DE2056291A1 - Device for differentiating, numbering and sorting particles according to their microstructure - Google Patents

Description

Dr. F. Zumsteln sen. ■ Dr. E. Assmann Dr. R. Koenlgsberger - Dipl.-Phys. R. Holzbauer - Dr. F. Zumsteln Jun.

■ "PATENT LAWYERS

TELEPHONE: COLLECTIVE NO. 225341 TELEGRAMS: ZUMPAT CHECK ACCOUNT: MUNICH 91139

BANK ACCOUNT: BANK H. HOUSES

8 MUNICH 2,

Cornell Aeronautical Laboratory, Inc., New York, USA

Device for distinguishing, counting and sorting Particles according to their microstructure

The invention relates to a device for recognizing various different microstructure particles in a fluid, especially for differentiation, counting, sorting and collecting of particles within a sample charge.

Since the main field of application of the invention in the testing of Blood, the use of the device will be described below with blood as the sample liquid. The invention However, it is common to identify and / or sort microstructures suitable.

In clinical practice, blood samples apply checked by type, amount and to determine properties of the variously designed elements contained therein. Blood is known to contain red cells, five main groups of white cells and platelets. Normally will take a small amount of total blood to one

109822/1752

Microscope slide painted, stained and observed around the Distinguish and count "blood cells".

Various devices are currently known which attempt to automate blood counting. With these devices it is generally possible to count the red cells and, by chemical solving, the total number of white cells. However, none of these known devices is able to distinguish the five basic types of white cells in a reasonable time still process all of these cells, including platelets, without using a second method. Further With the known devices, neither sorting nor preservation of the tested cells is possible.

Mach one of the known methods, a blood sample is diluted. To count the white cells, part of the sample is dissolved to destroy the red cells and pumped through an illuminated observation chamber with a black field. As a particle passes through the chamber, a photosensor records the forward scatter caused by the white cells. To count the red cells, the remaining undissolved sample is further diluted and pumped through the chamber. With this device it is not possible to differentiate between the cell types and the sample is destroyed during the test. Another known method is to use a conductive fluid to dilute the sample. As the fluid passes through the sample chamber, the conductivity of the fluid changes if cells are present. Because of the different size of the two types of cells and the resulting difference in the conductivity of the cells, it is possible to distinguish between red and white cells. In this case, however, the platelets cannot be counted reliably and the sample is also destroyed during the procedure.

109822/1752

'1 i | i7B P "Τ * ι | i | ι

The device according to the invention for detecting certain microstructure particles from a plurality of microstructure particles within a fluid is characterized by a line device containing a sample of the fluid with the particles, by an examination device for examining the microstructure of individual particles in the fluid and thus by a limited range passing fluid nalysis by means responsive to the examination means measuring or Nachweiselnrichtung, for generating an electrical output signal, and means for ^a and processing the output signal in order to derive a plurality of output signals, each corresponding to a single particular constituent of the sample .

If the sample fluid contains blood and the particles in the fluid form the Elements of the blood, so can with the device according to the invention all types of blood cells can be distinguished without chemical solution or staining. Furthermore, the cells are not destroyed during their detection or during their detection and they can If required, they can be sorted and collected for further analysis. In general, the invention relates to an apparatus for use with sample fluids, the microstructure particles included, which is the path length of exposure from a Affect exposure source. A sample of the fluid can be diluted and pumped through an observation chamber with microcapillaries so that the individual particles in the fluid flow essentially sequentially or one after the other. The microstructure each particle can be seen through fluoroscopic optics to be observed. A photosensitive device responds indicates the optical path length changes within a part of each observed particle and produces different ones indicative of the same Output signals. The output signal can be through a suitably programmed logic circuits are analyzed, which generates control signals. The control signals are applied to flow adjustment devices in accordance with the changing microstructure led to sorting and collecting.

109822/1752

If blood is used as the sample fluid, the invention is based on the fact that each type of blood cell is characterized by a microstructure with its own specific random pattern which does not change with regard to cell size or maturity. That is to say, the spatial distribution of the optical densities or the light densities of each of the microstructure patterns is specific for each type of cell. This allows the individual cell types to be identified by the differences in their micro tincture. It has been found that it is not necessary to observe or examine the complete microstructure of a given cell before identification can be carried out. Sufficient information for cell detection by examination or scanning consists in the fact that part of the microstructure contained in a narrow strip over a randomly aligned cell is sufficient if it passes through the line device, which can contain a micro-capillary tube.

Since the cell and its microstructure show essentially the same color and contrast, the microstructure will normally not be visible when using incoherent light. However, since there are small optical path length differences within the cell microstructure, a measuring device can be used which is responsive to such path length changes. the signal emitted by such a measuring device can, analyzed and processed in a suitable manner, be transformed in order to identify the particular type of cell which generated this signal. In this way, the device according to the invention distinguishes, counts, sorts and collects the shaped elements of the entire blood in a reasonable time.

109822/1762

Is the particle passing through the conduit device recognized, a separation can be achieved with the device according to the invention be made. This is done by means of suitable devices for controlling the particle flow by means of several flexible devices Pipes or hoses to several separate collection containers. The tubes can be connected by piezoelectric, electrostrictive or magnetostrictive elements are controlled by the preselected tubes are moved so that they are accordingly align with the control signal with the outflow side from the microcapillary tube.

The invention will be described in greater detail below with the aid of the preferred exemplary embodiments shown in the accompanying drawings explained. Show it!

Pig. 1 a schematic view of the device according to the invention, portions thereof being shown in block form; Pig. Figure 2 is a cross-section along line 2-2 in Pig. 1} Pig. Figure 3 is a cross-section along line 3-3 in Pig. Ij Pig. 4 is a more detailed schematic view of the signal analyzer the pig. 1, in which the conventional components thereof are shown in block form;

Pig. 5 the dependency of the relative power spectrum resp. Intensity spectrum from the frequency of different types of white blood cells;

Fig. 6 is a schematic functionality diagram of the method used in Pig. 1 shown Sorting direction;

Pig. 7 is a cross-section of the diagram shown in Pig. I shown sorting device j.

8 in a view similar to Pig. 1 shows a modified embodiment the device according to the invention; and FIG. 9 shows a section of the capillary passage in FIG. 8.

109822/1752

As already mentioned, the description refers to the application in the blood analysis. However, this is only done for the purpose of illustration and is not to be construed as a limitation of the invention.

There are 7 elements in human blood in the form of cells or cell fragments that are released from the spinal cord or other sources with the circulating blood. The elements are suspended in a saline plasma solution. The cells take up about 50 % of the total volume of circulating blood. The white cells or leukocytes are real cells with nuclei and active motility. They are the largest of the formed elements, their size ranges from 12 to 20 / u. There are five types of white cells, namely neutrophils, eosinophils, basophils, lymphocytes, and monocytes. The other elements of the blood are the erythrocytes (red cells) and the inrombozytes (platelets). The mean number of elements formed is ³⁰ mm of blood! "Zeil" types number

Erythrocytes 5.40 χ 10

Neutrophils · 4.40 10 ³

Boslnophlle 0.20 χ 10 ⁵

Basophils 0.04 χ 10 ^

Lymphocytes 2.50 χ 10

Monocytes 0.30 χ 10 ³

Platelets 250 χ 10 ³

The leukocytes have a neutral optical density, are very flexible and their spherical shape is easily disruptive. The erythrocytes (red cells) bind cell fragments without a nucleus. All red cells are roughly the same shape and size. They have the shape of a biconcave sole plate with a diameter of 7.2 ax and a thickness of 2.4 ax. They are very flexible and, because of their hemoglobin content, they look good

109822/1752

very close. The platelets are the smallest elements. you Diameter is about 2 yu, they contain a very dense one Grain.

The one in Pig. 1 includes a device shown schematically Sample container 10 having a conical lower portion around which a plurality of coils 11 of electric wires are wound, which work together with an internal impeller 12. The coils 11 are connected to a voltage source, not shown.

Next to the sample container 10 there is a container 13 sur Deliver a measured amount of undiluted blood to the container 10. For this purpose, there is a piston in sloh ia container 13 14. The delivery of undiluted blood takes place via an outlet Ib, which is in communication with the container IO. The blood is over an inlet 16 is introduced. Furthermore, a solvent container 20 is arranged next to the container 10, from which a measured Amount of a diluting fluid such as a saline solution can be introduced into the container 10. A slides inside the cylindrical wall of the solvent container 20 Piston 22 through which it dispenses the diluent from a Inlet 24 su a discharge 26 is controlled, which is connected to the container 10 is in change.

A piston 28 slides in the container 10 for dispensing the blood-diluent mixture by the lower konlaohen part 30 of the same in a molded thereon or attached in a suitable catfish cylindrical conduit 32. The pistons 14, 22 and 28 can geeij ^ eggs ^ geeigt by a number)

operated in such a way that there is a constant throughput. Alternatively, to mix and dispense the blood and dispense

109822/1752

any suitable, constant throughput thinning agent Structure to be provided.

The line 32 is connected to a microcapillary passage 33 with a reduced diameter, which is shown in FIG has a flat rectangular cross-section. The size of the passage 33 must be made sufficiently small so that the particles go through the same substantially one at a time. If the particles consist of the elements of the whole blood, then there is one Size of about 8 χ 10 / u appropriate. The one in Figures 1 and 2 The appropriately sized microcapillary passage 33 shown may consist of two optically transparent plates 330 and 332 (e.g. Glass) are produced, between which a layer 334 is placed is. This can be deposited from the vacuum and treated with a suitable mask in order to prevent a middle stripe from it deposited on the glass plate. When panels 330 and 332 are put together, the uncoated one forms Median strip the microcapillary passage 33 It should be mentioned that any other suitable technique can be used to lead to the microcapillary passageway of the desired dimension reach. The line 32 is by means of a resilient plug 338 or the like. Attached to the funnel-shaped mouthpiece 336 of the glass layer plate.

Adjacent to the microcapillary passage 33 is for magnification and observation of the particles flowing through the same, a phase-optical system or a diffraction system is provided, that is a source of exposure 34, an aperture 36 with a central opening 38, converging lenses 40, objective lenses 42 and a phase or diffraction plate 44 contains. The optical system forms the sample passing through the microcapillary passage 33 an image plane 46 on which a suitable photosensitive device 48 is arranged. The photosensitive device 48 is enlarged for the sake of clarity.

109822/1752

posed. You can z. B. an npn silicon planar photodetector contain. The size of the photosensitive device or the

Detector 48 is white compared to the size of the sample being imaged

for example a / blood cell, sized so that only a thin Cross-sectional slice or a thin cross-sectional strip of the cell image passes over the detector when the cell passes through the microcapillary passage 33 passes therethrough. This image is designated by 33i in FIG. 3. The signal from detector 48 is over a line 49 led to a signal amplifier A, from which it is appropriately amplified. The signal from signal amplifier A arrives on a line 49 '.

As shown in Fig. 3, a second photodetector 50 is arranged adjacent to the detector 48, which reacts to the light; speaks, that falls outside the projected image 33i. The photo detector 50 is used to compensate for changes in light intensity Light source 34. The reference exposure signal is provided over a line 51 given to signal amplifier A.

The signal from detector 48 becomes one via line 49 * Signal analyzer 52 out. As shown in Fig. 4, contains the signal analyzer 52 has several - narrow band filters 520, 522 and 524, which supply various signals to a plurality of detectors or low-pass filters 526, 528 and 530 via lines 532, 534 and 536. The detectors 526, 528 and 530 give over lines 544, 546 and 548 send signals to circuits 538, 540 and 542, respectively. The circuits 538 and 540 are threshold value circuits that contain Schmitt triggers, for example. On the other hand, the circuit exists 540 from a variable threshold value circuit which, for example, can contain a conventional electronic comparator. The output of detector 526 is branched off also fed into comparator 540 from line 544.

As can also be seen from FIG. 1, the output signals from the circuits 538, 540 and 542 are supplied via lines 56, 58 and 60, respectively

109822/1762

fed into a logic circuit 54. As will be explained in more detail below, the logic circuit 54 can comprise a three-bit binary logic circuit which emits up to 8 different output signals with three inputs. The output signals from the circuit 54 are transmitted via lines 64, 66, 68, 70, 72, 74 and 76 are fed to a counter 62. To the lines 64, 66 _t 68, 70, 72 and 74 are branch lines 80, 82, 84, 86, connected 88 and 90, which lead to a sorting device 78 for Steurung thereof. The signals from the counter 62 can be routed via lines 92, 94, 96, 98, 100, 102 and 104 to suitable display and / or recording devices.

The sorting device 78 is in a suitable manner on one another laminated glass plates 330 and 332 are fixedly attached so that, as shown in Fig. 7, the capillary passage 33 with the interior the same is in connection. As shown in Figures 6 and 7, are on the lower outer surface of the housing the sorting device around a central collecting container 792 several circularly arranged sample collecting containers 780, 782, 784, 786, 788 and 790 attached. Multiple drives 794, 796, 798, 800, 802 and 804 are one end on Fixed inside the housing of the sorting device 78, and at its other end to a plurality of flexible collecting pipes 8o6, 808, 810, 812, 814 and 816, which are arranged in a circle at one end around the longitudinal axis of the capillary passage 33. The pipes go through openings in the base of the sorting device 78 through, the lower end of each tube with the interior of the corresponding collecting container 780, 782, 784, 786, 788 or 790 is in connection. A central tube 818, the upper end of which is flared, lies coaxial with the capillary passage 33 and is in communication with the central collecting container 792 (FIG. 7). The signals from the logic hold 94 are via the Lines 80, 82, 84, 86, 88 and 90 lead to the drive devices 794, 796, 798, 800, 802 and 804 for actuating the same.

109822/1752

The drive devices 794, 796, 798, 800, 802 and 804 can from piezoelectric, electrestrictive or magnetostrictive There are facilities that stretch out when a signal is applied.

To maintain a flow of inert gas through the headers A circulation pump 820 is provided for the collecting tanks. This is done between each collecting tank and the pump inlet multiple inlets are provided, only one of which is shown.

When using the counting device described above, Identifying and sorting the formed elements of the blood is carried out in the container 10 by means of the magnetic stirrer 12 or another suitable ßührers the blood sample with the diluent mixed. In order to prevent coagulation, the mixture is preferably treated with an anticoagulant and kept at a constant temperature by means of a device not shown. The cells are exposed to the diluent separated so that they pass through the device one at a time. Since the response time of the device depends or must be on the distance between the cells when they pass through the Passing capillary passage 33, which in turn depends on the amount of diluent, becomes the proportion of diluent chosen so that the cells will flow within a reasonable response time for the device. For example, at a dilution ratio of 10 ϊ 1 for observation of 1000 Cells per second a cell velocity in the capillary passage of 0.024 m / sec required.

If the cells are observed under normal incoherent light, their microstructure cannot be recognized. This is because the difference in optical path length between the microstructure and the surrounding regions of the cell is very low and there are practically no color or contrast differences. There is only one phase difference that occurs with normal exposure

109822/1752

is not visible. With the phase exposure according to the invention However, the practically invisible grain or microstructure of the cells in the image plane 46 becomes visible when the cells are placed one behind the other pass through the capillary passage 33.

The opening 38 in the diaphragm 36 practically forms a point Monochromatic light source, the light of which hits the microstructure of the cell and the surrounding medium in between falls. Since the refraction values of the microstructures from the surrounding medium result in different optical path lengths the radiation passing through it compared to the rest of the radiation postponed in phase. In other words, through the microstructures the part of the radiation falling on it is bent or deflected, while the rest of the beam is not deflected or is flexed. The deflected beam is through in FIG the dashed lines d shown the undeflected beam by the solid lines 7 · Da is the path length difference between the microstructures and the environment is very small, the phase shift due to the microstructures is equal to one Quarter of a wavelength. The diffraction or phase plate 44 results in a further shift by a quarter wavelength between the deflected and undeflected beam. In this way it results when the rays d and u are in the image plane 46 interfere, a difference in contrast between the microstructure and the environment that is visible and measurable. To the a more detailed explanation of the appearance of the phase exposure refer to Benett, Jupnik, Osterberg and Richards "Phase Microscopy Principles and Applications", John Wiley & Sons Inc., 1951. The Ke.-Dill passage 33 preferably has a flat one rectangular cross-section (as shown) to avoid the need for special corrections, which is the case with circular cross-section would be required.

109822/1752

The image of the through the passage 33, which a part of the transilluminated Observation chamber forms, cell passing through is often, for example a thousand times, enlarged and projected onto the surface of the detector 48. In Fig. 3 is for better clarity half the size of the photodetector 48 is shown greatly enlarged compared to the image 33i of the capillary passage. In fact, the sensitive area of the detector is very small compared to the size of the projected image of the cell, for example on the order of 0.10 χ 0.10 / u. In this way, the individual components of the cell microstructure a continuously changing value of the light intensity falling on the detector 48 is generated when the cell moves over the sensitive Area of the same moves.

Due to the changes in the intensity of the falling on the detector 48 Radiation is changed depending on the choice of the type of detector, the resistance or another suitable size of the same, which leads to voltage changes in the output line 49 leads. This voltage is, if necessary with appropriate modulation by the reference detector 50 via the line 51, amplified in the amplifier A and as an input signal via line 49 'to the signal analyzer. Part of every enlarged cell image that wide is like the detector, only swipes once over the detector. Only those in a plane perpendicular to the optical axis at the focal point lying microstructure is measured. As will be explained in more detail below, however, this is sufficient Information contained in part of the cell image after proper analysis in order to identify and differentiate the cell type.

It has been found that a Fourier or spectral analysis the raw signals through the detector have a special power spectrum results for each cell type. This is true regardless of cell size - maturity and orientation. In other words, one Analysis of a large number of cells of the same type reveals

109822/1752

Essentially identical performance ranges.

The data represented by the curves in Fig. 5 are exemplary for the spectrum of powers of the five types of white cells as determined by Fourier analysis a large number of raw signals for each cell type. The curves in Figure 5 are plotted as relative spectral power levels expressed in terms of frequency, in cycles per unit length. It should be noted that other signal analysis methods too Lead curves which differ from those shown in FIG. 5. However, these curves would also be different for each type of cell.

After determining these individual, different power spectra, it is relatively easy to work within a certain frequency band to choose such relative power spectrum values that distinguish one cell type from the other. As there are many there are distinctive relative power level / frequency band values, as well as many different combinations thereof, that are shown in of a particular construction can be realized separately or together, the examples given below are only intended as a To take an example of a group of values with which to work satisfactorily ksnn. Others might as well Values can be selected with an equally satisfactory working method.

The amplifier is used to identify the white cells A output and via line 49 'to the input of the signal analyzer guided signals are examined by this with regard to the following distinguishing features:

(1) Is the relative power in one cycle per unit length greater than 100?

(2) Is the relative performance for six cycles per unit length greater than or equal to the performance for one cycle per unit length?

(5) Is the relative performance at 10 cycles per retrieval length less than 10?

109822/1752

The following results from a consideration of FIG. 5: By an affirmative answer to question (1) and negative answers of questions (2) and (3) a neutrophil is identified; answering all three questions negatively results in a Monocyte identified; by answering the negative Questions (1) and (3) and an affirmative answer to question (2), a lymphocyte is identified; by an affirmative answer to questions (1) and (3) and a negative answer to question (2), an eosinophil is identified; by a negative Answers to questions (1) and (2) and an affirmative answer to question (3) identify a basophil.

Because of the high hemoglobin content of the red cells and because the red cells, unlike the white cells, have no nuclei or contain grains, their performance spectrum is completely different from that of the "white cells. This is indeed in FIG. 5 not shown, but it has been found that the relative performance of the red cells at 1, 6 and 10 cycles per Unit length is over 100. Therefore, an affirmative answer to questions (1) and (2) and a negative answer identified a red cell in response to question (3). The platelets that make up the last element can be identified when a signal is generated that is not one of the values given above falls.

According to the method of identification given above, the narrow band filters 520, 522 and 524 allow such signals the detectors 526, 528 and 530 through, which in a known manner remove or cut off the signal transitions around the three Frequencies in the ratio of 1, 6 and 10 are centered. Threshold circuit 538 only then generates a signal on the Line 56 when the power of the signal on line 544 greater 1st than a predetermined value (in the given example greater than 100). Thus, a signal on line 56 is equivalent

109822/1752

valent to an affirmative answer to question (1). The electronic Comparator 540 compares the power of the signal from the detector 528 (in the given example with 6 cycles per unit length) with that of the detector 526 (in the given example with one cycle per unit length). It generates on line 58 only then a signal when the power on line 526 is greater than or equal to that on line 544. This corresponds to a affirmative answer to question (2). The threshold value circuit 542 generates a signal on the line 60 only when the power or the corresponding voltage of the signal on line 548 is less than a predetermined value (given Example less than 10). Thus, a signal on line 60 is equivalent to an affirmative answer to the question (3). A signal or a non-existent signal on lines 56, 58 and 60 in predetermined combinations so the. five types of white cells and red cells are displayed. Signals not falling into these combinations, the are eliminated indicate the presence of platelets.

The signals from lines 56, 58 and 60 are fed into the logic circuit 54, which in a typical example is a Can contain a three-bit binary decoder that generates up to 8 output or decision signals on the three input signals, from only 7 of which are used to indicate the identity of each of the five white cells, red cells and platelets. So can a signal on output line 64 indicates a neutrophil, a signal on line 66 a monocyte, a signal on the Line 68 a lymphocyte, a signal on line 70 an eosinophil, a signal on line 72 a basophil, a signal a platelet on line 74 and a signal on line 76 a red cell. These signals become a conventional one Counter 62 or the like. Led, which stores the number of identified cells in a reasonable time when the images the same pass the detector. The signals on the lines

109822/1752

92, 94, 96, 98, 100, 102 and 104 can be displayed in suitable and / or recording devices which the following Display or print data on:

(1) Number of red cells per mm of whole blood.

(2) Number of platelets per nmr of whole blood.

(3) Number of white cells per mm ⁵ of whole blood. (4). Number of any type of white cells.

(5) Total proportion of each type of white cells.

According to Figures 1, 6 and 7, the output signals from the Logic circuit 54 indicating the type of cell as control signals used via lines 80, 82, 84, 86, 88 and 90 for Sorting device 78 are fed. A signal on one of these lines activates the corresponding drive device 794, 796, 798, 800, 802 or 804, so that it extends uiid one of the tubes 8o6, 808, 810, arranged on a circle 812, 814 or 8i6 directly under the exit of the capillary passage, This 33 is moved to accommodate the particular cell type associated with the control signal. As in Fig. 7 by the dashed Lines shown here has the tube 816, driven by the drive device 804 is moved to a position directly below the capillary passage 33. The specific cell type samples will be guided via the pipes into the collecting tanks 780, 782, 784, 786, 788 and 790. The pump 820 forcibly holds a current an inert gas such as nitrogen from the mouth of each tube to its associated sump. on in this way, the cells introduced into the collecting tubes from the capillary passage are drawn into the collecting containers or sucked. If there is no signal to actuate one of the drive devices, the outflow is from the capillary passage 33 is introduced into the central tube 818, which leads to the central collecting container 792, which can accommodate the red cells serve as their share is greatest. Therefore, the line 76 from the logic circuit 54 that the presence of the

109822/1752

red cells, no control connection to the sorting device to have. Collects in the absence of a control signal So the sorting device is the red blood cells.

The white cells are generally larger than the size of the capillary passage 33, so that the white cells are somewhat stretched when passing through it. This is why the detector "sees" 48 always the image of a part of the white cells, which, as explained above, is sufficient for identification. But what about the red ones As regards cells and platelets, it is possible that a small number of them will not be detected by the detector. the Platelets that are smaller than the capillary opening can flow outside the area of the detector. The very thin red ones Cells can bypass the detector if they flow sideways or upright against the walls of the capillary passage.

To ensure that all cells, especially all red cells and platelets, are counted, the pig. 1 can be modified according to Figures 8 and 9, in which similar parts are provided with the same reference symbols. A second detector 110, which may consist of a stripe photosensor, is positioned so that it spans the entire capillary passage and is upstream of detector 48 (see FIG. 9) the upright red cells also observed. The sensitive area of the strip sensor can be very narrow, for example 0.5 x 10 αχ. The signal from the stripe photosensor 110 is fed via the line 111 to the amplifier A ', amplified in a suitable manner and fed to a detector 112 via the line 111'. The amplifier A 'can be modulated by the reference exposure detector signal via the line 51 as in the previous embodiment.

109822/1752

- ₁₉ - 2Q56291

The detector 112 may typically include an electronic integrator with threshold circuits that directly classify the red cells and platelets on the basis of their particular distinct characteristics with respect to one another and with respect to the white cells. Corresponding to the small diameter of 2λχ , a signal in the form of a sharp point is generated by the platelet. The signal from the larger red cells lasts a little longer, so a larger voltage change is produced. The detector 112 can expediently have two threshold values, one for the platelets and one for the red cells. If neither a platelet nor a red cell is observed, a conventional gate 116 is activated via a line 114, which allows the amplified output signal of the detector 48 to be fed into the signal analyzer 52 '. The signals for the platelets and the red cells are fed via lines 120 and 122, respectively, to a counter 124 for the red cells and the platelets, which can be separated from the counter 62 for the white cells. The platelet signal on line 122 is routed via line 126 to sorter 78 so that, as in the previous embodiment, the collection container for the platelet samples can be controlled.

109822/1752

Claims (24)

PATENT CLAIMS (1. ^ Device for the identification of certain microstructure particles of a multiplicity of microstructure particles contained in a fluid, characterized by a conduit device (33) containing a sample, through a scanning or examination device (34, 36, 38, 40, 42, 44) for scanning the microstructure of individual particles in the fluid when the fluid flows through a limited area, by a measuring device (48) responsive to the scanning device through which an electrical output signal is generated, and by means (52, 54) for Analysis and processing of the output signal, by means of which several output signals are generated, each of which is a specific one Particle constituent correspond to the sample. 2. Device according to claim 1, characterized in that that the line device (33) has at least one area which is transparent to electromagnetic radiation and that the scanning device has an exposure source (34) for exposing the area of the line device and of the sample contained therein, and also a phase shifter device (44) to shift the path length of the electromagnetic particles passing through the microstructure components of the particles Radiation versus the electromagnetic radiation passing between them, wherein the measuring device (48) for generating the electrical output signal to the through the area of the line device traversing radiation responds. 3. Device according to claim 2, characterized in that that the exposure source (34) with optical devices (40, 42) for intensifying the image of the sample fluid and the particle cooperates before it strikes the measuring device. 109822/1752 4. Apparatus according to claim 3, characterized in that that the line device (33) is dimensioned in relation to the size of the particles so that the particles substantially are distributed one after the other in the line facility. 5. Apparatus according to claim 3 or 4, characterized in that the radiation-sensitive surface of the The measuring device is much smaller than that which hits it Particle image, so that only a narrow cross-sectional strip of the particle image sweeps over the sensitive surface when the particle moves relative to the scanning device. 6. Device according to one of claims 2 to 5, characterized in that the phase shifter device shifts the path length essentially by a quarter of the wavelength. 7. Device according to one of claims 2 to 6, characterized in that the exposure source is a Contains source of substantially monochromatic radiation. 8. Device according to one of the preceding claims, g e marked by a counting device (62) which is based on the output from the analyzing and processing device Output signals. 9. Device according to one of claims 3 to 8, characterized by a second, adjacent to the first Measuring device (48) arranged second measuring device (110), the radiation-sensitive surface of which is dimensioned so that it the image of the sample fluid spans in a plane which is essentially perpendicular to the longitudinal axis of the conduit device (33). 109822/1752 10. The device according to claim 9, characterized in that that the second measuring device (110) with respect to the direction of movement of the sample fluid upstream of the first Measuring device (48) is arranged. 11. The device according to claim 9 or 10, characterized by a threshold device (112) which is set to predetermined Output signals from the second measuring device responds to the output of the same indicative output signals. 12. The device according to claim 11, characterized by one on the predetermined output signals from the counting device (124) responding to the last threshold value device. 13. The apparatus of claim 11 or 12, marked net by a control device (116) for supplying the output signal the first measuring device (48) to the analyzing and processing device corresponding to one of the second Measuring device derived output signal, which differs from the output signal, so that the predetermined Output signals result. 14. Device according to one of the preceding claims, characterized by at least two collecting devices (810, 816), which are brought into connection with the same downstream of the region of the conduit device can, and by a control device (79 ^ t 804), those of the analyzer and processing facility responds output control signals, so that predetermined individual collecting devices with the line device be associated. 109822/1752 2Q56291 15 <Device according to claim 14, characterized in that net that the number of Samrael establishments of the number corresponds to different particle constituents in the sample fluid. 16. The apparatus of claim 14 or 15> characterized in that the collecting device has a plurality of movable ones Contains tubes (806, 808, 810, 812, 814, 816) each are arranged laterally and in the longitudinal direction at a distance from one end of the line device, wherein the control device Includes drive means (794, 796, 798, 800, 802, 804) for moving the tubes so that they are with the Line device be aligned axia.1. 17 · Device according to claim 16, characterized in that that the drive devices extend to the control signals. 18. Device according to one of the preceding claims, characterized in that the analyzing and processing device for the output signals of the measuring device several narrow band filters (520, 522, 52) and a binary logic circuit (54) contains. 19. The device according to claim 18, characterized in that that the analyzer and processing device includes a plurality of threshold circuits (538, 542) which on the output signals from the narrowband filters respond, wherein the binary logic circuit is responsive to the output signals of the threshold circuits. 20. The device according to claim 19 »characterized in that that the narrow band filters respond to frequencies contained in the output signal from the first measuring device are, essentially in the ratio of 1, 6 and 10, the binary logic circuit consisting of a three-Blt circuit consists. 109822/1752 21. Device according to one of the preceding claims, characterized in that the sample fluid contains blood, and that the particles comprise the shaped elements thereof. 22. Apparatus according to claim 21 and 11, characterized in that the predetermined output signals show the red blood cells or platelets in the blood. 23. Device according to one of claims 16 to 21, characterized characterized in that the axes of the tubes are arranged in a circle around the axis of the conduit means (33) are, and that a central stationary pipe (8i8) is provided is that is axially aligned with the conduit means. ■ 24. The device according to claim 23, characterized in that the drive devices are piezoelectric crystals contain. 109822/1752