JPH023467B2 - - Google Patents

Description

Claim 1: A test element that receives a predetermined amount of sample fluid from a metering device and produces a response proportional to a selected analyte in the fluid, and one type is used for one specific analyte. A device for sensing a sample fluid containing a significant proportion of water placed on one of two or more types of a device 62 for irradiating onto the element;
62a; 62b, 80; 80; 62c, 82, 8
6, a sensor device 66, 66a; 66b for detecting the intensity of the radiant energy in the band absorbed by the water received from the element and producing an output proportional to the intensity;
66c; the sensor device 66, 66a; 66b; 66c;
is adapted to produce a first output from the radiant energy received before fluid is dispensed onto said element 15 and a second output after fluid is dispensed onto said element 15. and a processing device 67; 67
c is provided to compare the difference between said first and second outputs to a predetermined value corresponding to a sufficient amount of fluid on the element and to provide a signal if the amount of fluid is not sufficient to produce a correct response. A sample fluid detection device characterized in that the sample fluid detection device is configured to generate

2. The device according to claim 1, wherein the device for emitting radiant energy comprises a device 80 arranged on one side of the element for irradiating the element with a radiation beam, and the sensor device 66b is arranged on one side of the element. A detection device for a sample fluid, characterized in that the device is arranged on the opposite side of the element and is adapted to detect the intensity of radiant energy passing through the element.

3. The device according to claim 1, wherein the device for applying radiant energy comprises a device 62; 62a; 6 for applying a beam of radiation to one side of the element.
2b; 62c, 82, 86, wherein the sensor device 66; 66a; 66b; 66c detects the intensity of radiant energy reflected from the surface.

4. Device according to claim 1, characterized in that the radiation beam irradiating device 62 is an incandescent lamp with a lens end 63.

5. The device according to claim 1, wherein the element 15 is supported for movement relative to the sensor device 66a and the processing device 6
7 is a detection device for a sample fluid, characterized in that it is configured to integrate the output received from the sensor device 66a while the element moves relative to the sensor device and estimate the volume of the droplet based thereon.

6. The apparatus of claim 1, wherein the sensor device is adapted to produce a single output, which output is produced after fluid has been metered onto the element, and wherein the sensor device A device for detecting a sample fluid, wherein the device is configured to compare the single output to a predetermined value corresponding to a sufficient amount of fluid on the test element.

7. In the device according to claim 1, 3, or 4, the sensor device 66; 66a;
66c is a sample fluid sensing device comprising a lead sulfide cell with an integral filter that passes a narrow band of radiant energy including a wavelength of 1.945 microns.

8. A sample fluid detection device according to claim 1 or 3, characterized in that the radiation beam irradiating device 62a and the sensor device 66a are provided above the element 15. .

9. The device according to any one of claims 1, 3, 4 and 7, wherein the device for irradiating the radiation beam 62; 62b; 62c, 82,
86 and the sensor device 66; 66b; 66c is arranged below the element 15.

10. In the device according to claim 1 or 3, the beam irradiating devices 62c, 8
2, 86 is a device 8 that irradiates the surface with an annular image;
4, wherein the inner diameter of the image is sized according to the desired amount of sample fluid.

11. The device according to claim 3, wherein a device 80 is provided for irradiating a radiation beam on a surface opposite to the one surface of the element 15, and the sensor device 66b is provided with a radiation beam from the irradiation device 80. A sample fluid sensing device configured to sense the intensity of radiant energy transmitted through a slide.

12. The device according to claim 10,
A sample fluid detection device, wherein the difference between the outputs is proportional to the volume of the droplet.

13 The volume of a sample fluid containing a significant percentage of water is measured on an analytical slide, one type of which is used for one specific analyte and which has a constant reflectance. one of a plurality of types having a range, the reflectance is proportional to the volume of fluid on the slide 15, and
A sample fluid detection device comprising a device 62c for irradiating a radiation beam onto the surface of the slide 15, and a sensor device that detects the intensity of the radiant energy reflected from the surface and generates an output according to the intensity, The sensor device 66c has a first output due to radiant energy received from the surface before fluid is metered onto the slide, and a second output due to radiant energy received after fluid is metered onto the slide. 2 outputs, and a processing device 67c compares the difference between the first and second outputs with a range of reflectance corresponding to the one type of slide 15 and performs a measurement on the slide 15. A sample fluid detection device, characterized in that it assumes the volume of a placed fluid.

14. The device according to claim 13,
An apparatus for detecting a sample fluid, wherein the radiation beam irradiating device 62c is a lamp that produces radiant energy within a spectral band including 1.945 microns.

15. The device according to claim 13,
A device 84 comprising an annular aperture 85 is provided, which irradiates the radiation beam 62c and the slide 15.
a sample fluid sensing device interposed between the sample fluid and the sample fluid detector, the device being adapted to illuminate an annular region 88 on the surface.

16. The device according to claim 13,
A sample fluid detection device characterized in that a light beam cutter 87 is provided between the radiation beam irradiating device 62c and the slide 15.

17. The device according to claim 13,
The processing device 67c has a computer 96,
The sample fluid detection device is further characterized in that the reflectance range is stored therein.

18 A method for sensing a sample fluid containing a significant percentage of water on an analytical slide that receives a predetermined volume of sample fluid and produces a response proportional to a selected analyte within the fluid, said slide comprising one Comparison when the slide is loaded with fluid due to the relatively high reflectance when the model is chosen from two or more models for one specific analyte and when the slide does not support the fluid. irradiating the dry slide with a beam of radiation before the metering of fluid onto it, with a constant reflectance range varying from a low reflectance to a low reflectance; detecting the intensity of radiant energy in a band that is absorbed; applying radiant energy to the slide after metering it onto the slide; detecting the intensity of radiant energy in a band that is absorbed by the water reflected from the slide; and comparing the radiant energy reflected from the dry slide with the radiant energy reflected from the slide after metering of fluid. and comparing the difference to a predetermined value within a range of reflectance of the slide to determine whether sufficient fluid has been metered onto the slide to produce a correct response. A method for detecting a sample fluid.

19 In the method according to claim 18,
A method for detecting a sample fluid, characterized in that the intensity of the radiant energy is detected in an infrared region.

20 In the method according to claim 18,
A method for detecting a sample fluid, wherein the radiant energy is applied to form an annular image on the slide, the inner diameter of the image being sized according to the desired amount of sample fluid.

DETAILED DESCRIPTION The present invention relates to the detection of sample fluid on a type of analytical slide that receives a predetermined amount of sample fluid and produces a response proportional to a selected analyte within the fluid. More particularly, the present invention relates to a method and apparatus for determining whether a sufficient amount of fluid has been dispensed onto an analysis slide to produce an appropriate response.

Recently, nearly flat analytical slides have been developed for use in the detection of selected analytes in biological fluids. Slides are increasingly being used in automated and highly efficient analytical equipment. In processing such slides, a predetermined amount of biological fluid, for example 10 microliters, is metered onto the slide and a reflectance reading of the slide is taken after a suitable hold time. The volume of fluid metered onto the slide must be controlled within certain limits to obtain acceptable test results. It is therefore important to know whether the metering device is functioning within these limits.

Metering devices used in medical equipment are designed to push fluid out of a metering tip using a pressurizing system. One way to know if a metering device is working properly is to note the pressure change in the pressurized system as fluid is being metered. However, such methods are not sensitive enough for accurate testing performed on most analytical instruments. Furthermore, this method cannot detect whether the fluid has been placed in the correct position on the analysis slide. A pressure sensitive metering method of the type described above is disclosed in US Pat. No. 4,041,995.

Devices for measuring the moisture content of sheet materials such as paper are well known. For example, U.S. Pat.
No. 3,471,698 discloses an infrared absorption analyzer that detects the presence of a thin film of dirt with a certain infrared absorption band on a reflective surface. Radiant energy containing a selected portion of infrared radiation is directed at and reflected from the surface being tested. The reflected radiant energy is sensed to determine the amount of reflection in the band of wavelengths in which the dirt to be detected has strong infrared absorption, and the amount of reflected infrared radiation is also measured in adjacent wavelength bands where the dirt does not have strong infrared absorption. Wavelength bands are also sensed. A comparison of the amount of reflected radiant energy in the two bands provides an indication of the amount of contamination on the surface.

Moisture analyzers such as those described above require complex optical and sensing equipment and are not suitable for use in medical equipment.
Furthermore, several structurally different types of slides are required for different analytes, and each of these types has a different reflectance. Therefore, in some cases, the wet reflectance of one type of slide may be very close to the reflectance of another type of dry slide. Devices that detect fluid on analysis slides must be able to properly process signals from all types of slides.

It is an object of the present invention to solve the above-mentioned problems of the prior art and to provide a new method and apparatus for determining whether an analytical slide has sufficient sample fluid to produce a correct test result. The present invention is particularly useful for use with different types of biological fluid analysis slides where the slides receiving the sample fluid have significant differences in structural properties.

According to one aspect of the invention, an apparatus is provided for sensing a slide fluid containing a significant percentage of water on a test element. the element is adapted to receive a predetermined amount of sample fluid from the metering device and produce a response proportional to a selected analyte within the fluid;
The element is selected from two or more types, each type adapted for use with a particular analyte. This device consists of a device that irradiates an element with radiant energy that includes wavelengths that are absorbed by water, and a device that senses the intensity of radiant energy within the band that is absorbed by water that is received from the element, and outputs an output that is proportional to the intensity. and a sensor device that produces
The sensor device is adapted to produce a first output due to the radiant energy received before the fluid is metered onto the element and a second output after the fluid is metered onto the element. A processing device compares the difference between the first and second outputs to a predetermined value corresponding to a sufficient amount of fluid on the element and generates a signal when there is insufficient fluid to provide a proper response. It is characterized by its shape.

According to another feature of the invention, an apparatus is provided for sensing a sample fluid containing a significant percentage of water for use in determining the volume of a sample fluid on an analytical slide. This slide is one of several types, each adapted for use with a particular analyte and having a range of reflectances, which reflect the volume of fluid on slide 15. This device consists of a device that directs a beam of radiant energy onto the surface of the slide, and a sensor device that detects the intensity of the radiant energy reflected from this surface and produces an output proportional to that intensity. a first output of radiant energy from the surface of the slide before the fluid is metered onto the slide; and a first output of radiant energy received from the surface after the fluid is metered onto the slide. and a processing device compares the difference between the first and second outputs to a range of reflectance values corresponding to one type of slide as previously described and weighed on the slide. It is characterized by the fact that it assumes the volume of the fluid.

According to the present invention, a method is provided for detecting a sample fluid containing a significant percentage of water on an analytical slide. wherein the slide is of a type that receives a predetermined amount of sample fluid and produces a response proportional to a selected analyte within the fluid, each having a relatively high reflectance when the slide is devoid of fluid. This method involves selecting from two or more slides, each used for a particular analyte, having a range of constant reflectance from 100 to a relatively low reflectance when the fluid is placed on the slide. irradiates a dry slide with radiant energy before dispensing a fluid onto it, detects the intensity of the reflected radiant energy in the band absorbed by water from the dry slide, and detects the intensity of the reflected radiant energy in the band absorbed by water from the dry slide. After the fluid has been weighed and placed, radiant energy is irradiated onto the slide, and the intensity of the radiant energy in the band that is absorbed by water is reflected from the slide after the fluid has been weighed and placed is detected and reflected from the dry slide. The difference in intensity between the radiant energy and that after weighing is compared with a predetermined value within the reflectance range of the slide,
Determine whether enough fluid has been metered onto the slide to produce a correct response.

In one embodiment of the invention, a radiant energy source is provided to direct a beam of radiation onto the surface of an analysis slide supported in the weighing position, and a sensor detects the intensity of the radiant energy reflected from the surface of the slide. It is designed to detect and generate an output proportional to its strength. The sensor produces a first output based on radiant energy directed onto the dry slide and a second output based on radiant energy reflected from the slide after fluid has been metered. The difference between the first and second outputs is compared to a predetermined value within a range for the particular type of slide being used, and a signal device is used to signal when the amount of fluid is not sufficient to produce a proper response. is now operational.

The invention disclosed herein is particularly advantageous for use with slides where the reflectivity of the slide varies depending on its type. The present invention can be used not only to determine whether the correct amount of fluid is placed on the slide, but also to estimate the volume of fluid on the slide. Detection can be performed using a single wavelength band, so no complex optics or sensing equipment is required.

Embodiments of the invention will be described by way of example with reference to the drawings.

FIG. 1 is a perspective view of a type of chemical analysis apparatus adapted to use the invention disclosed herein; FIG. FIG. 3 is a perspective view of the analysis slide and optical elements in another example of a drop detection device; FIG. 4 is a perspective view of a further example of a drop detection device; FIG. 5 is a perspective view of an optical system of another embodiment of the invention; FIG. 6a is a droplet detection device shown in FIG. 2; FIG. 6b is a diagram of the signal produced by the sensor device of FIG. 6a; FIG. 7a is a diagram of the signal processing device for the droplet detection device of FIG. 7b and 7c are diagrams illustrating the signals produced by the sensor arrangement of FIG. 7a.

The invention will now be described in connection with an analytical device for performing quantitative chemical analysis of biological fluids such as serum. However, the present invention is not limited thereto and may be used with other types of devices in which it is necessary to sense fluids metered onto different types of substrates.

One form of test element or analysis slide for use in the present invention is disclosed in commonly assigned U.S. Pat.
It is disclosed in the specification of No. 3992158. The test element disclosed herein is formed as a multilayered element containing the necessary reagents that react with components of a biological fluid, such as serum, placed thereon. Certain reactions colorimetrically change the optical density of the element.
This element is sensed by a reflectometer;
The amount of light reflected from the element changes in response to the reaction and is an indication of the amount of a particular analyte within the fluid.

As used below, "above", "below", "below", "vertical", "horizontal", "top" and "bottom" refer to the orientation of the described device in its normal operating position. use

As one embodiment of the invention, an analytical device 12 is shown in FIG. 1, which is of a type adapted to use a test element in the form of a generally flat analytical slide. The analyzer 12 has a slide supply device 14 for a colorimetric analysis slide 15 (FIG. 2) and a slide supply device 16 for a potentiometric analysis slide (not shown). Weighing device 1
8 is a cup 1 supported by a sample tray 20
The sample dispensing device 30 is configured to aspirate sample fluid from the sample dispensing device 30 and place a predetermined amount of the fluid onto an analysis slide supported within the sample dispensing device 30 . A second metering mount (not shown) operates in communication with metering device 18 and is also adapted to place reference fluid on the potentiometric analysis slide. After the metering action, the slide dispensing device 30 places the potential difference analysis slide in the incubator 22 and also places the analysis slide 15 in the incubator 24.
put it inside. Incubators 22 and 24 are analyzers 23 and 25
Measure the charge within the slide as a result of the fluid on the analysis slide.

As shown in FIG. 2, metering device 18 includes a dispenser 40 having a dispensing head 46 adapted to receive a disposable metering tip 48 and via tube 50 for pumping. (not shown). During a metering operation, a positioning device (not shown) for the distributor 40 is positioned on the tray 20.
It is adapted to move the dispensing head 46 to the upper position, where it is lowered to pick up the disposable metering tip 48, and the head is then moved to the sample cup 19 where it is aspirated into the supply of sample fluid. I do. After aspiration of the sample fluid, the dispensing head 46 connects the dispensing device 3
guide 116 which positions the tip 48 relative to the slide 15 in the metering position. Tip 4
Once 8 is positioned, the metering pump is activated for a predetermined period of time to meter the desired amount of sample fluid onto the analysis slide 15. The tip 48 remains in the metering position for about 1/10 seconds after the metering pump stops, completing the metering action, and then the distributor 40 moves to the second metering position.
Return to the original position shown in the figure. In most cases, more than one analysis will be performed on a particular sample fluid. Distributor 40 while additional analysis is performed.
will go up and down for each new slide. After the desired amount of sample fluid has been used, the used tip 48 is discharged into the container 110.

The droplet detection apparatus 60 of the present invention, shown in FIG. Irradiate the bottom surface of 15. A sensor 66 is adapted to receive reflected radiant energy, indicated by arrow 68, from slide 15. Sensor 66 is a lead sulfide (PbS) type electro-optical cell with an integral filter (not shown) that passes infrared radiation at a wavelength of 1.945 microns. Radiant energy at a wavelength of 1.945 microns is within the absorption band of water or moisture contained in slide 15. Therefore, a wet slide is characterized by a relatively weak output of the sensor 66 because the radiant energy is absorbed by the water-bearing sample. sensor 66 and lamp 62
is oriented with respect to slide 15 so that specular reflections from it that undergo diffuse reflection and return to sensor 66 are minimized.

The droplet detection device 60 can detect moisture in the same way, whether it is incident from the top of the slide 15 or from the bottom. Limitations imposed by the analyzer will determine which location is desirable. The analyzer 12 is constructed such that the slide is detected as free of moisture by the sensing device most conveniently positioned below the slide 15 in the metering position prior to metering the sample fluid. A second reading after the metering operation can be taken by the same sensor. One advantage is that readings taken before and after fluid is metered onto slide 15 can be compared. Slides 15 for different tests have different constructional characteristics that change the reflective properties of the slide. It is not always possible to distinguish between the sensor output produced from one type of wet slide and the output from another type of dry slide. Comparing the first reading (dry) and the second reading (wet) for each slide eliminates the effects of different reflective properties of different types of slides.

A device 67 for processing the output from sensor 66 is shown in FIG. 6a. If the resistance of sensor 66 is low, the output sent to amplifier 70 will be A in FIG. 6b.
As shown in (dry reading), it is relatively low. The output of amplifier 70 for dry readings is sent to a "sample and hold" circuit 71 where the output is stored by trigger pulses from computer 75. After the fluid is metered onto the slide 15, no less radiant energy is reflected from the slide 15. The resistance of sensor 66 increases and amplifier 70
The output sent to B (wet reading) is shown in Figure 6b.
increases as shown by . At appropriate times in the measurement cycle, computer 75 allows the dry reading stored in sample and hold circuit 71 to appear at input Aa of differential amplifier 72, and at the same time 7
A trigger pulse to 3 sends the current output of amplifier 70 (wet reading) to input Ba of amplifier 72.

Amplifier 72 receives inputs Aa and Ba and produces an output proportional to the difference between the dry and wet readings, and this output is sent to analog-to-digital converter 74, which converts the digital signal to computer 75. arise. Computer 75 compares the difference between the dry and wet readings to the stored value to determine whether a sufficient amount of fluid has been metered onto the slide. If a sufficient amount of fluid is not metered onto the slide 15, the computer 75 alerts the operator of the defective slide by sending a signal to the display device 76.

Computer 75 may be, for example, a programmable microcomputer of a conventional type. Methods of programming such computers are well known in the art and no further explanation is deemed necessary. Those skilled in the art will appreciate that the output from amplifier 72 may be sent to a comparator (not shown) that can be sent directly to display device 76 to produce an output when a predetermined condition is not met. can be easily understood.

Another embodiment of the invention is shown in FIG.
Here, the droplet detection device 60a includes a lamp 62a positioned above the slide 15 and a sensor 66.
It has a. In this example, the slide can be detected in motion. The diameter of the shaded area, which is proportional to the volume of the sample fluid, determines the duration of the wetness signal produced by sensor 66a. The quantitative assumption of the droplet volume is made by computer 7.
5. Signals are included in the computer software to distinguish between different types of slides. The type of slide must be made known to the computer, for example by means of a machine-interchangeable code affixed to the slide or to the support that supplies it to the analyzer 12, and the signal of the sensor 66a. Allows you to judge the content.

Another embodiment of the invention is shown in FIG. 4, in which a droplet sensing device 60b includes a lamp 62b and a sensor 66b arranged as in FIG. An auxiliary radiant energy source in the form of a lamp 80 is provided for slide 15 for reasons explained below.
The beam is designed to irradiate the top surface of the A filter that passes infrared rays is connected to the sensors 66 and 6.
It may be combined with sensor 66b as in 6a, or the filter may be a separate element as shown at 79 in FIG. One type of analysis slide 15 is designed to have a translucent layer rather than the usual opaque white layer. The result of this is to reduce the signal from the dry slide back to the sensor. The radiant energy partially passes through the slide without being reflected. Therefore, the signal of the difference between the dry reading and the wet reading is small. This small difference signal is nearly as large as the difference in signal between a dry slide and a wet slide when receiving only a small droplet (eg, 3 microns) on a highly reflective type of slide. If the analyzer is set to accept such a small difference signal as an indication of a good droplet on a translucent slide, very small droplets on other slides will also be tolerated. I end up. It is desirable to distinguish droplets larger than 6 microliters from smaller ones. This limit is arbitrary and can be set higher or lower depending on the sensitivity of the sensing device.

A lamp 80 is provided to focus light on the top surface of the slide 15, which is of a translucent type. The radiant energy from lamp 80, in addition to that from lamp 62b reflected by the slide, passes through the translucent slide to provide a drying reading comparable to a highly reflective type of drying slide. When sample fluid is applied to the slide, more radiant energy is absorbed by both lamps 62b, 80, and sensor 66b responds with a wet reading equivalent to the wet reading from the highly reflective nature of the slide. . The specific example shown in FIG.
It is possible to operate in light passing mode only, ie without lamp 62b. In such a case, sensor 66b is responsive only to radiant energy passing through the slide.

Another embodiment of the invention is shown in principle in FIG. Droplet volume sensing device 60c includes a lamp 62c that directs radiant energy in the direction of arrow 64c through a condensing lens 82 that images the lamp filament in the plane of an imaging lens 86. The radiation beam is bounded by a plate 84 having an annular aperture 85. Imaging lens 86 focuses the beam onto slide 15, producing an annular region 88 shown on slide 15 in FIG. An optical cutter 87, which is rotationally driven by a motor (not shown), cuts the beam in close proximity to the imaging lens 86. The reflected radiant energy, indicated by arrow 68c, is sensed by sensor 66c, which produces an output proportional to the intensity of the reflected radiation. The optical interrupter 87 allows a pulsed output to be generated by the sensor 66c.

The operation of the sensing device 60c is based on the principle that the area of the slide 15 wetted by sample fluid is proportional to the volume of sample fluid on the slide. Sensor 66c is a lead sulfide cell with an integral narrow band width filter (not shown).
selectively responds to energy at a wavelength of 1.945 microns. The water in the added sample strongly absorbs radiant energy at a wavelength of 1.945 microns. The sensing device 60c is placed in the weighing part of the analyzer such that readings are taken before and after sample weighing. The amount of energy reflected to sensor 66c is proportional to the dry area of the slide seen by sensor 66c. The output after the sample is distributed is compared to the output before distribution. The difference in output is proportional to the volume of sample on the slide. an aperture delimits a light beam that illuminates the underside of the analysis slide;
A circular area centered on the slide should be illuminated. The central dark area 89 is sized such that any unacceptable droplet volume will be completely within this area. If no difference in signal is seen between dry and wet, the slide is rejected as a dry slide. Signal processing must include identification of the slide type in order to correctly determine the signal and to correctly predict sample volume.

FIG. 7a shows a device for processing the signals produced by the droplet sensing device 60c (FIG. 5). The output from sensor 66c has an AC component in the form of a wave, as shown at 91, and the frequency is determined by optical shear cutter 87. The voltage across sensor 66c is sensed by amplifier 90 and the DC component is removed by capacitor 92 in series with the input to amplifier 90.

The output of amplifier 90 varies between a relatively strong signal for a dry slide and a relatively weak signal for a wet slide, as shown in Figure 7b. The output from amplifier 90 is sent to RMS/DC converter 93, which converts the pulsed signal into a continuous signal as shown in Figure 7c. The output for dry readings from transducer 93 is sent to sample and hold circuit 97. The pulses from the computer 96 to the sample and hold circuit 94 and the divider circuit 5 are such that they send both the dry A' and wet B' signals to the divider circuit 95, which circuit combines the dry signal and the wet signal. It produces an output representing a ratio equal to the difference divided by the dry signal. This ratio is sent to analog-to-digital converter 97, which sends the signal in digital form to computer 96. The ratio for each slide is compared by computer 96 to the stored value for the particular type of slide, and the volume of sample fluid is assumed based on the determined ratio.

In the above-described embodiment of the invention, wet and dry readings are taken for each slide. This ensures that the sensing device operates correctly over the full range of reflection characteristics in each of the different types of slides. Under optimal conditions and with appropriate programming of the computer, the initial dry reading of the slide is used to determine whether sufficient fluid has been dispensed onto the slide, at least for a large number of similar slide types. It can be done without taking. The reflectance for each type of slide is stored in the computer for the full range from dry to wet, and the reading when the slide is wet is compared to the stored value.