Testing set,especially for biological fluides

The subject of the invention is a test kit, especially for biological fluids. The invention in particular, although not exclusively, relates to the testing of biological fluid samples that can be carried out by relatively unskilled persons, especially at home.

At present, home appliances for urine analysis are widespread, for example in pregnancy and ovulation tests. In the case of a pregnancy test, which only requires providing the user with a "yes / no" result, the currently available technology makes it easy to read the test result visually without the need for any auxiliary equipment.

Many such devices are based on the principles of immunochromatography, and they are usually provided with a hollow plastic housing containing a porous sampling strip containing pre-dispensed reagents. Reagents within the device may contain one or more direct labeled reagents, such as a dye gel, metallic sol (e.g., gold) or colored latex (e.g., polystyrene) in the form of microparticles that are visible to the eye when concentrated in a relatively small area of ​​the strip. The user only needs to apply a urine sample to one part of the housing to initiate the sample. The result of the test becomes visible to the naked eye within a few minutes without the need for further user interaction. Examples of such devices are described in EP-A-291194 and EP-A-3 83619. Collection of the sample is usually done by means of a paper element that is part of the device and which can easily absorb a sample of fluid, e.g. from a urine stream. Optionally, the paper element may protrude from the device housing to facilitate sample application. EP 292194 and EP 383619 disclose general-type sampling devices that can be advantageously read using the transmission-based system of the present invention. Neither of these two descriptions specifically indicates that optical transmission would be an ideal reading system.

The test strip reader known from EP 283285 uses optical transmission. However, although the optical system consists of a light emitting diode as a source and a photodiode as a sensor, the emphasis is on choosing the frequency and intensity of the light. There is no clear suggestion in EP 283285 that some special benefits are obtained when the light illuminating the test strip is diffused. There is no suggestion in EP 283285 that special measures have been taken to achieve dispersion. What's more, there is no mention that a separate diffuser should be placed in the optical path in front of the photosensitive diode. Japanese Patent JP 59214768 relates to a capillary tube blood testing system and uses light transmission through a tube. Although the light is to be uniform and of a certain wavelength, there is no mention of it being diffused. Another Japanese patent - JP 63134953 - refers to a system based on the reading of "test paper", which undergoes changes in color under the influence of reactions. An optical instrument is used to read the test result. However, since the test paper is placed in a cover that appears to have only one window, this optical reading system must

178 125 based on reflection rather than transmission. No mention is made of the benefits of using scattered light.

Test kit, especially for biological fluids, comprising at least one sampling device, provided with a porous, fluid-permeable carrier in the form of a strip and / or a sheet transmitting electromagnetic radiation, which contains at least one detection zone with the disclosed test result in the form of detectable material in the detection zone, wherein the sampling device carrier is housed in a housing forming part of the sampling device and provided with windows constituting the areas of electromagnetic energy transfer from an external source to the detection zone, and a reader of the test result from the sampling device to determine the degree of attenuation of electromagnetic radiation passing through the carrier due to the presence of detectable material bound in the detection zone, wherein the test result reader is provided with a receiving device for the sampling device, of the slot type, comprising at least the part of the sampling device which comprises a detection zone and a reading unit coupled to the receiving unit, and the reading unit is provided with at least one source of electromagnetic radiation and at least one electromagnetic radiation intensity sensor, wherein the detection zone of the sampling device lies in the path of electromagnetic radiation between the radiation source and at least one sensor, according to the invention, it is distinguished by the fact that in front of at least one sensor of electromagnetic radiation intensity, a diffuser is placed in the path of electromagnetic radiation between the radiation source and at least one sensor .

The radiation source is a source of scattered electromagnetic radiation, while the sampling device housing is provided with holes constituting the second areas of electromagnetic energy transmission. Both areas of electromagnetic energy transmission through the sampling device housing are in the path of electromagnetic radiation from the source of radiation through the sampling device, and the detection zones are located by electromagnetic radiation between the areas of electromagnetic energy transmission. The test result is disclosed in the detection zone in the form of detectable material bound in the detection zone, directly and / or indirectly to the binding reagent immobilized in the detection zone.

The receiving unit is preferably provided with a locking element matched to the interlocking element of the sampling device, wherein at least one detection zone of the sampling device, inserted into the reader, has a uniquely defined and blocked spatial position relative to the reading unit.

The carrier receiving assembly is preferably provided with a button for starting the reading of at least one detection zone of the sampling device introduced into the reader.

The sampling device housing is preferably provided with a pin constituting an internal positioning element associated with the corresponding carrier positioning element, the detection zone inside the sampling device housing having a clearly defined spatial position relative to the interlocking element of the sampling device. The internal positioning element of the sampling device housing is preferably a pin or projection inserted into the hole or dent in the carrier, the detection zone being on the carrier in a predetermined position relative to the hole or dent.

The source of scattered electromagnetic radiation is preferably a source of optical radiation, more preferably visible light.

The light source is preferably a pulsed light source. The carrier sheet is preferably a nitrocellulose carrier with a thickness not exceeding 1 mm.

The detectable material is preferably a direct molecular label.

Generally, the reader is a relatively durable unit that the user can reuse (and which may be equipped with an electronic memory / data processing circuit that allows evaluation of the results of many subsequent tests), and the sampling devices are intended for single use only after which they are discarded. Accordingly, sampling devices may be provided to the user separately from the reader, e.g. in the form of multiple packaging.

By ensuring accurate interlocking between the sampling device and the reader and ensuring the exact positioning of the detection zone within the sampling device itself, the detection zone is set relative to the reader in a fixed predefined position each time the sampling device is inserted into the reader. In this way, the design of the optical system inside the reader (light source and sensors) can be maximally simplified, since it is not significant for the sensors to contain any analysis unit, for example, which might be needed in a situation where the exact location of the detection zone would not be known. By avoiding the need for a complicated optical system, the reader / monitor cost can be reduced. The simplification of the optical reading system can in various ways allow minimizing the size of the reader / monitor, which supports convenient and trouble-free use at home. Of course, if necessary, an analysis team can be used in the reader.

An additional advantage of using an internal setting system that ensures precise placement of the detection zone inside the tested device is the possibility of facilitating automated and high-performance production.

In principle, any electromagnetic radiation can be used to measure radiation attenuation according to the invention. Electromagnetic radiation should preferably be able to undergo scattering. Preferably, electromagnetic radiation is light in the visible or near visible range. This includes infrared and ultraviolet light. It is generally estimated that the detectable material used as the marker in the sample is material that will interact with light in the visible or near visible range, for example by absorption. The wavelength of the selected electromagnetic radiation is preferably equal to or close to the wavelength which the marker strongly affects, e.g. by absorption. For example, if the tracer is a substance that is highly colored, it is visible to the naked human eye with compacted material, then ideal electromagnetic radiation is light of complementary wavelength. Ideal examples are molecular direct labels, for example colloidal metallic solutions (e.g. gold), elemental materials (e.g. selenium, carbon), dye colloidal solutions and dyed latex (polystyrene) particles. For example, for blue-colored latex particles, ideal electromagnetic radiation is visible red light, which is strongly absorbed by blue-colored particles.

In a preferred embodiment of the invention, the transmitted electromagnetic radiation reaching the sensor (s) should be diffused. This scattering may arise as a consequence of the transmission of electromagnetic radiation through a strip or carrier sheet, however, more preferably it is caused by an electromagnetic radiation source emitting energy in a highly dispersed form. In a preferred embodiment of the invention, the source produces highly diffused radiation, and the carrier strip or sheet through which this radiation is transmitted is, under comparable conditions, a much weaker diffusing agent.

The main advantage of using scattered light or other radiation in the context of the invention is that the reading of the test result is much less distorted by distortion or contaminating material on the sampling device. For example, dirt or scratches on the sampling device in the area through which radiation must be transmitted can strongly interfere with the accuracy of the result determined if focused instead of diffused light is used. By using a diffused light source according to the invention, it is possible to obtain a test result reader that can accurately interpret the results of tests carried out even in a substantially transparent test device6

178 125 without adversely affecting the sampling results, caused by slight contamination or damage to the sampling device (e.g. surface scratch).

In a preferred embodiment of the invention, the electromagnetic radiation from the source is pulsed. By synchronizing the sensors so that they operate only in phase with the pulsed radiation source, it is possible to eliminate any background interference that could be caused by external radiation, e.g. ambient light. It is estimated that tests will mostly be carried out under natural daylight conditions, or even more often artificial light. Artificial light is usually pulsating (typically 50-100 Hz) due to the alternating nature of electricity sources. By placing a pulsed radiation source for illuminating the sampling device inside the reader, the effect of natural daylight can be ignored. By adjusting the pulse frequency so that it is sufficiently different from the artificial light present, any disturbance due to this artificial light can also be ignored. Preferably, the energy pulse frequency should be at least about 1 kHz. The ideal pulse frequency is about 16 kHz.

The use of pulsed light is very advantageous in that it allows the monitor to bypass the "light tightness" feature. This not only simplifies the design of the monitor, but also the ability to read test results with the monitor in the "open" state, which simplifies user operations.

A light source or other electromagnetic radiation may be entirely conventional elements. Ideal examples are commercially available LEDs, preferably selected so that they emit light of the appropriate wavelength, which is strongly absorbed by the detected compacted material in the test zone (s). The light emitted by the LED should be passed through a strong diffusion unit before reaching the sampling device. If necessary, a number of LEd diodes can be used, which are supplied in turn. Suitable dispersing elements can be made, for example, from commercially available plastics. If desired, the light scattering properties of the scattering material can be enhanced by including molecular materials such as titanium dioxide and boron sulfate. The ideal scattering material contains polyester or polycarbonate containing titanium dioxide. A suitable level of inclusion for the particulate material is at least 1% by weight, preferably about 2%. By using a dispersing agent, all relevant areas of the sampling strip can be measured simultaneously, and differences in the level of light emission from the source are eliminated.

The sensor (s) for detecting outgoing light may be conventional elements such as photodiodes, e.g. silicon photodiodes.

Preferably, a second scattering element is located in front of the sensor (s), which can be made of the same material as the main scattering element. This ensures that the view received by the sensor is not disturbed by the presence or absence of a test strip in the read head. Consequently, you can calibrate the monitor in the absence of the test strip and then measure the test results in the presence of the sample strip.

By using the uniform light source according to the invention it is possible to obtain a reading system for test strips and the like which is relatively tolerant to changes in the position of the test zone / zones between successive strips in the absence of the analyzing sensor. In the present invention, the test reading device and associated sampling device can provide accurate quantitative information about the sample.

Devices of this kind can be used in a variety of places, such as hospitals, clinics, doctor's offices and at home. The analyte being tested may vary widely depending on the circumstances. Examples are organisms with an infectious disease or markers, metabolic products in body fluids that are indicative of changes in the patient's health or condition, and substances that are being distributed or taken, such as medicines or drug abuse.

To increase the likelihood of the concept, sampling devices have been labeled, which allows the user to monitor the urine concentration of lutenizing hormone (LH), which increases rapidly by approximately 1 day before ovulation. When daily testing of LH concentration in urine is carried out, for example by the use of "dipped rod" technology, with sampling results by the colored endpoint, the intensity of the color is proportional to the LH concentration. By providing the user with a color scale that allows the comparison of daily measurements against the standard value, one can simply detect the "LH stroke" by eye. However, monitoring of LH concentration is a very rare example of sampling based on semi-quantitative data, which is subject to such a simple technology, it is possible only because in relative concentration conditions the LH jump is a drastic case. For most other potentially useful assays, changes in analyte concentration in body fluids are much smaller and can only be accurately detected by appropriate instruments.

There is therefore a need to extend the currently available qualitative testing technology for home use to the area of ​​precise quantitative testing. A preferred example, which logically extends existing consumer interest in pregnancy testing for home use and ovulation cycle testing, is to closely monitor the ovulation cycle, not only to increase the likelihood of a concept but to obtain reliable information for contraception. Therefore, body fluid analysis was proposed. A common goal is to monitor the periodic fluctuations of various levels of hormone metabolites in urine.

The invention can be used to determine any body fluid analyte, especially when monitoring a human ovulatory cycle by determining one or more hormones or metabolites in body fluid such as urine, for example either LH and / or estrone-3-glucoronide (E3G).

The home sample fluid testing device comprises a porous support material, such as a strip through which an applied fluid sample such as urine can penetrate and in which the result of the test is manifested by specific binding of detectable material in a precisely defined area (detection zone) of the support, such as a narrow line or small dot containing immobilized specific binding reagent. The invention therefore relates to methods by which the location of detectable material in such a detection zone can be determined in a simple and cost-effective manner. The inventive test reader is useful, especially for testing body fluid samples at home, and combines the convenience of testing a sample with a simple and cost-effective digital determination of the test result. Transmission spectrophotometry is a technique widely used to quantify dye concentration in transparent liquid solutions. Commercially available spectrophotometers usually require significant modification for measuring dispersed solutions. Transmission spectrophotometry is not an appropriate way to measure highly dispersed samples because it is generally only adapted to cases where alternative solutions cannot be used. For the purposes of the invention, the measurement of transmission gives positive advantages over the previously used more frequently reflection phenomenon, applied to test strips.

Chemical phenomena of the recommended strip devices according to the invention occur throughout the entire thickness of the test strip. Due to changes in reagent flow and deposition, the concentration of the detectable tracer captured at the reaction zone may vary according to depth.

Curvature, surface materials, finish and solvent influence can change the mirror to diffuse reflection ratio. For reflectance measurements, the reflected light from the strip surface carries information about the signal (that is, the light will work with a detectable marker), while it is reflected in a mirror

178 125 will not contain information (because this light is the component that just bounced off the surface without interacting with the detectable marker in the diffusion strip). Without the use of relatively massive and expensive systems, it is difficult to design a reflection measurement system that minimizes mirror reflection to the extent possible with transmission measurement using diffused light as per the invention.

Measuring systems require the use of a test surface that must be removed from the optical path for calibration. This reference surface must not be damaged if it is to form part of an optical assembly. In addition, mechanical movement is desirable for displacing such reference material when the sampling strip in turn needs to be measured. There are no such problems in the reader according to the invention.

In addition to the specific examples of detectable materials according to the invention already mentioned, materials which block or reflect electromagnetic radiation instead of absorbing them may be used as tracer materials, e.g. "white" particles such as latex particles in their natural, unstained state. Alternatively, the label may be a reagent or catalyst that is involved in the production of radiation absorbing material or radiation blocking material, e.g. an enzyme which reacts with a substrate to produce a detectable material, such as a colored material, in the detection zone.

The object of the invention, in an embodiment, is shown in the drawing, in which Fig. 1 shows a general view of a sheet of porous material, e.g. paper, during the deposition of the reagent on the sheet and dividing the akrusik into sampling strips, Fig. 2 - exploded view of the device sampler according to the invention, comprising a sampling strip as shown in Fig. 1, Fig. 3 - a schematic cross-sectional view of the sampling device of Fig. 2, positioned inside the reading head of the monitor according to the invention, operating by transmitting light through the sampling strip, the y axis being distorted to show the arrangement of the components, Fig. 4, Fig. 5 and Fig. 6 show, partially exploded, the main components of the complete of the monitor according to the invention, Fig. 4 shows the lid and upper half of the housing, Fig. 5 - the electronic circuit board containing the read head, Fig. 6 - the lower half of the housing and the attached container with the battery, Fig. 7 - enlarged reading head shown in Fig. 5, Fig. 8 - top view of the reading head of Fig. 7, including the receiving slot of the sampling device, Fig. 9 - cross-section of one the end of the sampling device designed to be inserted into the receiving slot of the read head, while fig. 10 presents in schematic form the main functions that may be desirable for the electronic monitor used according to the invention, used to monitor the ovulatory cycle in humans.

As shown in Figure 1, a sheet 100 of porous material, e.g., nitrocellulose, is intended to be divided into a plurality of identical sampling strips constituting the carrier sheets 101 by cutting along the central AA axis and lateral BB axes.

Parallel lines constituting the detection zones of 102-107 sampling reagents are placed on the sheet 100 before it is divided. Only for the examples it was assumed that the reagents constituting the first immobilized antibody are arranged in lines constituting detection zones 102 and 107, and the second different immobilized antibody is arranged in lines constituting detection zones 103 and 106. The reagent can be deposited using a pen 108 or similar via a computer controlled XY recorder (not shown) and fed with a suitable buffered reagent solution via a measuring tube 109. If the sheet material 100 is nitrocellulose, then reagents such as antibodies and an antigens can be immobilized by simple direct application to nitrocellulose followed by blockage of the sheet material, for example with albumin or polyvinyl alcohol. After reagent deposition and blocking, two lines 104 and 105 of mobile marker reagent such as an antigen (e.g. E3G) or other antibody (e.g. anti-LH), labeled for example with a direct molecular label such as stained latex. This embedding can be done, for example, with the next pen

178 125 (not shown). Alternatively, the labeled reagent (s) may be stored in a separate porous pad or similar instead of being applied directly to the test strip material.

For precise placement of reagent-containing lines, each longitudinal rim 110,111 of sheet 100 is punched with numerous identical small holes 112 each of which is positioned within the width of marked strip 113. Holes 112 are made in sheet 100 prior to deposition of any reagent. The raw sheet is placed on a frame (not shown) or similar work surface by means of a crossbar 114 pressed down on each side of the sheet. The figure shows (partly) only one of these crossbars. Each crossbar has a plurality of dowels projecting downwards 115, each of which falls exactly into one of the holes 112. The movement of the reagent embedding pen 108 is precisely aligned with the position of the sheet holding crossbars, and accordingly the deposition of the reagent is carried out according to a predetermined precise line relative to the perforation in the sheet.

After all the necessary reagent deposits and other sheet treatments, this sheet is divided by means of a cutting unit (not shown) into individual identical strips constituting the carrier sheets of the carrier 101. Each individual sheet therefore contains one positional hole 112 with two lines containing the reagent or detection zones (e.g. .

102 and 103) positioned at precise predetermined positions relative to the aperture 112 extending across the width of each strip. In a position remote from the aperture 112 there is an area (e.g., area 104) of the strip containing the movable tagged reagent. The exact position of the labeled reagent relative to the aperture is not necessarily as critical as the location of the reaction zones.

For example only, individual strips will typically have a length of about 40 mm to about 80 mm, and a width of about 5 mm to about 10 mm, as is conventional in known sampling devices. A detection zone containing a reagent, such as detection zones 102 and

103 they will usually form a line about 1 mm wide, running sideways across the strip. Alternatively, a small spot, e.g. round with a diameter of about 1 mm to about 3 mm, can be used. The detection zone is therefore only a relatively small part of the total strip surface. If it is needed for a given sample, then many detection zones containing the same or different reagents may be placed on each strip. This may require the use of more than one marker component, a plurality of movable marker components may be positioned up on a strip or anywhere within the device (e.g., in a pad or on a absorbent sample supplying string, as described below).

As indicated in Fig. 2, the sampling device of the invention includes a plastic housing having upper and lower halves 200 and 201 adapted to contain a sampling strip constituting the carrier sheet 101 and also a member containing a paper sample 202 that can protrude from one end 203 assembled housing. In an assembled device, the paper receiving member 202 covers the sampling strip end 204 adjacent the embedded labeled reagent. The upper half of the housing 200 has a window or opening 205 through which both detection zones 102 and 103 can be viewed from the outside of the housing. The upper half of the housing has on its outer surface 206 a circular recess 207 on the central longitudinal portion of the available housing a short distance away from the viewing window relative to the end 203 of the housing receiving the member containing the sample. The inside of the upper half of the housing has a downwardly projecting pin or plug 208 located immediately below the recess 207. The diameter of the downwardly projecting plug or plug 208 is matched to the diameter of the hole 112 in the sampling strip, so that the strip can be forcibly placed inside the assembled pivot devices.

The lower half 201 of the housing also includes a light transmission window 209 or opening that, in the assembled device, lies directly opposite the result window 205 in the upper half of the housing. The lower half of the housing also includes recesses 210,

178 125 that can receive the bottom end of the pin or spigot 208 when both halves of the housing are placed together to form a closure.

In an assembled device, closing the strip and the paper member between the upper and lower halves of the housing causes the covering parts 204 and 211 of the belt and the paper member to be constrained to provide a reliable moisture conductive connection.

It is generally assumed that the housing material will be opaque, e.g. white or colored plastic, however, if desired, the housing may be transparent or substantially transparent.

Figure 3 shows the sampling device 300 positioned inside the slot 301 in the monitor 302. This area of ​​the sampling device includes two opposite windows 205 and 209.

The monitor housing has a slot to accommodate a portion of the sampling device containing result view windows. On the opposite sides of the slot there is a light source 303 and a reading head 304. The slot includes a button or projection 305 that can be fitted to a recess 207 on the outer surface of the device housing. In this way, precise positioning of the housing inside the gap is obtained. Because the recess is in a fixed position relative to the inner pin or spigot 208 inside the sampling device, and thus the positioning hole 112 in the sampling strip, so the two detection zones 102 and 103 on the strip are positioned in an exact position relative to the read head. Thus, the hole in the sampling strip acts as a forcing element in the production of the sampling device and ensures that after using the device and exposing it to the monitor, the detection zones on the strip will always be in the same position relative to the read head. Thus, there is no need for the read head to include an analysis unit for placing detection zones in each inserted device.

The light source or illuminator 303 includes a plurality of LED lighting elements 306 for producing light that illuminates the sampling strip through diffuser 307 and observation window 209 in the lower half of the sampling device housing. The light passes through a thin nitrocellulose carrier sheet 101 and exits the sampling device through the result window 205 in the upper half of the housing. Directly outside the result window 205 is a second diffuser 308. After passing through diffuser 308, the light meets a plate 309 having a plurality of holes 310-314. There are a total of five holes, of which two (311,313) are in the vicinity of the detection zones and the others (310,312 and 314) are in positions on each side of these holes of the detection zones. The holes are in the form of slots corresponding to the detection lines on the strip. The width of each of the holes 311 and 313 corresponding to the detection zones is twice the width of each of the other three holes that perform control functions.

Light passing through these apertures goes down the corresponding slot 315-319 in the partition plate 320. At the distal end of each slot there is a light sensor 321. Sensors 321 have the same size and parameters. At the front surface 322 of the partition plate 320, each slot has the same size as the corresponding opening. At the rear surface of the partition near the light sensors, each slot has the same size as the adjacent light sensor surface. Thus, the two slots (316,318) accompanying the detection zone openings have parallel sides. The three slots (315,317 and 319) accompanying the control holes increase in size as they approach towards the light sensor.

The slit in the monitor may also accept a gripping or deflecting assembly, such as one or more resilient plates or pins (not shown) to further improve the forced location of the sampling device within the slit.

Ideally, the same optical signal comes from each hole regardless of the positioned linear position opposite the holes. The holes may have a variety of sizes to fulfill this purpose. The dimensions of the reference zone should be chosen so that they correspond as closely as possible to the current surface of the detection zone on the strip.

178 125

To reduce the possibility of interference between the holes, the sampling strip should be held as close as possible to the holes when the sampling device is placed in the slot in the monitor. As described above, five optical measurement channels were used in the reading device. In addition, a sixth electronic reference channel can be used to calibrate the electronic gain in the detector circuit.

A typical test strip may show a concentration gradient of the detectable tracer along its length relative to which the detectable tracer at the reaction zone is measured. To accommodate this, measurements are made ideally on each side of the reaction zone on the test strip. The signal from the reaction zone can be expressed as the ratio of the total signal recorded from two adjacent reference surfaces on the strip.

The five measuring channels are divided into two reaction zones and three reference zones. One reference zone sandwiched between two reaction zones provides an optical reference measurement for both reaction zone measurements.

The reflectance measuring system must be mounted on one side of the test strip. To obtain the same level of content for a five-channel reading device, relatively expensive components would be needed. The transfer solution can be designed as a whole with high-volume optoelectronic components commercially available, facilitating the production of a monitor that is compact and relatively inexpensive.

Five sensors 321 are mounted on the rear surface of the partition plate. Each sensor receives an image of the test strip through a hole in the partition. The baffle prevents the light seen through one opening from entering adjacent sensors, as well as provides adaptation to line tolerances. The position of the test zone within the sensor view field may vary from one hole edge to the other on the x axis. Any signal change resulting from this effect is a function of the angular displacement relative to the center of the sensor. The partition depth can be selected to control the possible angular displacement of the test zone relative to the sensor and to maintain reading accuracy.

The projection 305 is held in an exact position relative to the holes. The reference pin enters the recess 207 in the sampling device housing. This recess is also positioned precisely relative to the inner circle formed in the sampling device on which the test strip is positioned through its own position hole pierced by the strip. The reaction zones are exactly positioned or positional hole. In this way, within the manufacturing tolerance, the reaction zones are held in exact positions relative to the holes through which the sensors receive an image of the test strip.

The illuminator may consist of a number of LED elements mounted or placed on the scattering medium, which gives uniform and diffused illumination of the test strip covering the reference and signal zones. The introduction of a diffuser between the holes and the test strip is beneficial for calibration. To calibrate each of the optical channels in the absence of the sampling device, it is desirable for each sensor to collect light from the same illuminator spaces as in the case of the sampling device. The diffuser can be selected so as to be the dominant diffuser in the optical path, so that importing the test strip has no significant effect on changes in the distribution of lighting observed by the sensors. In addition, the diffuser may allow the use of an "abrasive cleaned" surface in the optical system desired for long-term, repeatable operation of the optical assembly. By modulating the intensity of the illuminator, you can calibrate the optical channels, without the help of moving parts, invisibly to the user before inserting the sampling device.

The test strip may consist of an optically dispersed nitrocellulose layer or the like preferably sandwiched between two layers of optically pure film, e.g. a polyester such as mylar. A clean film protects nitrocellulose inside which sampling reactions occur. Measuring reflectance through thin transparent fil12

178 125 my is particularly difficult due to the problems arising as a result of mirror reflections. Transmission measurement enables an optical system perpendicular to the measuring surface and minimizes the negative effects of reflection.

The invention is particularly useful for reading test strips made of nitrocellulose and similar scattering membranes, which preferably do not exceed a thickness of about 1 mm.

Returning to Fig. 4, the monitor includes a molded housing, e.g. of plastic, having a generally oval rounded shape. The housing mainly comprises an upper half 400 and a lower half, with only the upper half shown in Fig. 4. On the right side of the housing 400 is a recess 401 having a backward sloping rear surface 402. The back surface 402 includes a button opening 403 (not shown), a window 404 for exposing the viewing panel (not shown) and two windows 405 and 406 for exposing colored lights or other indicators (not shown again) to provide information to the user. A long slot 407 extends from the left end of the recess 402 to allow access to the read head (not shown). The recess 401 and the gap 407 are closed by a lid 408 which is attached to the back of the housing by two hinge points 409 and 410. The upper surface 411 of the housing 400 is slightly depressed for receiving the lid after closing, so that the external of the closed device forms a relatively smooth continuous surface . The lid can be tilted up to reveal user-accessible monitor components. The lid is closed with a spring clip (not shown in fig. 4) which extends up through the opening 412 in the front edge 413 of the housing. The front edge 413 of the housing includes the next opening 414 through which the next indicator light (not shown) can be observed.

The circuit board 430 shown in Fig. 5 has a rounded rectangular shape to match the internal shape of the housing, and includes all monitor operating elements. They include a button 431 that can be pressed by the user to initiate ovulation cycle monitoring. When the circuit board is mounted inside the housing and covered by its upper half, the button is accessible through hole 403. To the right of the button is a visible display panel 432 such as a liquid crystal display that is visible to the user through a window 404. To the right of the display panel are two light guides 433 and 434 that transmit, for example, colored light (such as red and green ) two LED elements or similar lights (not shown). Appropriate semiconductor "chips" and memory circuits 435.436 are mounted on the printed circuit board. The next light guide 437 mounted at the front edge 438 of the circuit board can lead the light from the next LED light element (not shown) to the opening 414. This light may, for example, indicate to the user that a test is needed. This light may have a different color from the lights accompanying the display panel, e.g. yellow. The battery connector 439 hangs from the bottom of the circuit board for connection to batteries held in the bottom housing (see Fig. 6). At the front of the circuit board is a switch 430 actuated by the spring clip 408.

A reading head 441 is mounted on the left side of the circuit board which includes a central receiving slot 442 receiving one end of the sampling device (not shown). There is a light source 443 at the front of the receiving slot 442, and an optical sensor system 444 is directly opposite the back of the slot so that light can be passed across the slot (and through the sampling device when it is inserted) and evaluated using the sensor.

The lower half 460 of the housing shown in Fig. 6 has an overall oval shape to fit in the upper half 400 and provides room for the circuit board 430. The front edge 461 of the housing 460 is provided with a spring clip 462 to secure the lid 408 after closing. Hook 462 is released by pressure on the front surface 463, e.g., by the tip of a finger. The bottom of the housing 464 contains a battery compartment (below) and a small opening 465, which is located near the right end of the housing through which you can release the battery connector 439 and connect it to the battery 466. The batteries are held by the cover 467, which can snap on to the underside of housing 468.

The essential parts of the housing may be formed of impact resistant plastics or similar plastics such as polystyrene and polycarbonate, the parts being held together by means of hooks or threaded screws or by any other suitable mechanism.

Returning to the enlarged view of the reading head shown in Fig. 5, it can be seen that the receiving slot 442 for the sampling device room is in the form of a parallelogram, however, its width is enlarged at the right end 500 in a graduated manner to obtain a pair of arms or projections 501.502 to which it may adhere. appropriately enlarged part of the sampling device. This may facilitate the efficient insertion of the sampling device into the reading head. Within the narrower working portion 503 of the slot there is a button 504 mounted on the rear wall of the slot 505 that must be fully depressed to activate the reading mechanism. Inserting the sampling device properly will lower this button properly.

Also on the back wall 505 of the slot is a fixed position pin 506 that attaches to the corresponding hole in the inserted sampling device. On the back wall 505 there is also a light transmitting panel 507 that includes optical sensors. Panel 507 projects outwardly beyond the plane of the rear wall 505 of the gap and has sloping edges 509 to give it a distinctive profile. At the opposite ends of the front gap wall 510 there are two pins (not shown in the figure) which are deflected outwardly towards the gap, e.g. by means of spring mechanisms contained inside the two housings 511, 512.

The same elements are shown in Figure 8, which is a view directly down into the receiving slot. Two deflected pins 600,601 are shown. The purpose of these pins is to provide biasing elements that push the inserted sampling device relative to the back wall 505 of the gap. If the received portion of the sampling device has appropriately shaped holes or recesses to receive a fixed position pin 506 and protruding panel 507, then the sampling device may be pressed close enough to the rear wall of the slot to press the button 504 and initiate the optical sensing procedure.

Figure 9 shows a portion of the sampling device 700 having a profile cooperating with the elements shown in Figure 8. The sampling device can be inserted into the slot so that the wider central portion 701 adjoins the projections 501, 502. The leading end 702 of the sampling device has a slightly beveled edge 703 to facilitate insertion into the slot beyond the pin 600. The sampling device includes a hollow housing having a porous sampling strip 704 sandwiched between two sheets of transparent material 705, 706.

As described above, the strip 704 is positioned precisely inside the sampling device housing by means of a pin 707 which passes through the opening 708 in the strip. Outside the sampling device housing, at a location corresponding to the center of the position pin 700, there is a conical hole 709 that can receive a fixed position pin 506 in the reader slot. Each side of the sampling device housing has an opening 710, 711, which after properly inserting the sampling device into the slot will be in the vicinity of the light source 443 and light sensors 444, respectively. The profiles of these two holes are different, in particular the profile of the hole 711 on the same surface of the sampling device every tapered opening 709 is shaped to match the profile of the projecting panel 507 including the light sensor. This ensures that the read head only works when inserted correctly to ensure that button 504 is pressed.

For example, only the basic functions that may be required in the monitoring device are indicated in Fig. 10 and briefly described below. Individual features may be entirely conventional, and electronics professionals may use other combinations and distributions of such features to achieve the purposes of the invention. For example, systems with

178 125 built-in software and neural networks instead of conventional microprocessors based on semiconductor technology.

As shown in Fig. 10, such a combination generally includes a reading unit 800 for receiving information from a sampling device such as a sampling strip, the reading unit comprising a light source 801 and a sensor 802 (shown here as a photodiode). The reading unit gives a signal to the processing unit 803 to convert the optical signal into a usable form for the microprocessor 804. As a feature of the calibration, the 805 calibration system was used to transform the signal from the reading unit into data corresponding to, for example, an absolute concentration value.

A timing element, such as a 806 clock, may also be needed to regulate the measurement within a cycle. The 804 microprocessor processes, stores and interprets the result in the light of previous results, in particular those recorded from previous cycles. The distribution board 807 provided to the user generally includes at least such elements as a button that the user can actuate at the start of the cycle to initiate operation of the entire device. The 808 power source should contain components such as the 809 redundant memory capacitor to avoid losing data from the past when battery replacement becomes necessary.

Information can be given to the user by means of a display working on the basis of liquid crystals or LEDs. If necessary, information on fertility status may be given by a simple visual indication, e.g. a color combination showing for example green for infertile days and red for fertile days. In particular, if the device is intended as a contraceptive aid, it should show a "fertility" signal in the event of damage.

As described above, items 803 and 806 together correspond to item 435 (Figure 5), and item 804 corresponds to item 436 (Figure 5).

A double analyte testing device, selected by chance from a series of identical devices as described above with reference to Figures 1 and 2, using blue colored latex particles as a concentrated marker on two test lines on a nitrocellulose strip to estimate the test result, inserted repeatedly and read in a monitor made as described above with reference to figures 3 to 10.

The intensities of the two test lines represented LH and E3G, respectively, in the urine sample applied to the sampling device.

The sampling device was inserted and removed from the monitor ten times. The percentage light transmission for each reading is shown in the table.

Table

<td rowspan="7"></td><td>LH</td><td>E3G</td><td>LH</td><td>E3G</td>

<td> 44.0</td><td> 39.3</td><td> 43.9</td><td> 39.4</td>

<td> 43.8</td><td> 39.3</td><td> 43.8</td><td> 39.2</td>

<td> 43.8</td><td> 39.5</td><td> 43.9</td><td> 39.2</td>

<td> 43.8</td><td> 39.3</td><td> 43.9</td><td> 39.2</td>

<td> 43.8</td><td> 39.3</td><td colspan="2"></td>

<td colspan="2">LH</td><td colspan="2">E3G</td>

<td>Average:</td><td colspan="2"> 43.9</td><td colspan="2"> 39.3</td>

<td>sd:</td><td colspan="2"> 0.1</td><td colspan="2"> 0.1</td>

<td>cv.</td><td colspan="2"> 0.2%</td><td colspan="2"> 0.3%</td>

These results indicate that the reading system of the invention allows obtaining significant data that was not significantly affected by the variability of the test line arrangement when the sampling device was inserted into the monitor.

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Fig. 2

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<img file="PL178125B1_D0003.tif" />

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430

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Fig. 5 ο

439

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Figure 6

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Fig. 7

512

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Fig. 8

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706

Fig. 9

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<img file="PL178125B1_D0009.tif" />

Fig. 1

UP Department of Publications. Circulation of 70 copies

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