Non-invasive method of determining residual liquid reagents

Abstract: A method of determining the volume of liquid reagent remaining in a reagent bottle in a chemical analyzer, using a known air pressure to test the volume, or rate of pressure build-up, produced by the air volume remaining in a bottle of known empty volume for such liquid reagent. The tested pressure, or rate of pressure build-up, is compared against the pressure or rate produced by such bottle when empty, or such bottle when full. Pressure readings are taken preferably before the end-point pressure is achieved.

Description: The invention relates to a method of determining non-invasively, the amount of liquid reagent remaining in a reagent bottle in a chemical analyzer. It is known that bottles of reagent liquids in analyzers can be checked for their contents by invasive methods, or those requiring operator involvement for visual inspection. However, both of these are time consuming, and the latter is labor intensive. Therefore there has been a need prior to this invention to provide an automatic, non-intrusive method for determining the level of liquid reagent in such bottles. It has been known to utilize air pressure to inject a test bearing to determine if enough grease is present. As described in US-A-4,875,366, for example, this is done by injecting a controlled air pressure into a "control" bearing having just "enough" grease, to measure the pressure therein as a standard, and then injecting the controlled pressure into a test bearing with unknown amounts of grease to see how the detected pressure compares to the established standard. However, this is not a field appropriate for clinical analyzers, and in any event the "standard" is always a value with some residual grease remaining. In the case of a reagent bottle, however, the minimum tolerated liquid is zero, to allow a full continuum of pressure to be accurately plotted or calculated. We have provided a solution to the sensing need noted above. More specifically, there is provided a method of determining the volume of an incompressible liquid reagent in a bottle of known volume in a chemical analyzer, by detecting the air volume of the bottle not occupied by the liquid reagent, comprising the steps of a) providing an infinite source of pressurized gas at a fixed known pressure, b) connecting the source first to at least one control bottle having a known volume of liquid reagent so that the pressurized gas is supplied to the control bottle to calibrate the pressure build-up as a function of the known volume, c) connecting the source second to a test bottle of unknown amount of liquid reagent so that the pressurized gas is supplied to the test bottle, d) comparing the pressure build-up of the test bottle with that of the at least one control bottle, the connecting steps of steps b) and c) comprising supplying the pressurized gas at a variable flow rate at the fixed pressure so as to measure the variation in flow rate caused by variations in liquid volume present in the test bottle, the variable flow rate and the infinite source of fixed gas pressure being sufficient, over an extended period of time, to produce a final predetermined end-point pressure that is the same in both the control bottle and the test bottle; and e) generating a signal indicative of the predicted remaining liquid volume in the test bottle from the comparison in step d). Thus it is an advantageous feature of the invention that the remaining amounts of liquid reagent in the analyzer bottle, including substantially none at all, can be automatically and non-intrusively determined. Yet another related advantageous feature of the invention is that the liquid level detection. requires no mechanical motion of sensors into or out of the reagent bottles, thus reducing contamination of analyzer parts and the likelihood of wearing out parts. Other advantageous features will become apparent upon reference to the following "Description of the Preferred Embodiments", when read in light of the attached drawings. Fig. 1 is a plot of pressure over time, illustrating the principle of the invention; and Fig. 2 is a schematic diagram showing apparatus useful in carrying out the invention. What follows is stated in the context of the preferred embodiments, wherein certain preferred apparatus is used to provide pressurized air at a known pressure to reagent bottles, and for reading the resulting pressures, or rate of pressure increase, in the bottles at a preferred time, or the time it takes to reach a fixed pressure, all before end-point is reached. In addition, the invention is useful regardless of such particular apparatus that is used or what gas (air or otherwise) is used, and regardless whether the time at which readings are made is before end-point or not. As used herein, "substantially empty" refers to the condition in which the reagent bottle is for all practical purposes empty, that is,. one in which any residual liquid is insufficient for use by the analyzer. "Substantially full" in a similar manner means, as full as is practical. Referring to Fig. 1, when air pressure is injected into a container, specifically either a reagent bottle or a control bottle, at time t 0 , the pressure within the bottle starts out at a value labeled "P ambient " (shown as P amb ), that is, the pressure otherwise already present. Over time, it builds up, curves 10, 20 and 30, to eventually reach an end-point pressure "P endpoint ", that is the maximum pressure that can be present in either the control bottle(s) or the test bottle for that rate of incoming pressurized air. Before the end-point is reached, after some chosen time T fixed , the pressure detectable above any liquid in the bottle will be some value between P empty and P full , where P empty is a minimum pressure available due to substantially no incompressible liquid reagent being present, and P full is the maximum pressure detectable when the reagent bottle is substantially full of liquid reagent. Any of said bottles with unknown amounts of liquid reagent. produce a P unknown reading at time t fixed , that is some value ΔP above P empty (or below P full ). Hence, the method requires either P empty or P full to be known, and not necessarily both, although the use of both is preferred. (Alternatively, any two conditions between and including P empty and P full can be used as the control, but for most accurate results the two extremes are preferred.) Alternatively, the rate of pressure increase R E or R F , can be plotted and compared with the rate for the unknown, R S , at time t fixed , to differentiate between the conditions. These rates are the slopes of the curves. Preferred is the reading of rates of pressure increase (or absolute pressures) in the time region "A" of Fig. 1, rather than region "B". The reason of course is that as curves 10, 20, or 30 asymptotically approach P endpoint (at times t E1 , t E2 , and t E3 ,), the actual time of intersection of the curve with Pendpoint becomes difficult to determine. The method then involves using an infinite source of incoming air at a fixed known pressure to a) plot or determine pressure values of a variable flow rate (or plot the rate of change of pressure value) for two control bottles, one of which eg is substantially empty, between times t 0 and some time thereafter, for example, t fixed . Curve 10 is for the substantially empty control bottle, and curve 20 for the substantially full one. Then, b) plot or determine the pressure values for curve 30 in a test bottle to determine the value of the air pressure above the liquid reagent, or rate of build-up of pressure, at time t fixed when such bottle contains an unknown amount of liquid reagent. If P unknown produces a ΔP that is approaching zero, for example, no more than 1 psi for a total empty bottle volume of 2 L, then a signal is generated to alert the operator of the analyzer that that particular reagent bottle needs to be replaced. The reason is that such minimal ΔP values represent 100 cc of liquid reagent left in such a volume of bottle. When comparing rates at time t fixed (for example, 1 sec after t 0 ), it is preferred that more than P full and P empty be known in a calibrated look-up table, so that interpolation between known values is minimized. Any conventional apparatus can be utilized, as will be apparent to one skilled, to achieve this method. As an illustrative example, Fig. 2, a chemical analyzer includes one or more liquid reagent bottles 42 (only one being shown). Each of these is sealed to an aspirating line 44 that feeds reagent liquid on demand to the rest of the analyzer, shown in phantom as "40", and at the top 46 of the bottle, an air line 48 which branches at 50 to a pressure sensor such as a pressure transducer 52. The other branch from 50 is connected to one of three ports of a three-way valve 54. A second port of the valve is vented to the atmosphere (not shown) as is conventional, and the third port is connected to an air line 56 that connects with a restrictor valve 58, connected in turn by air line 60 to the outlet of a pressure regulator 62. A compressor 64 is connected to the inlet of regulator 62. All of these pieces of the apparatus are conventional. (The analyzer parts are also conventional, and include a master computer that controls the steps needed to carry out the invention embodiments.) It will be readily apparent that such a system provides an infinite source of fixed air pressure, which when fed into one of the bottles, produces a variable flow rate. That is, the flow rate necessarily varies, depending on the volume of reagent liquid present. Thus, when bottle 42 is to be tested, valve 54 closes the vent to the atmosphere, and opens line 48 to line 56 to allow build-up of pressure in bottle 42. Pressure sensor 52 generates and sends a signal, line 66, to the analyzer so that the resident pressure in bottle 42 is detected at time t fixed . Alternatively, the rate of pressure buildup can be measured at that time. The analyzer has stored in it, the control values obtained by determining such pressure buildup at time t fixed at least when bottle 42 is substantially empty, and/or when bottle 42 is substantially full. Alternatively, intermediate values of a control bottle 42's volume can also be predetermined to more fully calibrate the values between P empty and P full , if such is desired. Yet another preferred use of this method and said apparatus is that, if at time t 1 , the resident pressure P unknown , or rate of pressure build-up is substantially equal to P ambient , or zero respectively, then the analyzer generates an error signal that bottle 42 is "missing". That is, such a signal is possible only if line 48 is emptying out into an infinite volume, that is, the volume present in the absence of bottle 42. The signal generations and comparisons are done of course in one or more microprocessors in analyzer 40 (not shown). The programming needed for such is conventional. As will be readily apparent from Figs. 1 and 2, an alternative approach, instead of reading the variable pressure at fixed time t fixed , is to have the apparatus described above, read the variable time it takes to get to a fixed PRESSURE P fixed . Thus, as shown, the method in such a case, using the apparatus of Fig. 2, reads the time it takes to get to P fixed . The time "t 2 " it takes for the test bottle, when compared to the times "t 1 " for the substantially full control bottle, or "t 3 " for the substantially empty control bottle, is inversely proportional to the amount of liquid reagent remaining in the test bottle.

Claims: A method of determining the volume of an incompressible liquid reagent in a bottle of known volume in a chemical analyzer, by detecting the air volume of the bottle not occupied by the liquid reagent, comprising the steps of a) providing an infinite source of pressurized gas at a fixed known pressure, b) connecting the source first to at least one control bottle having a known volume of liquid reagent so that the pressurized gas is supplied to the control bottle to calibrate the pressure build-up as a function of the known volume, c) connecting the source second to a test bottle of unknown amount of liquid reagent so that the pressurized gas is supplied to the test bottle, d) comparing the pressure build-up of the test bottle with that of the at least one control bottle, the connecting steps of steps b) and c) comprising supplying the pressurized gas at a variable flow rate at the fixed pressure so as to measure the variation in flow rate caused by variations in liquid volume present in the test bottle, the variable flow rate and the infinite source of fixed gas pressure being sufficient, over an extended period of time, to produce a final predetermined end-point pressure that is the same in both the control bottle and the test bottle; and e) generating a signal indicative of the predicted remaining liquid volume in the test bottle from the comparison in step d). A method as defined in claim 1 wherein the step d) comprises comparing the difference in the rate of pressure build-up in the test bottle compared to the control bottle at a fixed time that is the same time. for both the control bottle and the test bottle. A method as defined in claim 1, wherein the step d) comprises comparing the difference in time it takes for a fixed pressure to be reached in the test bottle compared to the control bottle, the fixed pressure being the same fixed pressure for both the control bottle and the test bottle. A method as defined in claim 1 or claim 2, wherein the step b) connects the source to two control bottles, each containing a different amount of liquid reagent, and the step d) includes the creation of a continuum of pressure build-up conditions based upon the pressure build-up in both of the control bottles. A method as defined in claim 4, wherein one of the control bottles is substantially empty and the other control bottle is substantially full. A method as defined in any one of claims 1 to 5, wherein the comparison of pressure build-up in step d) is done at a time selected to be prior to a final pressure condition in the bottle, both for the control bottle and for the test bottle, the time being the same in both. A method as defined in any one of claims 1 to 6, and further including the step of generating an error signal indicative of the absence of a bottle at the test station, in the event the step d) detects no increase in pressure above ambient. A method as defined in any one of claims 1 to 7, and further including the step of signaling for the replacement of the bottle at any station which produces a comparison of liquid volumes indicative of liquid volumes approaching zero.

Inventors: HIGGINS MICHAEL ANDREW, HYDE DAVID D, RIALL JAMES DANIEL, HIGGINS, MICHAEL ANDREW, HYDE, DAVID D., RIALL, JAMES DANIEL
Applicants: JOHNSON & JOHNSON CLIN DIAG, JOHNSON & JOHNSON CLINICAL DIAGNOSTICS, INC.
Application year: 1995
Main classification: G01F19
IPC codes: G01F23, G01F17, G01F22