|
(11) | EP 0 480 208 A2 |
| (12) | EUROPEAN PATENT APPLICATION |
|
|
|
|
|||||||||||||||||||||||||||
| (54) | Test system timer |
| (57) A test system timer has been designed for measuring multiple time phases or sequences
of each of multiple test samples or points simultaneously. The timer contains multiple
internal clocks and a countdown time display area. Upon activation of the timer, an
entire sequence of multiple phases for the test sample is initiated. The timer has
visuals to permit the user to know how many test samples have been collected, which
phase of a timing cycle the test sample is in, the amount of time remaining in any
given phase, and alarms to alert the operator to action as needed. In addition, the
timer base has a retainer plate to securely hold a test sample carrier or associated
equipment. |
BACKGROUND OF THE INVENTION
1. Field of the Invention
[0001] This invention relates to a timer having multiple internal clocks to measure multiple time phases or sequences of each of multiple test samples or points simultaneously and a method by which this may be done.
2. Description of the Prior Art
[0002] Measuring the time course of any reaction simply requires the starting of a timing device at the beginning of the reaction and the stopping of the timing device at the end of the reaction. This timing procedure remains simple unless multiple samples are to be timed. If an ordinary timing device is used, the stopping of the timing device at the end of the reaction is not practical since additional samples are to be timed with the same device. Thus, an operator must time a reaction from start to finish and then time a second reaction from start to finish, etc. The longer the reaction or the larger the number of reactions to be measured, the more inefficient it becomes to use a single timing device to measure from start to finish of the reaction. One way to overcome this type inefficiency is to stagger the starting of reaction times and hence the stopping of the reactions. Such a process requires only one timing device, but the device must be kept running after the first reaction is completed. As any investigator who has used this process knows, the staggering of starting times usually results in an approximation of stopping times since the operator frequently has underestimated the time necessary between samples.
[0003] A second way to overcome this time inefficiency associated with multiple sample testing is to employ multiple timing devices. Such a process insures the accuracy of stopping times but requires a number of timing devices equal to the number of samples being tested.
[0004] The above limitations become more acute when the measuring of each test sample involves multiple time phases. For example, in analytical chemical reactions there is a specified time for a reaction to proceed after which the extent of the reaction is provided by some evidentiary measurement. For example, a reactant "T" of unknown concentration will react with a known concentration of a reactant "C" to provide a product "R" whose concentration may be conveniently measured, "R" being taken as a measure of the original concentration of reactant "T".
T+C=R
[0005] When the extent of the reaction is time dependent, as in enzymatic reactions, the measurement of "R" at a given time and under controlled conditions is essential to determine the concentration of "T". This finite period of time may be designated as the incubation period. If the incubation period is longer than the collection time, the analyst may utilize the incubation period to collect multiple samples. Multiple clocks may be used to time these multiple reactions, as shown.
! = Beginning of test and sample collection
C = End of specified collection period
X= = Time at which R is measured
To = Time at which multiple collections begin
T1 = Time all measurements of R are complete
[0006] In the example shown, up to three test samples may be collected to utilize the fallow time occasioned by the incubation period. The number of test samples that may be collected during the incubation period required for the first test sample is dependent on the relationship between time required for collection and the incubation period. More samples may be collected if the ratio of the incubation to collection time is increased.
[0007] In the example above, the reaction could be stopped short by removing T or C from the system, or by otherwise making their reaction impossible in some way. In such a case, R could be measured at a convenient later time. This method is frequently employed in a laboratory.
[0008] If the reaction may not be stopped short and if the rate of reaction is such that there is not a single time but a time period during which the analytical measurement of the extent of the reaction may be evaluated, an evaluation "window" may be created. This allows multiple samples to be collected, incubated and evaluated without the need to stop short the reaction. This invention discloses a device and a method by which this may be done.
[0009] An example of a general description is provided below.
! = Beginning of test and sample collection
C = End of specified collection period
X= = Time at which R may first be measured
K= = Time at which R may last be measured
To = Time at which multiple collections begin
T, = Time at which no other samples may be collected
Tv = Time before which R may not be measured
Ts = Time after which R may not be measured
[0010] It is clear in this generalized example that more than three samples might be collected. The timeline also shows that there are three distinct time periods as a result as described by the time between To and Tr (known as the TEST phase), the time between Tr and Tv (known as the VIEW or incubation phase), and the time between Tv and Ts (known as the EVALuation phase).
[0011] A further generalized example below shows that collection of a subsequent test sample may be begun at a time later than the end of the collection of the first sample, and that three time phases, namely TEST, VIEW and EVAL remain but may be different in relative duration.
[0012] The detailed description of the invention further details how a timing device may be used to assist the analyst to collect, incubate and evaluate multiple test samples in a time dependent reaction.
SUMMARY OF THE INVENTION
[0013] A test system timer provides an adjunct to single or multiple test sampling. Use of the timer facilitates the simultaneous evaluation of multiple test samples. The timer contains multiple internal clocks and a countdown time display area. Upon activation of the timer, an entire sequence of multiple phases for the test sample is initiated. The timer includes visuals to permit the operator to know how many test samples have been collected, which phase of a timing cycle the test sample is in, the amount of time remaining in any given phase, and audibles or alarms to alert the operator to action as needed. In addition, the timer base or housing has a hold down area or retainer plate, with right-handed and left-handed access, to securely hold a test sample carrier or associated equip-ment during timer operation, e.g. during sample collection.
[0014] In a preferred embodiment, the timer is designed for measuring three specific phases of each of multiple test samples for the enzyme elastase. The three specific phases of each test sample are a TEST phase for test sample collection, a VIEW phase for test sample incubation, and an EVALuation phase for test sample analysis. In the preferred embodiment, the timer is comprised of a plurality of internal timing devices, a control panel, a plurality of alarms, and a retainer plate comprising right-handed and left-handed access to facilitate connection with an associated incubator box. The control panel includes two control buttons (a start button and an advance button) and a display panel having a running clock, a test indicator, and a timing sequence phase indicator.
BRIEF DESCRIPTION OF THE DRAWINGS
[0015] Further details are explained below with the help of the examples illustrated in the attached drawings in which:
Fig. 1 is a top view of an incubator box or carrier.
Fig. 2 is a side elevation of the incubator box or carrier.
Fig. 3 is an enlarged plan view of a timer showing the carrier in place in phantom lines.
Fig. 4 is a side elevational view of the timer showing the carrier in place in phantom lines.
Fig. 5 is a front elevational view of the timer showing two different positions that the carrier can be placed on the timer.
DESCRIPTION OF THE PREFERRED EMBODIMENT
[0016] Fig. 1 is a top view of a test strip carrier or incubator box (10). The test strip carrier (10) is the subject of a separate patent application, attorney docket No. 1579-2CIP, the contents of which are hereby incorporated by reference. As seen in Fig. 2, the carrier (10) has a top or lid (11) that folds back from the carrier (in the direction of the arrow). The carrier is designed for use with and connection to the timer of this application.
[0017] Fig. 3 is a plan view of the timer. The display panel (12) shows a running clock (14), a test number indicator (16) and a timing sequence phase indicator (18). The timing sequence phase indicator (18) displays visuals for only one of the three phases, namely, TEST, VIEW or EVAL, at a given time. In addition to the display panel (12), the control panel or anterior portion of the timer also contains a start button (20) and an advance button (30).
[0018] Posterior to the display panel (12) is a retention mechanism or test strip carrier retainer plate (40) designed to facilitate connection with associated equipment e.g. to hold the test strip carrier (10). The retainer plate (40) of the timer contains a center screw (42) which may be removed for cleaning under the plate. The retainer plate (40) forms a pair of side slots (44) with the main body or top housing (50) perpendicular to the lateral sides (46) of the timer. The side slots (44) may be seen in Fig. 3 and Fig. 4. The side slots (44) are for connecting and holding the test strip carrier (10). The retainer plate (40) has a pair of protrusions (not shown in the figures) along each side of the side slots (44) for interlocking with the test strip carrier (10). Fig. 5 shows that the carrier (10) may be attached from either lateral side of the timer e.g. either right-handed or left-handed access. Thus, the timer may be used by either a right-handed or left-handed operator.
[0019] In addition, Fig. 4 shows that the lateral sides (46) of the timer adjacent the test strip carrier retainer plate (40) are higher than the lateral sides of the timer adjacent the display panel (12). As a result of this design, the test strip carrier (10) is elevated from the surface holding the timer. The elevation allows the top or lid (11) of the carrier (10) to fold back from the carrier without hitting the surface below the timer. This result can be clearly seen in Fig. 5.
[0020] The timer is designed to measure multiple time phases or sequences of each of multiple test samples or points simultaneously. For example, each test sample can be divided into a test phase (TEST), a view phase (VIEW) and an evaluation phase (EVAL). Multiple test points can then be measured simultaneously. Multiple timing is accomplished through the use of a plurality of internal timing devices.
[0021] In the TEST phase for a single sample, the timer measures the time available for collection. The test collection is begun, and the timer start button (20) is immediately pressed, causing the test number indicator (16) to flash the character # and display the number 1 on the display panel (12) along with the running clock (14) displaying the total time available for the TEST phase. The test number indicator (16) will flash during the specified period of collection, after which a single beep is sounded, the character # disappears from view and the number 1 ceases to flash but is continuously displayed.
[0022] Collection of multiple samples proceeds by depressing the start button (20) as each sample collection period is begun. For example, the start button (20) is again depressed when collection of a second test sample is begun; the character # and the number of the sample being collected flash. After the specified collection period, a beep is sounded to give warning that the collection of sample for this test is completed, the character # disappears from view, and the number 2 ceases to flash but is continuously displayed. This procedure is continued until the TEST period is concluded. At the end of the TEST period the timer sounds a double beep, the TEST display is removed and replaced by the word VIEW or its equivalent, and the running clock will display the time remaining in the VIEW phase. The timer algorithm permits the analyst to depress the advance button (30) twice in rapid succession in the case the collection of samples is completed before the automatic display of VIEW occurs as described above. This causes the word TEST to be removed and replaced with the word VIEW. All other aspects of the timer sequencing prior to the EVALuation period remain the same.
[0023] At the end of the VIEW phase, a beep and alarm sound and the word VIEW is replaced by EVAL and the running clock displays the time remaining in the evaluation phase. During the evaluation window, the measurement of "R" is made and recorded. At the end of the evaluation period a longer continuous alarm is sounded and the timer shuts itself off.
[0024] In the event that the operator desires to create a total interruption of the test, the timer has a feature to reset all circuits and shutdown. This is accomplished by two, quick successive depressions of both the start and advance buttons simultaneously.
EXAMPLE
[0025] This example describes how the timer is used in conjunction with a test for the presence of the enzyme elastase in a given solution.
[0026] Test strips were prepared from filter paper. Whatman 541 filter paper (0.16 mm in thickness) was sandwiched between two plastic portions so that more than one mm of the filter paper was exposed and available for absorption of biological material and one mm of the filter paper was between the two plastic portions. The filter paper was then impregnated with substrate and the test strips cut to size.
[0027] The filter paper was impregnated with substrate by wetting the filter paper exposed tips of test strips in 0.85 millimolar methoxysuccinyl-alanine-alanine-proline-valine-7-amino-4-trifluoromethyl coumarin (Lot # AP65 from Enzyme Systems Products, Livermore, California) in elastase substrate buffer (0.5 M NaCI, 0.1 M HEPES(N-2-hydroxyethyl-piperazine N-2-ethanesulfonic acid), pH 8.14). The impregnated filter paper was allowed to dry overnight. Following drying, test strips of eight mm in length and two mm in width were cut so that one mm of impregnated filter paper was exposed and available for absorption of biological fluid.
[0028] The impregnated test strips were used to test for elastase as follows. An elastase test solution was prepared by dissolving 1.2 mg of elastase (Biozyme, San Diego, CA) in elastase substrate buffer described above so that a final concentration of 2 mg/ml elastase enzyme was obtained. The stock solution and serial dilutions (50 to 5 ug/ml elastase) were tested.
[0029] The test strips were tested in an assay in such a way that final evaluations of a maximum of six test strips were made no less than four and no more than eight minutes after exposure to the test enzyme. Thus, a first test strip, impregnated with methoxysuccinyl-alanine-alanine-proline-valine-7-amino-4-trifluoromethyl coumarin was inserted into an elastase test solution for 15 seconds. When the first test strip was inserted into the solution, the start button of the timer was depressed, a short beep was sounded, the strip indicator flashed the character # and a flashing number 1 was displayed on the display panel. Simultaneously with the depressing of the start button, the running clock displayed 3 minutes and 45 seconds, the time remaining in the test mode for the collection of test samples. When the running clock reached 3:30, a single beep sounded, the character # disappeared from view and the number 1 ceased to flash but was continuously displayed. At this time, the first test strip, containing approximately 0.9 ul of elastase test solution, was removed from the test solution, attached to the adhesive layer in an incubator box and allowed to incubate at room temperature. The incubator box was securely attached to the timer via the timer's side slots and protrusions.
[0030] A second test strip was inserted into the elastase test solution for 15 seconds. When the second test strip was inserted into the solution, the start button was depressed, a short beep was sounded, the strip indicator flashed the character # and a flashing number 2 was displayed on the display panel. When the second test strip was inserted into the solution and the start button depressed, the running clock displayed 3 minutes and 15 seconds, the time remaining in the test mode for the collection of test samples. When the running clock reached 3:00, a single beep sounded, the character # disappeared from view and the number 2 ceased to flash but was continuously displayed. At this time, the second test strip was removed from the test solution, attached to the adhesive layer in an incubator box and allowed to incubate at room temperature.
[0031] The collection and timing procedure was repeated for test strips 3, 4, 5 and 6. When the sixth test strip was inserted into the solution and the start button depressed, the running clock displayed 1 minute and 15 seconds. When the clock reached 1:00, a double beep sounded, the character # disappeared from view and the number 6 ceased to flash but was continuously displayed. The maximum number of samples had been collected with 1 minute remaining in the test or collection phase and the timer automatically switched to the view phase. The running clock displayed 3:45 which was the time remaining for the incubation of the sixth test strip so that all six strips would have incubated for at least four minutes and be evaluated in less than eight minutes. At the end of the 3 minute and 45 second view phase, a beep and chime alarm sounded and the running clock displayed 1:30, the time remaining in the evaluation phase so that all six strips would be evaluated between six and one-half and eight minutes, i.e., within the predetermined four to eight minute window.
[0032] The six test strips attached to the adhesive strip in the incubator box were evaluated for fluorescence in a viewing chamber of a viewer equipped with a longwave ultraviolet lamp. The viewer is the subject of a separate patent application, attorney docket No. 991, the contents of which are hereby incorporated by reference. The incubator box containing the test strips was placed within the viewing chamber and the test strips were compared to a positive color standard mounted within the viewing chamber. Reactive elastase was determined by measuring a fluorescing leaving group which was released by the hydrolytic action of elastase upon the substrate and visually assayed in the viewing chamber. After one minute and 30 seconds, the alarm of the timer sounded a continuous (relatively long sounding) alarm indicating the end of the evaluation phase and shut itself off.
1. A timer for the measuring of multiple phases of each of multiple test samples simultaneously,
comprising:
a. a plurality of internal timing devices,
b. a control panel,
c. a plurality of alarms, and
d. a retention mechanism to facilitate connection with associated equipment.
2. The timer of claim 1 wherein said control panel comprises
a. a display panel having
(1). a running clock,
(2). a test indicator, and
(3). a timing sequence phase indicator,
b. a start button, and
c. an advance button.
3. The timer of claim 1 wherein said retention mechanism comprises a retainer plate
with right-handed and left-handed access.
4. A timer for the measuring of multiple phases of each of multiple test samples simultaneously,
comprising:
a. a plurality of internal timing devices,
b. a control panel comprising
(1). a display panel having
(a). a running clock,
(b). a test indicator, and
(c). a timing sequence phase indicator,
(2). a start button, and
(3). an advance button,
c. a plurality of alarms, and
d. a retainer plate comprising right-handed and left-handed access to facilitate connection with associated equipment.
5. A timer for the measuring of three specific phases of each of multiple test samples
simultaneously, comprising:
a. a plurality of internal timing devices,
b. a control panel comprising
(1). a display panel having
(a). a running clock,
(b). a test indicator, and
(c). a timing sequence phase indicator,
(2). a start button, and
(3). an advance button,
c. a plurality of alarms, and
d. a retainer plate comprising right-handed and left-handed access to facilitate connection
with associated equipment,
wherein the three specific phases of each test sample comprise
e. a test phase for test sample collection,
f. a view phase for test sample incubation, and
g. an evaluation phase for test sample analysis.
6. A method for the timing of multiple time sequences for each of multiple test samples
simultaneously, comprising the steps of:
a. determining a time window for an initial time sequence wherein the length of the time window is dependent on the time required for completion of each of the multiple time sequences,
b. initiating the measurement of a first time sequence for a first test sample,
c. repeating the initiation of the measurement of a first time sequence for each of the multiple test samples within the time window, and
d. performing additional measurements of time for each of the multiple time sequences for each of multiple test samples as in steps a., b. and c.
7. The method of claim 6 wherein there are three time sequences to be measured for
each test sample.
8. The method of claim 7 wherein the three time sequences are:
a. a test sequence for test sample collection,
b. a view sequence for test sample incubation, and
c. an evaluation sequence for test sample analysis.
9. A method of determining the disease state of multiple periodontal sites in a continuous
uninterrupted sequence comprising
a. collecting a sequence of individually timed visual and audibly signaled samples from periodontal pocket areas of a patient's mouth during a unitary overall single timed visual and audibly signaled period;
b. incubating said sequence of samples simultaneously during a timed visual and audibly signaled period;
c. evaluating said incubated sequence of samples sequentially during a single timed visual and audibly signaled period.
10. The method of claim 9 wherein said timing and visual and audible signaling is
all done with a unitary control means.
11. The method of claim 9 wherein said collecting of the sequence of individually
timed visually and audibly signaled samples are visually signaled cumulatively sequentially
by a blinking number in the sequence being displayed upon individual collection activation
by an operator and blinking for the timed period at which time it stops blinking but
remains displayed until completion of the entire unitary overall single timed visual
and audibly signaled period, said collection of the sequence of individually timed
visually and audibly signaled samples are audibly signaled by a single beep sound
at the end of each timed period from said individual collection activation by the
operator, said first collection sequencing activation activating the master allowable
collection time period the end of which is signaled by a double beep sound;
said incubation period timer is initiated by said first collection sequencing activation and the end of the period signaled audibly with a single beep and a chime alarm;
said evaluation period timing is initiated by said first collection sequencing activation and the end of the period is signaled by a continuous alarm;
said method including shuting of the timing mechanism at the end of said continuous alarm period.