to measure or detect a
chemical entity of the fluid while establishing a noncontaminating
relationship with said second module and said first module
including pump means for advancing the sample along said flow
passage and actuating said flushing fluid containing means, thereby
flushing said first module between analysis of successive
samples,
said second module comprising means for actuating said pump
means,
said second module being connected to said first module via
connecting means permitting disconnection of said first module from
said second module and connection of a replacement first module to
said second module,
and wherein .Iadd.said .Iaddend.first module is in the form of a
sealed disposable cartridge.
2. The apparatus of claim 1 wherein said sensor means of said first
module comprises a plurality of different sensors for measuring a
plurality of different chemical entities in a sample.
3. The apparatus of claim 1 wherein said pump means is located
downstream from said sensor section.
4. The apparatus of claim 1 wherein said first module includes,
downstream from said sensor section, a waste chamber for holding a
sample after said chemical entity in the sample has been detected
or measured.
5. The apparatus of claim 1 wherein said apparatus further
comprises at least one reference chamber containing sufficient
reference solution for analysis of a plurality of samples.
6. The apparatus of claim 1 wherein said flow passage of said first
module includes, upstream from said sensor section, a sample inlet
port for introducing the liquid sample into said first module.
7. The apparatus of claim 6 wherein said flow passage includes,
downstream from said sample inlet port and upstream from said
sensor section, a selector valve for controlling the intake of a
sample into said flow passage, and wherein said second module
includes means for actuating said selector valve.
8. The apparatus of claim 7 wherein said first module further
comprises a holding chamber for holding a calibrating reagent, said
holding chamber being connected to said flow passage, and passage
of said calibrating reagent into said flow passage being controlled
by said selector valve.
9. A replaceable module in the form of a disposable cartridge for
use in apparatus for measuring or detecting a chemical entity in a
liquid sample that establishes a non-contaminating relationship
with said apparatus, said replaceable module comprising a flow
passage for receiving at least one liquid sample, and having
reagent containing means of sufficient size with sufficient reagent
to .[.mix with.]. .Iadd.analyze .Iaddend.a plurality of samples
entering said flow passage to allow for successive analysis of a
plurality of samples, and having a flushing fluid containing means,
and wherein said flow passage includes a sensor section including
sensor means for contacting fluid comprising a liquid sample
.[.and.]. .Iadd.or a .Iaddend.reagent, allowing for measuring or
detecting a chemical entity of the fluid, said module including
pump means for advancing the sample along said flow passage and
actuating said flushing fluid containing means, thereby flushing
said module between analysis of successive samples.
Description
BACKGROUND OF THE INVENTION
This invention relates to the measurement of chemical entities in
liquid samples.
A wide variety of analytical systems are available for measuring
chemical entities such as ions, e.g., potassium, sodium, and
chloride; gases, e.g., O.sub.2 ; and organic compounds, e.g.,
glucose, in liquid samples such as blood, urine, and liquids
related to industrial processes. Such systems contain components
which from time to time require maintenance or replacement.
SUMMARY OF THE INVENTION
In general, the invention features apparatus for measuring or
detecting a chemical entity in a liquid sample, including a first
module operationally connected to a second module, the first module
having a flow passage for the sample including a sensor for
measuring or detecting the chemical entity and pump means for
advancing the sample along the flow passage, and the second module
having means for actuating the pump means, the two modules being
connected via means permitting disconnection and replacement of the
first module.
In preferred embodiments, the sensor is capable of successively
analyzing a plurality of samples; the first module includes a
plurality of different sensors for measuring a plurality of
different chemical entities in the sample; the pump means is
located downstream from the sensor; and the first module further
includes a waste chamber for holding the sample after the chemical
entity has been measured, and a holding chamber for a calibrating
reagent, whose passage into the flow passage is controlled by a
selector valve which also controls intake of the sample into the
flow passage, and which is actuated by means contained in the
second module.
The flow-through apparatus of the invention provides all of the
components which come into contact with the sample--the flow
passage, sensors, and pump--as well as the depletable calibration
reagent, in a sealed, disposable cartridge which, after it has been
used to carry out a predetermined number of tests (e.g., sodium and
potassium measurements on 100 whole blood or serum samples), is
disposed of in its entirety and replaced. The user (e.g., a
physician using the apparatus in his office) does not need to learn
how to maintain the electrodes or the pump, or keep reagents on
hand to refill reagent containers (a procedure which also carries
with it the possibility of the introduction of contaminants, or the
refilling of a container with the wrong reagent.)
Another advantage of the apparatus of the invention is that the
disposable cartridge obviates expensive, time-consuming, and
potentially contaminant-introducing preventive maintenance involved
in the cleaning and/or replacement not just of reagents but also of
the sensors, tubing, and other flow path elements, which would
otherwise need to be kept in stock to be available when needed, and
which would require, for servicing, the ready availability of
trained service personnel, to both recognize the need for, and
provide, such servicing.
An additional advantage of the apparatus of the invention is that
the short, nearly horizontal flow path of the disposable cartridge
prevents the development of a fully laminar flow path, which could
otherwise result in measurement errors.
Other features and advantages of the invention will be apparent
from the following description of the preferred embodiment thereof,
and from the claims.
DESCRIPTION OF THE PREFERRED EMBODIMENT
The drawings will first briefly be described.
DRAWINGS
FIG. 1 is a diagrammatic representation of measurement apparatus of
the invention;
FIG. 2 is a plan view of the top and bottom portions of apparatus
of the invention;
FIG. 3 is a bottom plan view of a portion of the apparatus of FIG.
2;
FIGS. 4 and 5 are side sectional views of portions of said
apparatus;
FIG. 6 is a perspective view of a portion of said apparatus;
FIG. 7 is a sectional view taken at 7--7 of FIG. 6;
FIG. 8 is a perspective view of an electrode assembly of said
apparatus.
STRUCTURE
Referring to FIG. 1, analyzing apparatus 10 includes first module
12, connected to second module 14 such that module 12, a disposable
cartridge, can be replaced periodically.
First module 12 contains a sample flow passage including, beginning
upstream, sample inlet port 18; photosensor 49; flow cell 22,
containing electrodes 24; and waste chamber 26. Reagent holding
chambers 28 and 29 communicate with rotary selector valve 20 via
passages 30 and 31. Flow cell 22 also includes, downstream from
electrodes 24, rotary valve 32 which communicates with pump 34 via
passage 39, and with reference chamber 78 via passage 37.
Second module 14 includes valve motor 36, computer 38 associated
with display screen 40, and pump motor 42. Valve motor 36 is
operatively connected to valves 20 and 32, via activator shafts 54.
Pump motor 42 is operatively connected to pump 34 via pump cam 77.
Electrodes 24 and reference chamber 78 are connected to computer 38
via electrical connections 48, and motors 36 and 42 are connected
to computer 38 via electrical connections 50 and 52,
respectively.
Referring now to FIG. 2, there is shown apparatus 10 taken apart,
as when module 12 is to be replaced; the top portion of module 14
(containing the motors and computer) is shown in plan topside down,
and module 12 and the bottom portion of module 14 (serving as a
holder for module 12) are shown in plan. Module 12 fits into the
bottom portion of module 14 such that the flat surface of each is
flush with the other. The top portion of module 14 fits onto the
bottom cartridge holder portion via snap connector posts 17, which
mate with holes 15. Valve shafts 54 mate with valves 20 and 32.
Module 12 also includes vent 13 and six electrical connections 19,
which meet pogo pin connections 100 in the top of module 14. As
shown in FIG. 2, two of the connections are connected to contact
points 82 from the two electrodes of the electrode assembly (FIG.
8) via wires 33; one to silver/silver chloride wire 43 from
reference chamber 78; and three to the connection 47 to photosensor
49 at the entrance to flow passage 18. Module 12 further includes
reagent inlet tubes 56 and 58 from reagent chambers 28 and 29,
respectively; waste tube 64, leading to waste chamber 26 (which
contains a disinfectant); reference tube 65 leading to reference
chamber 78; and pump tube 45, leading to pump 34 (FIG. 1). Four
vent tubes 51 connect chambers 28, 29, 26, and 78 with vent 13.
Also shown is diaphragm 71 of pump 34. Slot 21 is large enough to
permit the finger of the user to reach into module 14 to remove
module 12 and then insert its identical replacement.
FIG. 3 is a bottom plan view of module 12, showing reagent chambers
28 and 29, reference liquid chamber 78, and waste chamber 26,
surrounding the other three chambers.
FIG. 4 is a side sectional view of module 12, showing the
positioning of the chambers below the remainder of the module.
FIG. 5, a side sectional view of apparatus 10 above the level of
the reagent chambers and through the center of the flow passage,
illustrates the relationship between motors 36 and 42 of module 14,
and flow cell 22 and the remaining portion of the flow passage of
module 12. Motor 36 drives Teflon and plastic rotary valves 20 and
32 via 3-poition, 45.degree. Geneva mechanism 76, connected to the
valves via valve shafts 54.
Motor 42 is connected via pump cam 77 to pump 34, which is made up
of shaft 73, plunger 72, flexible diaphragm 71, and pump chamber
70; shaft 73 and plunger 72 are components of module 14, while
diaphragm 71 and chamber 70 are components of module 12. Motors 42
and 36 are both Cannot PF55 series stepping motors. Flow cell 22,
which is cast of flexible silicone rubber, makes nipple connection
39 with the remainder of module 12, at the point of continuation of
the flow passage.
FIG. 6 illustrates flow cell 22 and its connection to the remainder
of apparatus 10. Slot 41 holds electrode assembly 80 (FIG. 8). All
tubes mate with openings in flow cell 22 via nipple connections.
Opening 63 is adapted to receive glass capillary tube 67.
FIG. 7, taken at 7--7 of FIG. 6, shows passages of flow cell 22,
including the upstream (19) and downstream (39) portions of the
flow passage, reagent passages 30 and 31, waste passage 35, and
reference passage 37.
Referring to FIG. 8, molded polyvinylchloride (PVC) electrode
assembly 80 includes electrical connection points 82, connected to
silver/silver chloride electrode wires 81 in the electrolyte
solution of each electrode; two recessed, electrolyte-containing
chambers 84; covered with flat, ultrasonically welded plastic
plates 86; flow passage 88, including a sensor section including
inlet and outlet ports 90 and 92, respectively; and integrated cast
PVC, potassium ion selective and sodium ion selective membranes 94
flush with the remainder of the flow passage. The potassium ion
selective membrane was made generally as described in Mikrochim,
Acta (1980) Vol. II, page 309, and the sodium ion selective
membrane was made generally as described in Auber et al. (1983)
Clin. Chem. 29(8), 1508.
OPERATION
Referring to the Figures, to analyze a blood sample for potassium
and sodium concentration, the sample is placed in capillary tube
67, which is inserted into the apparatus, triggering photosensor
49, which activates computer 38, which has been programmed to
activate motors 36 and 42 to automatically take the sample through
one measuring cycle, and to receive and process generated data. The
computer and its software are not included in the present
invention. In the illustrated embodiment, they are shown contained
in module 14; they could just as well be in a separate module
electrically connected to module 14.
The potassium and sodium ion concentrations of calibration reagent
28, sample, and calibration reagent 29, are measured sequentially.
Each liquid is drawn into the flow path to contact the electrodes
by the action of valves 20 and 32, and of pump 34. Motor 36,
through Geneva mechanism 76, drives both valve 20, the position of
which determines whether the sample, calibration reagent 28, or
calibration reagent 29 enters the flow cell, and valve 32, the
position of which determines the flow cell's communication with the
pump, the reference chamber, and the waste chamber. The pump
determines fluid volume in the flow cell, and moves up and down
mechanically independently of the valves.
The electrochemical potentials of the sample and the calibration
reagents are determined with reference to the reference liquid
which, prior to each measurement, meets the liquid being analyzed
in the downstream region 39 of the flow passage to create a liquid
junction. The generated signals (electrical potentials) are then
amplified and digitalized via an analog/digital converter; the
activity of each ion is automatically calculated using the Nicolsky
equation.
The first step in the process is a calibration analysis of the
calibration reagent 28 remaining in the flow passage from the
previous measurement; this is an isotonic sodium and potassium
chloride reagent. After this measurement has been made, the sample
fills the flow passage and is analyzed. Next, sodium and potassium
chloride calibration reagent 29 enters and is analyzed, and then
additional calibration reagent 28 enters and is analyzed, and
remains for the start of the next cycle.
The measurements of the two calibration reagents serve to calibrate
the electrodes, to act as a check on instrument functions, and to
flush the system between samples. The salt solutions in chambers
28, 29, and 78 are all standard solutions used for these purposes
by persons of ordinary skill in this field; their composition and
method of preparation are given in Osswalt et al. page 74, in
Lubbers et al. (1981).
PROGRESS IN ENZYME AND ION SELECTIVE ELECTRODES
(Springer-Verlag).
Each liquid, after is has been analyzed, is ejected to waste
chamber 26. As reagents and reference solution are depleted, air
enters the chamber via vent 13; each chamber (i.e. chambers 26, 28,
29, and 78) is separately vented.
After a predetermined number of samples have been analyzed (when
reagents have been exhausted), the user opens the top of module 14,
reaches into opening 21, lifts out module 12, discards it, drops in
a replacement module 12, and closes the top portion of module 14.
Valve shafts 54 reversibly mate with valves 20 and 32, and
electrical contact points 19 make contact. At this point, the
apparatus is ready for use, with none of the components which
contact the sample having been retained, cleaned, serviced, or
touched by the user.
OTHER EMBODIMENTS
Other embodiments are within the following claims.
For example, the number of measurements made on each sample can be
as low as one, or there can be measurement of considerably more
than two chemical entities. Measurements of different chemical
entities can be carried out at the same point in the flow passage,
as in the above-described embodiment, or sequentially along the
flow passage. Any chemical measurements can be made, using any
chemical sensors; in addition to ion selective electrodes,
measurements can be made using, e.g., pH electrodes, enzyme
electrodes, or antibody/antigen sensors. Any liquid sample can be
analyzed, e.g., urine, cerebrospinal fluid, industrial effluents,
or drinking water. Any pump configuration can be used, e.g.,
peristaltic roller pumps, and the pump means can be located
anywhere in the flow path, e.g., upstream rather than downstream
from the sensor. One, rather than two, calibration reagents, can be
used, and in some instances more than two or no calibration reagent
will be required. The module containing the motors can be of any
suitable configuration, e.g., all one piece, or two hinged parts.
Any other valves, including check, poppet or squeeze valves, can be
used; and any actuating means, e.g., other motors, electromagnetic
actuators such as solenoids, or spring arrangements, can be used.
Each valve and the pump can be driven by its own actuator, or one
actuator can be used to drive all of them.
* * * * *