USRE33858E - Apparatus for measuring a chemical entity in a liquid - Google Patents
Apparatus for measuring a chemical entity in a liquid Download PDFInfo
- Publication number
- USRE33858E USRE33858E US07/471,540 US47154090A USRE33858E US RE33858 E USRE33858 E US RE33858E US 47154090 A US47154090 A US 47154090A US RE33858 E USRE33858 E US RE33858E
- Authority
- US
- United States
- Prior art keywords
- module
- flow passage
- sample
- reagent
- iaddend
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 239000007788 liquid Substances 0.000 title claims abstract description 20
- 150000005829 chemical entities Chemical class 0.000 title claims abstract description 17
- 239000003153 chemical reaction reagent Substances 0.000 claims description 34
- 239000012530 fluid Substances 0.000 claims description 9
- 239000002699 waste material Substances 0.000 claims description 9
- 238000011144 upstream manufacturing Methods 0.000 claims description 5
- 239000000203 mixture Substances 0.000 claims description 3
- 239000012088 reference solution Substances 0.000 claims description 2
- 238000011010 flushing procedure Methods 0.000 claims 6
- 238000005259 measurement Methods 0.000 description 13
- 210000004027 cell Anatomy 0.000 description 9
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 5
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 4
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 4
- 150000002500 ions Chemical class 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 239000011591 potassium Substances 0.000 description 4
- FKNQFGJONOIPTF-UHFFFAOYSA-N Sodium cation Chemical compound [Na+] FKNQFGJONOIPTF-UHFFFAOYSA-N 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- -1 ions Chemical class 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 229910001414 potassium ion Inorganic materials 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910001415 sodium ion Inorganic materials 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- NPYPAHLBTDXSSS-UHFFFAOYSA-N Potassium ion Chemical compound [K+] NPYPAHLBTDXSSS-UHFFFAOYSA-N 0.000 description 2
- 229910021607 Silver chloride Inorganic materials 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 210000002445 nipple Anatomy 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
- 239000004800 polyvinyl chloride Substances 0.000 description 2
- 239000001103 potassium chloride Substances 0.000 description 2
- 235000011164 potassium chloride Nutrition 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 229910052709 silver Inorganic materials 0.000 description 2
- 239000004332 silver Substances 0.000 description 2
- HKZLPVFGJNLROG-UHFFFAOYSA-M silver monochloride Chemical compound [Cl-].[Ag+] HKZLPVFGJNLROG-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M sodium chloride Inorganic materials [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 210000002700 urine Anatomy 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 239000004809 Teflon Substances 0.000 description 1
- 229920006362 Teflon® Polymers 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 230000023402 cell communication Effects 0.000 description 1
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 239000000645 desinfectant Substances 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 239000008151 electrolyte solution Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 239000003295 industrial effluent Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 230000002572 peristaltic effect Effects 0.000 description 1
- 229920000915 polyvinyl chloride Polymers 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 229920002379 silicone rubber Polymers 0.000 description 1
- 239000004945 silicone rubber Substances 0.000 description 1
- 239000012086 standard solution Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
Images
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/08—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a stream of discrete samples flowing along a tube system, e.g. flow injection analysis
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
- G01N35/1095—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices for supplying the samples to flow-through analysers
- G01N35/1097—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices for supplying the samples to flow-through analysers characterised by the valves
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N2035/00178—Special arrangements of analysers
- G01N2035/00326—Analysers with modular structure
Definitions
- 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 2 ; and organic compounds, e.g., glucose, in liquid samples such as blood, urine, and liquids related to industrial processes.
- ions e.g., potassium, sodium, and chloride
- gases e.g., O 2
- organic compounds e.g., glucose
- 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.
- the senor 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.
- a predetermined number of tests e.g., sodium and potassium measurements on 100 whole blood or serum samples.
- the user e.g., a physician using the apparatus in his office
- 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.
- 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.
- 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.
- 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° 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.
- 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.
- 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.
- 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 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).
- each liquid after is has been analyzed, is ejected to waste chamber 26.
- 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.
- 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.
- 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.
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.
Description
This application is a continuation of Ser. No. 695,100 filed Jan. 25, 1985, now abandoned.
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., O2 ; 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.
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.
The drawings will first briefly be described.
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.
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.
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.
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° Geneva mechanism 76, connected to the valves via valve shafts 54.
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.
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).
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 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.
Claims (9)
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.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US07/471,540 USRE33858E (en) | 1985-01-25 | 1990-01-29 | Apparatus for measuring a chemical entity in a liquid |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US69510085A | 1985-01-25 | 1985-01-25 | |
US07/041,650 US4726929A (en) | 1985-01-25 | 1987-04-21 | Apparatus for measuring a chemical entity in a liquid |
US07/471,540 USRE33858E (en) | 1985-01-25 | 1990-01-29 | Apparatus for measuring a chemical entity in a liquid |
Related Parent Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US69510085A Continuation | 1985-01-25 | 1985-01-25 | |
US07/041,650 Reissue US4726929A (en) | 1985-01-25 | 1987-04-21 | Apparatus for measuring a chemical entity in a liquid |
Publications (1)
Publication Number | Publication Date |
---|---|
USRE33858E true USRE33858E (en) | 1992-03-24 |
Family
ID=43339820
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US07/471,540 Expired - Lifetime USRE33858E (en) | 1985-01-25 | 1990-01-29 | Apparatus for measuring a chemical entity in a liquid |
Country Status (1)
Country | Link |
---|---|
US (1) | USRE33858E (en) |
Cited By (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6398956B1 (en) | 1999-05-28 | 2002-06-04 | Bio/Data Corporation | Method and apparatus for directly sampling a fluid for microfiltration |
US20040096358A1 (en) * | 2002-11-14 | 2004-05-20 | Gert Blankenstein | Device for the stepwise transport of liquid utilizing capillary forces |
US20060060531A1 (en) * | 1999-05-28 | 2006-03-23 | Bio/Data Corporation | Method and apparatus for directly sampling a fluid for microfiltration |
US9623415B2 (en) | 2014-12-31 | 2017-04-18 | Click Diagnostics, Inc. | Devices and methods for molecular diagnostic testing |
USD800331S1 (en) | 2016-06-29 | 2017-10-17 | Click Diagnostics, Inc. | Molecular diagnostic device |
USD800913S1 (en) | 2016-06-30 | 2017-10-24 | Click Diagnostics, Inc. | Detection window for molecular diagnostic device |
USD800914S1 (en) | 2016-06-30 | 2017-10-24 | Click Diagnostics, Inc. | Status indicator for molecular diagnostic device |
US10195610B2 (en) | 2014-03-10 | 2019-02-05 | Click Diagnostics, Inc. | Cartridge-based thermocycler |
US10675623B2 (en) | 2016-06-29 | 2020-06-09 | Visby Medical, Inc. | Devices and methods for the detection of molecules using a flow cell |
US11162130B2 (en) | 2017-11-09 | 2021-11-02 | Visby Medical, Inc. | Portable molecular diagnostic device and methods for the detection of target viruses |
US11193119B2 (en) | 2016-05-11 | 2021-12-07 | Visby Medical, Inc. | Devices and methods for nucleic acid extraction |
Citations (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3554648A (en) * | 1967-12-29 | 1971-01-12 | Sargent Welch Scientific Co | Combination teaching aid and modular instrumental analysis system and components therefor |
US3842679A (en) * | 1973-03-05 | 1974-10-22 | Varian Associates | Automatic sampler apparatus of modular construction |
US3912455A (en) * | 1971-01-20 | 1975-10-14 | Lichtenstein Eric Stefan | Apparatus for clinical laboratory sample collection and automatic sample processing |
USRE28801E (en) * | 1972-09-20 | 1976-05-04 | Akro-Medic Engineering, Inc. | Apparatus for evaluation of biological fluid |
US4006412A (en) * | 1974-10-29 | 1977-02-01 | The United States Of America As Represented By The Secretary Of The Navy | Digital display system circuit |
US4119406A (en) * | 1976-05-06 | 1978-10-10 | Miles Laboratories, Inc. | Calibration apparatus |
US4169125A (en) * | 1977-04-14 | 1979-09-25 | Baxter Travenol Laboratories, Inc. | Modular chemical analysis system |
US4224033A (en) * | 1977-02-16 | 1980-09-23 | Bifok Ab | Programmable, continuous flow analyzer |
US4338280A (en) * | 1981-04-02 | 1982-07-06 | Instrumentation Laboratory Inc. | Fluid sampling |
US4390499A (en) * | 1981-08-13 | 1983-06-28 | International Business Machines Corporation | Chemical analysis system including a test package and rotor combination |
US4499053A (en) * | 1982-06-10 | 1985-02-12 | Instrumentation Laboratory Inc. | Fluid sampling |
-
1990
- 1990-01-29 US US07/471,540 patent/USRE33858E/en not_active Expired - Lifetime
Patent Citations (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3554648A (en) * | 1967-12-29 | 1971-01-12 | Sargent Welch Scientific Co | Combination teaching aid and modular instrumental analysis system and components therefor |
US3912455A (en) * | 1971-01-20 | 1975-10-14 | Lichtenstein Eric Stefan | Apparatus for clinical laboratory sample collection and automatic sample processing |
USRE28801E (en) * | 1972-09-20 | 1976-05-04 | Akro-Medic Engineering, Inc. | Apparatus for evaluation of biological fluid |
US3842679A (en) * | 1973-03-05 | 1974-10-22 | Varian Associates | Automatic sampler apparatus of modular construction |
US4006412A (en) * | 1974-10-29 | 1977-02-01 | The United States Of America As Represented By The Secretary Of The Navy | Digital display system circuit |
US4119406A (en) * | 1976-05-06 | 1978-10-10 | Miles Laboratories, Inc. | Calibration apparatus |
US4224033A (en) * | 1977-02-16 | 1980-09-23 | Bifok Ab | Programmable, continuous flow analyzer |
US4169125A (en) * | 1977-04-14 | 1979-09-25 | Baxter Travenol Laboratories, Inc. | Modular chemical analysis system |
US4338280A (en) * | 1981-04-02 | 1982-07-06 | Instrumentation Laboratory Inc. | Fluid sampling |
US4390499A (en) * | 1981-08-13 | 1983-06-28 | International Business Machines Corporation | Chemical analysis system including a test package and rotor combination |
US4499053A (en) * | 1982-06-10 | 1985-02-12 | Instrumentation Laboratory Inc. | Fluid sampling |
Non-Patent Citations (2)
Title |
---|
Orion Model 1020 Na/K Brochure; Orion Research, Cambridge, Mass., ©1982. |
Orion Model 1020 Na/K Brochure; Orion Research, Cambridge, Mass., 1982. * |
Cited By (28)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6398956B1 (en) | 1999-05-28 | 2002-06-04 | Bio/Data Corporation | Method and apparatus for directly sampling a fluid for microfiltration |
US20020084215A1 (en) * | 1999-05-28 | 2002-07-04 | Bio/Data Corporation | Method and apparatus for directly sampling a fluid for microfiltration |
US6740240B2 (en) | 1999-05-28 | 2004-05-25 | Bio/Data Corporation | Method and apparatus for directly sampling a fluid for microfiltration |
US20040217059A1 (en) * | 1999-05-28 | 2004-11-04 | Bio/Data Corporation | Method and apparatus for directly sampling a fluid for microfiltration |
US6926834B2 (en) | 1999-05-28 | 2005-08-09 | Bio/Data Corporation | Method and apparatus for directly sampling a fluid for microfiltration |
US20060060531A1 (en) * | 1999-05-28 | 2006-03-23 | Bio/Data Corporation | Method and apparatus for directly sampling a fluid for microfiltration |
US7288195B2 (en) | 1999-05-28 | 2007-10-30 | Bio/Data Corporation | Method and apparatus for directly sampling a fluid for microfiltration |
US20040096358A1 (en) * | 2002-11-14 | 2004-05-20 | Gert Blankenstein | Device for the stepwise transport of liquid utilizing capillary forces |
US7316802B2 (en) * | 2002-11-14 | 2008-01-08 | Boehringer Ingelheim Microparts Gmbh | Device for the stepwise transport of liquid utilizing capillary forces |
US10960399B2 (en) | 2014-03-10 | 2021-03-30 | Visby Medical, Inc. | Cartridge-based thermocycler |
US10195610B2 (en) | 2014-03-10 | 2019-02-05 | Click Diagnostics, Inc. | Cartridge-based thermocycler |
US10112197B2 (en) | 2014-12-31 | 2018-10-30 | Click Diagnostics, Inc. | Devices and methods for molecular diagnostic testing |
US10525469B2 (en) | 2014-12-31 | 2020-01-07 | Visby Medical, Inc. | Devices and methods for molecular diagnostic testing |
US10052629B2 (en) | 2014-12-31 | 2018-08-21 | Click Diagnostics, Inc. | Devices and methods for molecular diagnostic testing |
US11273443B2 (en) | 2014-12-31 | 2022-03-15 | Visby Medical, Inc. | Devices and methods for molecular diagnostic testing |
US10112196B2 (en) | 2014-12-31 | 2018-10-30 | Click Diagnostics, Inc. | Devices and methods for molecular diagnostic testing |
US10124334B2 (en) | 2014-12-31 | 2018-11-13 | Click Diagnostics, Inc. | Devices and methods for molecular diagnostic testing |
US11167285B2 (en) | 2014-12-31 | 2021-11-09 | Visby Medical, Inc. | Devices and methods for molecular diagnostic testing |
US10279346B2 (en) | 2014-12-31 | 2019-05-07 | Click Diagnostics, Inc. | Devices and methods for molecular diagnostic testing |
US10456783B2 (en) | 2014-12-31 | 2019-10-29 | Click Diagnostics, Inc. | Devices and methods for molecular diagnostic testing |
US9623415B2 (en) | 2014-12-31 | 2017-04-18 | Click Diagnostics, Inc. | Devices and methods for molecular diagnostic testing |
US11193119B2 (en) | 2016-05-11 | 2021-12-07 | Visby Medical, Inc. | Devices and methods for nucleic acid extraction |
US10675623B2 (en) | 2016-06-29 | 2020-06-09 | Visby Medical, Inc. | Devices and methods for the detection of molecules using a flow cell |
USD800331S1 (en) | 2016-06-29 | 2017-10-17 | Click Diagnostics, Inc. | Molecular diagnostic device |
USD800914S1 (en) | 2016-06-30 | 2017-10-24 | Click Diagnostics, Inc. | Status indicator for molecular diagnostic device |
USD800913S1 (en) | 2016-06-30 | 2017-10-24 | Click Diagnostics, Inc. | Detection window for molecular diagnostic device |
US11162130B2 (en) | 2017-11-09 | 2021-11-02 | Visby Medical, Inc. | Portable molecular diagnostic device and methods for the detection of target viruses |
US11168354B2 (en) | 2017-11-09 | 2021-11-09 | Visby Medical, Inc. | Portable molecular diagnostic device and methods for the detection of target viruses |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US4726929A (en) | Apparatus for measuring a chemical entity in a liquid | |
EP0179129B1 (en) | Self-calibrating single-use sensing device for clinical chemistry analyzer | |
EP0098550B1 (en) | Method and apparatus for conducting flow analysis | |
US4654127A (en) | Self-calibrating single-use sensing device for clinical chemistry and method of use | |
EP2147307B1 (en) | A sensor assembly for body fluids | |
EP1942332B1 (en) | Measuring device, measuring apparatus and method of measuring | |
USRE33858E (en) | Apparatus for measuring a chemical entity in a liquid | |
US20030019748A1 (en) | Method and apparatus for stripping voltammetric and potent iometric detection and measurement of contamination in liquids | |
US4490235A (en) | Electrochemical cell provided with selective electrodes and at least one chemical reactor, for indirect measurement of clinical-chemical parameters | |
AU682522B2 (en) | Analysis system and components | |
JP4554171B2 (en) | Analytical test cartridge and method | |
US6719888B1 (en) | Reference electrode assembly | |
JPS5999248A (en) | Blood analyzer | |
KR100943114B1 (en) | Cartridge-type electrochemical analysis apparatus and method | |
Arquint et al. | Organic membranes for miniaturized electrochemical sensors: Fabrication of a combined pO2, pCO2 and pH sensor | |
US20220280937A1 (en) | Arrangement for analyzing a liquid sample | |
US4964971A (en) | Liquid analyzer | |
CN217688681U (en) | Sample analyzer | |
CN220064066U (en) | Biochemical analyzer | |
Ehlert et al. | Automatic sensor system for water analysis | |
JPS61176857A (en) | Method and instrument for analyzing specimen | |
HRP20030936A2 (en) | Multiple sensor for simultaneous measurement (activation) of electrolytes concentration in serum, plasma and blood samples | |
JPH01262472A (en) | Automatic chemical analyzer |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
FEPP | Fee payment procedure |
Free format text: PAYOR NUMBER ASSIGNED (ORIGINAL EVENT CODE: ASPN); ENTITY STATUS OF PATENT OWNER: LARGE ENTITY |
|
FEPP | Fee payment procedure |
Free format text: PAYER NUMBER DE-ASSIGNED (ORIGINAL EVENT CODE: RMPN); ENTITY STATUS OF PATENT OWNER: LARGE ENTITY Free format text: PAYOR NUMBER ASSIGNED (ORIGINAL EVENT CODE: ASPN); ENTITY STATUS OF PATENT OWNER: LARGE ENTITY |
|
FPAY | Fee payment |
Year of fee payment: 8 |