DE3612873A1 - SYSTEM FOR THE MULTIPLE AND SIMULTANEOUS DETECTING AND MEASURING OF CHEMICAL AND IMMUNO-SEROLOGICAL REACTIONS IN SOLID AND LIQUID PHASE - Google Patents

Description

- * 5. April 1986 P 9864-reeb

Paolo PRANDINI, V.le Europa 72 / G, Brescia

System for the multiple and simultaneous detection and measurement of chemical and immuno-serological reactions in solid and liquid phase.

The invention relates to a system for the multiple and simultaneous detection and measurement of chemical and immuno-serological Solid or liquid phase reactions.

For all analysis devices commonly used in laboratories the chromatic measurements are carried out with the classic system of the light beam, which is with a Photo duplicator or a photodiode is coupled, with an analog recording of the signal afterwards follows.

Recently, optical fibers have been used to increase the number of emitting and / or sensory elements in Systems with multiple readings, but generally a purely mechanical scanning is used, which may be servo-controlled by a processing device, even if only a limited ability of self-

Correction of incorrect positioning, etc. is available.

In practice, every instrument or device requires a very precise setting or positioning of the sample or test piece under test, with problems of a mechanical nature and consequently also of reliability. The use of the processing device in those cases in which it is used has generally remained at the final data processing level as an aid in handling operations that would otherwise have to be carried out manually.

"." ..- 'In the traditional approach, one pre-occupies itself the execution of the measurements so as to optimize the number and quality of the information with one more or less mechanical or hand-carried procedures, which are consequently in terms of time and the cost is expensive, also at the expense of flexibility and adaptability and the security of the system.

On the other hand, the possibilities opened up by the advent of microprocessors allow one analyze and classify and discriminate large amounts of information in extremely shortened times, what advantages in terms of precision

and versatility in use.

The present invention provides that you have a telecamera or television camera or the like. Device used to record the data of chromatic absorption or emission and shape a suitably treated or even raw pattern or test piece in block or partial images record by exposing the test piece or pattern to a light source if necessary, and that the information obtained or recorded in this way is stored in a memory area of a Computing and processing device stores, which then eliminates the unnecessary data in this way Averaging or filtering data and, in general, this data, as dictated by the various needs requires further processing.

In this way, the operator transfers the task of filtering and comparing to the computer system, that the calculations using certain mathematical process steps and executes a suitable program which is adapted to the various requirements.

It is therefore the aim of the present invention to provide the integrated use of an image reader and a computing and processing equipment for the purpose of

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qualitative and quantitative multiple (not only in terms of the number of samples and test pieces, but also in a very tight time frame) and simultaneous determinations to carry out in the field of analyzes, in the technique of chemistry, attenuation measurement and Color measurement, serology and immunology can be done.

Compared to the state of the art of today, such a system has the advantage that by using a Range of for applications in other, different Uses already known terms and techniques in areas, practically within a real, reasonable time carries out a set of determinations on several samples and test pieces, possibly in the data to be processed identifies and corrects existing errors or malfunctions. The invention is limited Incidentally, not just counting the elements or identifying shapes, but permitted In addition, a quantitative analysis of the color measurement (kolorimetrisehe), whereby one inhomogeneity or Detects asymmetry and various errors based on a formal description of the type of preparation under examination corrected.

Further advantages of the subject of the invention result from the following description made with reference to FIG

the only figure of the drawing has been taken which is a block diagram of the system.

The system according to the invention essentially contains a light source 1, a receptacle 2 for the pattern or the sample, a scanning and sensor device 3 for scanning and measuring or recording the image, a control circuit 4 for converting the data coming from 3, a read / write memory 5, a 6 microprocessor, peripheral components such as one Keyboard 7, a display device 8, a diskette memory and printer 9 and carrier and supply circuits 10.

The system can be used industrially in all areas of analysis in which the measurements are via qiintitative or non-quantitative analyzes of the variations or changes in the color and appearance of a Illustration, which can also be composed of several characteristic parts, can be carried out.

In more detail, the light source 1 can consist of any lighting system (lamps, solid-state photo emitters etc.) that may, but not necessarily, be uniform or even and stable in the measuring range. The light source 1 can be equipped with chromatic filters or other systems for selecting the wavelength.

The receptacle 2 for the sample or specimen or for the support of the pattern or specimen is provided between the light source and the scanning and sensing device and can carry any liquid or solid substances or materials.

The scanning and sensor device 3 for continuous or selective scanning and measurement or recording of the image of the preparation under examination by means of Reflected or transmitted light can be a television camera with a tube or a solid-state element (e.g. CCD) with a system of appropriately sized and depending on the area or the type of measurement positioned lenses is coupled.

The control circuit 4 for controlling the device 3 allows the processing device the signals of a entire image or just a part of it, in order to then store it in a suitable memory to file later processing.

To be clear, the precision with which the data has to be digitized or converted into numbers depends on to a large extent on the application both in terms of the study of the intensity and the form.

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For the sake of simplicity and convenience, can operations can be carried out in the analog state of the signal (e.g. by using a low-pass filter, to avoid the problem of frequency mapping).

The read / write memory (e.g. semiconductor RAM is used either for normal processing of the operations of the processing device or of the original data and the final results or to receive intermediate results of the processing operations as a digitized image; accordingly it contains Data and programs.

The microprocessor 6, which can consist of several micro-programmed parts, is the core of the system: That The program that controls and controls it fulfills a whole range of tasks, from dialog with the peripheral devices, to computing and "talking" to the human operator.

The series of peripheral devices 7, 8, 9 has the task of facilitating interaction with the user and to submit the final results or the application programs save. Typically, these peripheral devices consist of the keyboard 7 (capacitive, with contact closure, with Hall effect, etc.),

from the display device 8, e.g. a screen display with vector graphics or dot matrix, or even one Liquid crystal display, with plasma or with electroluminescence, from a thermal or laser printer 9, which can represent dots or whole characters, and from a floppy disk mass storage device (but it could also be a Bladder memory or any other magneto-electric or optical storage device).

It is clear that this set of devices mentioned above does not necessarily have to be in every case must be completely present.

The various carrier and supply groups obviously form an indispensable part of the system, e.g. peripheral controls, digital or analog time, filter or delay circuits, amplifiers, Voltage generators and power generators for correct operation of the basic components of the system and also used to interconnect the different types of logic systems that may exist.

APPLICATION EXAMPLE

Those obtained with the classic process on cellulose acetate make serial electrophoretic lines

individually like a series of bands with different chromatic intensities, but with the same fundamental tone (e.g. red) arranged in groups of several patterns on the same strip.

The acetate strip is laid out or spread out or applied to the pattern carrier, which consists of a glass strip is formed with suitable dimensions, which has a reference mark corresponding to the first Pattern is positioned; this bar is then inserted into the receptacle 2 of the device according to the invention.

The receptacle 2 is shielded from the surrounding air and is illuminated by diffuse light emitted by a white lamp fed with direct current is generated in such a way that that of the pattern or against a white The specimen, laid out in the background and surrounded by a joke frame, is reflected via a collecting lens reaches the sensor, which is formed by the component CCD type ICX 021-L from Sony.

The above sensor is used during scanning by the Computer controlled at a speed that is slower than that of a standard television camera, and the data of the matrix are transmitted via an analog-to-digital converter by Analog Devices with a resolution of 8 bits per point for a total of 290,000 points

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41

works in such a way that black corresponds to the value zero and the point most illuminated on average corresponds to the value at the lower end of the scale.

The mapping stored in this way is first normalized with respect to the possible local changes the intensity of the light source Ie previously established are; it then becomes the mean level of the intensity of the background and on that basis the dimensions and determined the number of rectangles that were being examined electro-phoretic gradients included. In a separate way you can recognize the reference mark that has the the first pattern is called and / they are used to create the to number individual lines or lines. From there on, one looks at the individual line, from which the axis of the measurement is calculated on the basis of homogeneity and symmetry considerations: only the data, which are arranged in line from a point (pixel) along this axis are used for the following Calculations used.

This set of values is digitally filtered using the moving average methods and the transformed and antitransformed speed according to Fourier used to calculate the components with a higher To eliminate frequency.

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For interpolation, the baseline is obtained through a straight line or a curve of the second order is represented and to which the other data relate.

The final graphic at this point is already in memory; the minimum values are then determined, on the basis of which the areas of the individual fractions are calculated, which are percentage-wise in relation to the total area can be expressed and / or in percentage grams with reference to the serum content of the total proteins.

The graphics and the data are displayed and made visible on the television screen 8 of the reader, with the operator is given the opportunity to prevent or adjust the minimum values before printing what happens with the help of the printer 9.

These. End frequency is used for each of the identified patterns or specimens repeated.

All processing operations are carried out in real time without external intervention, e.g. with help a microprocessor 32008 (version 32032 with 8 bit from National), the 512 kbyte memory RAM and the with a program provided EPROM 2764 of 8 kbyte.

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3612833

The advantages of the system described above, when applied to the method in question here, exist in this:

a) that the work takes much less time than that the conventional methods can be carried out;

b) that a considerable reduction in critical mechanical parts is achieved and consequently one greater reliability;

c) that greater precision is obtained due to the presence of the various reference marks of Zero and lowest scale value;

d) that a considerable reduction in interference is achieved by the noise floor;

e) that less manual labor is required, so that the operating costs are lower.

Claims (2)

April 15, 1986 Paolo PRANDINI, V.le Europa 72 / G, Brescia System for the multiple and simultaneous detection and measurement of chemical and immuno-serological reactions in solid and liquid phase. Expectations 1. System for multiple and simultaneous detection and measurement of chemical and immuno-serological Reactions in the solid or liquid phase, characterized in that a reader and a computer is used. 2. System according to claim 1, characterized by the integrated use of a reader and a Computer, for reading electrophoretic lines (on cellulose acetate, cellulose nitrate, etc.) from Sero-, lipo-, glycoproteins, hemoglobins, isoenzymes etc. and for the simultaneous qualitative and quantitative Measurements in the field of clinical chemistry, serology or immunology, e.g. on microplates with classic, Color measurement techniques or with the help of systems such as EIA, ELISA, etc.