FI63491B - PHOTOMETRIC APPARATUS FOER JAEMFOERANDE AV EFFEKTEN AV ETT FLERTAL OLIKA AEMNEN PAO ETT VAETSKESYSTEM - Google Patents

Description

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Patwit · och rAfisCAntyralMIt AnvöJuui uclagd och utUkrtfun puMicurad · 0: 5 (32) (33) (31) Requested ecuotkeu * —Begird prior * · * l8.08.72 USA (US) 2819½ (71) Warner-Lambert Company, 201 Tabor Road , Morris Plains, New Jersey O7950, USA (72) Julius Praglin, East Lyme, Connecticut, David Kenneth Longhenry,

East Lyme, Connecticut, Alan Clarkson Curtiss, Old Lyme, Connecticut,

James Edward McKie, Jr., Ledyard, Connecticut, USA (7 ^) Qy Roister Ab (5 * 0 Photometric device for comparing the effect of several different substances on the fluid system - Photometric apparatus for the effects of various substances on the fluid system vätskesystem (62) Divided by application 2537/73 (patent 53591) -Avdelad frän trap 2537/73 (patent 53591)

The invention relates to improvements in a photometric device.

It has been a problem for the hospital's clinical laboratories to determine the antibiotic to which the disease-causing bacterium isolated from the patient is most sensitive. In the Kirby-Bauer method described in the article entitled "Disc Susceptibility Testing" in "Hospital Practice", February 1970, vol. 5, No. 2, pages 91-100, a barrier zone is measured around an antibiotic plate or vortex in a gel containing bacteria. This takes about one day and requires quite a bit of handling, labor, and exposure to the disease-causing bacterium. A highly automated particle counting system is described in "Applied Microbiology", December 1971, pages 980-986. It gives results in a few hours, but is extremely complex and expensive and kills bacteria, thus preventing replication. Light scattering laser beam photometers have also been used to study changes in the scattering curve obtained with a rotating sensor to determine the bacterial susceptibility of various antibiotics 2 63491. Such systems are based on changes in cell size and shape rather than growth inhibition (from which valid conclusions can be drawn about bacterial susceptibility), require very skill-intensive analysis, and are relatively expensive. It is an object of the present invention to provide a relatively simple and inexpensive photometric device which is very useful in determining the relative efficacy of several different antibiotics in inhibiting bacterial growth by the method described in application 2537/73.

According to the present invention, there is provided a photometric device for comparing the effect of several different substances on a liquid system by determining the light scattering property of several different liquid samples when each sample is in contact with one of said substances. for a given stop phase in the path of the light beam reflected from the light source adjacent to the carriage, each sample causing the light beam to dissipate, to further indicate the scattered light as a light detector located next to the carriage as a time detector it is known that light-transmitting containers for liquid samples are inside the chambers that the cuvette has a support with which the cuvette is releasably attached to the moving carriage, that the attached cuvette is movable relative to the light source and the light detector solely by an index mechanism and is thus immobile for each known stop, during which the sample is in the path of the light beam, that the light detector is positioned relative to the light source and the cuvette travels so as to detect only forward scattered light leaving the sample at a predetermined sharp angle to the axis of the light beam; is an analog signal representing the total intensity of the scattered light detected.

Other features of the present invention will be apparent from the appended claims 2 to 5.

The invention will now be described, by way of example, with reference to the accompanying drawings, in which: Figure 1 is a partially schematic view of a photometric device, i.e. an analyzer and other operational devices; Figure 2 is a top view of the cuvette shown in Figure 1; Fig. 2 is a rear view of the cuvette shown in Figs. 3 and 4, Fig. 6 is a left end view of the cuvette shown in Figs. 2 and 3, Fig. 7 is a right end view of the cuvette shown in Figs. 2 and 3, Fig. 3 is a sectional view of Fig. 3 8-8, Figs. 9-13 are partially schematic views of successive lies when filling the cuvette of Figs. 2-8 from the feed tube, Fig. 14 is a sectional view taken along line 14-14 of Fig. 8; 13 photometric devices or analyzers Fig. 17 is a vertical sectional view taken along line 17-17 of Fig. 13 showing the feed tube placed in a preliminary minimum bacterial nesting test, Fig. 18 is a vertical sectional view of Fig. Fig. 21 is a block diagram of the main control unit shown in Fig. 20, Fig. 22 is a block diagram of the analog-to-digital converter shown in Fig. 20, Fig. 23 is a block diagram of the arithmetic logic unit shown in Fig. 20; of the distribution control card, Fig. 23 is a block diagram of the distribution delivery card shown in Fig. 20, Fig. 26 is a diagram of an exemplary program for the non-volatile memory block shown in Fig. 24, and Fig. 27 is a block diagram of the write shown in Fig. 20; · The devices shown in Figure 1, used in conjunction with each other to compare the efficacy of several different antibiotics (e.g., 12) in inhibiting bacterial growth, include a disposable plastic cuvette 12 for sensitivity testing, an antibiotic plate dispenser 14 for inserting plates 16 into cuvette 12, an incubator cure 30 6 3 4 91 and for shaking and an automatic light scattering photometer analyzer 62 for evaluating bacterial growth and writing the results on a pre-written form or tape 22, as will be explained in more detail later.

Prior to the series of experiments described in more detail herein, clinical isolate has been obtained, transferred to a petri dish 20 and incubated overnight. The bacteriologist then picks up several bacterial plaques of similar shape from the plate 20 using loop 24 and suspends them in a vortex motion in the saline solution in the tube 13. Using the standard photometer method, the suspension in the tube is brought to a constant bacterial concentration, which is checked in analyzer 62 by placing the tube in hole 64 in lid 74 (Figure 17) and reading meter 68. Two milliliters of this suspension is added to 16 milliliters of coarse growth medium 78 is screwed onto the plastic cuvette 12 and its contents are transferred by simple hand movements evenly distributed into the thirteen test compartment S of the cuvette. The antibiotic plates 16 are then fed through openings 26 first exposed by removing the closure 34 by means of a dispenser 14. suspended in the growth medium 28 in block 17. Thirteenth tray S is a control or reference tray. The cuvette is then incubated for three hours in an incubator shaker 30 * constructed for thirty cuvettes. After three hours, cuvette 12 is placed in analyzer 62 and the growth in each compartment So is evaluated. By comparing to the control compartment SQ, the inhibitory effect of each antibiotic in the compartments Sj_ ^ g is calculated and written on a tape or card, as described in more detail below.

The fodder-growing medium has a pH of 7 * 0 and has the following composition in grams / liter.

Ingredient Concentration

Peptones "C" 15 »0

Peptone "S" 5.0

Dextrose 5.5

Sodium chloride 4.0

Sodium sulphite 0.2 l-cystine 0.7 The details of the four devices in system 10 are as follows * 5 6 3 4 91 A) Cuvette 12

When it is desired to measure antlmlkroblsten substances, i.e. effect of antibiotics on the growth of microorganisms in the medium, a chamber (cell) is required for the inoculated medium. Measuring growth in medium by light scattering requires a chamber that both transmits the used light and is geometrically compatible with light scattering by the photometer. A suitable and rapid way to consider the effect of many antlmlkroblsten substances on the growth of a given microorganism is to arrange these optical chambers directly in a row in a single unit. Kyvettl 12 also allows for the convenient delivery of an equal volume of inoculated medium to each chamber S. Kyvettl 12 is also well capable of receiving antibiotic-impregnated paper sheets (rolls) in all of its test chambers, but is unable to take such antibiotic sheet into one control chamber. In addition, the cuvette 12 is waterproof, optically polished, optically reproducible, inexpensive, relatively small, stackable, and can be disposable.

Cuvette 12 is shown in Figures 2 to 8. It is an optically clear and inert plastic, such as polystyrene, and is made by the injection molding process into two parts using optically polished steel molds. After injection molding, the two parts are sealed together with either solvent or ultrasonic energy to assemble the cuvette. Ultrasonic sealing is recommended9 because it avoids damage to the optical surface due to excessive solvent. Cuvette 12 has one control chamber SQ in a straight line, i.e. Barja, and twelve antibiotic test chambers. The only other material in addition to the polystyrene used in the cuvette 12 shown is a flexible polymer such as Krayton. Krayton is a trademark of styrene-butadiene polymer and is sold by The Shell Chemical Co. The Krayton seal 52 and the closure 54 are placed in the cuvette 12 before final packaging.

Cuvette 12 comprises six oeaates (1) Inoculum orifice (P) (Figures 2-7)

A threaded opening that receives 18 to 415 of a threaded tube 78 with inoculated medium, i. inoculum. A Krayton seal 52 placed in the bottom of the opening forms a watertight seal between the cuvette and the inoculum tube.

(2) With a divider (R) (Figures 2-7) This receives an inoculated medium from the inoculum tube when the cuvette is manually turned to a certain position.

(5) Interconnected .blocks 15

The block row 15 extends from end to end of the entire length of the cuvette (except for the division R). The blocks 15 are connected to the distribution space R by the main distribution port 51 and the inoculated medium is taken from the distribution space when the cuvette is turned by hand to bring them down and allow equal volumes of liquid to flow through the distribution ports 33, which is aided by air outflow through the air holes 35.

The area of the openings 33 increases away from the distribution space H.

(4) Light distribution blocks 17 (Figures 7 .1a 8)

Thirteen separate light scattering blocks 17 of the chambers So »S1-12 receive an equal volume of inoculated medium from the interconnected distribution blocks 15 when the cuvette is manually rotated 90 ° about its longitudinal axis to lower the blocks 17. After filling with the inoculum, these thirteen chambers S are isolated by partitions 36 from each other. The manifolds 33 and air holes 35 »located in the upper part of the partitions 36 are well above the level of the medium are the only connections between the chambers. The air holes 35 are necessary to cause the liquid to distribute properly into the lowered manifolds 15, as described above.

(5) Anti-sandwich plate cavity holders (Figures 7. 8 .1a 14)

Twelve perforated hollow rods 29 protrude down into twelve test chambers (S ^, Sg - S ^ g). Each hollow pin, also called a plate holder, receives an antimicrobial paper plate (wheel) 16 (6.5 mm in diameter) through twelve plate openings 26 in the upper surface of the cuvette 12. The plate 16 falls into the plate holder 29 and settles on its flap at its base 73 * Two elution openings E are formed in the wall of each plate holder at the plate 16, allowing the antimicrobial agent (antibiotic) to elute into the inoculum surrounding the plate in the light scattering chamber. A Krayton strip 34 »with twelve protrusions 40 (called closure plugs) is set to close the disc openings 26 to seal each disc holder watertight. The strip 34 passes between parallel rails 34a located on either side of the openings 26 in the upper surface of the cuvette 12.

B) Photometric Analyzer 62 (l) Operation

The photometric analyzer 62 has three main functions: (l) conditioning the inoculum to determine when the microbial concentration of the starting saline inoculum is within relatively narrow and well-defined limits (e.g., 1 to 3 x 10 6 cells / milliliter)} (2) to determine the growth level in all light scattering chambers of the incubated cuvette, and (3) calculate and write a reading from each antibiotic-containing scattering chamber that is readily interpreted as antibiotic susceptibility or resistance of the microorganism.

7 63491 (2) Outside

Figure 16 shows a front view of the device 62 with the doors 74 and 75 closed. Mounted on the instrument housing 66 is a control panel 72 with an inoculum container 68 and a printer slot 70. Doors 74 and 75 allow access to cuvette carriage space 46. An opening 64 is provided in the right door 74 to insert the inoculum tube JS as its lower end rests in the recess 76 of the casting 94 right door 74 only · The left door 75 is for maintenance work. On the left side below the door 75 is the main switch 77 of the instrument · The upper part of the instrument and the front plate 62a are made of ABS plastic and the doors 74 »75 as well as the front panel 72 and the frame 62b are made of steel or aluminum.

(3) Inside

Figures 13, 16 and 18 show the apparatus 62 with the cuvette 12 in place. The cuvette drive mechanism 80 conveys the cuvette 12 from right to left past the photometer light source 82 and the optical system 102. This mechanism has a motor 84 which is connected by a rope 86 to parallel carriages 46 on a sliding carriage 46 · Limit switches 83 and 83 start the forward and reverse movement of the motor 84. The optical sensor 90 in the instrument senses the position of the cuvette by reading the index slots 91 in the slide 92 attached to the carriage 46 (Fig. 15).

Fig. 16 shows the device 62 from the front with the cover plates partially cut away. Drive motor 84 is at the bottom right, transformer 67 is at the bottom left. In the center is a casting 94 that supports the drive mechanisms 80. The photometer sensor 96 is located at the bottom of the casting 94 (Figure 18).

Fig. 13 shows printed circuit boards 98 and 99 »holding the back of the device 62. To the left of the cards 98 is a printer 100.

In the center is a light source 82 and an optical system 102. The optical system 102 has a quartz halogen lamp 82 and a simple two-lens collector system 104. The receiver 106 uses a collimator tube 108 set at a 35 ° angle, as shown in Figure 18. The photometer sensor 96 includes a photocell circuit of any type of operation, as shown schematically in Fig. 19 and physically in Fig. 18. Fig. 19 shows a light sensor or photocell 96 connected to a logarithmic preamplifier 97 *

The printed circuit boards (so-called circuit boards) 98 form the control and regulation electronics of this device. The circuit boards 99 form the calculating and calculating part of the device. Cards 98 and 99 are inserted into U-brackets 101 and are connected by standard wires (not shown) and plug connectors 103.

63491 δ C) Electronics

Figure 19 is a block diagram of an electronic system. The essential components are as follows: (1) Power supply

The power supply provides the necessary voltages for the electronics and the light source of the optical system. The control is such that the system is not affected by mains voltage fluctuations from 95 to 140 V. The system can also be operated at 230 V 50 Hz mains voltage, which is common in many countries.

(2) Light sensor and logarithmic amplifier These components measure the light scattering of a bacterial suspension. The analog output of the logarithmic amplifier corresponds to the logarithm of the light sensor current (microamperes) * The circuit is exceptionally stable and does not require precision over the entire life of the instrument.

(5) Analog-to-digital converter

The light scattering signals from the analog amplifier are converted to a binary number by an analog-to-digital (ä / D) converter. The converter uses "dual slope" integration technology for A-D conversion. This technology guarantees high noise immunity and excellent stability.

(4) Ti e tokoneone unit

The digital format of the light scattering signal is now sent to the computer unit. The result is converted from a binary number to a decimal number.

(5) Printer electronics

The result is then sent to the printer electronics, which puts the calculation result in the printer's office.

(6) Cuvette drive electronics This circuit controls a stepper motor 84 »which drives a cuvette carriage 46 · Commands from the main control unit can start, stop or brake the motor 84 · (7) · Main control unit

When the instrument operator issues commands with the switches on the control panel 72, the main control unit does the following:

Driving command »The main control unit finds out if the cuvette 12 is in place and whether the door 74 is closed. If the drive button 81 is then pressed, the unit synchronizes the cuvette progress according to the A / B converter and the printer. When the last tray of the cuvette is read, the main control unit returns the cuvette to the home position and feeds the printer tape 22 through the slot 70.

Standardization »If the conditioning button 79 is pressed, the test tube 13 can be placed in the opening 64 in the right-hand door 74 and the inoculum (inoculum) in it can be conditioned. Pressing any other pushbutton returns the instrument to standby mode.

Reset: Pressing this button 87 aborts the experiment and resets the cuvette 12 to the home position.

Paper: Pressing button 89 controls the feeding of paper 22 from printer 100.

Activity A) Manufacture of standard wear

The standard inoculum is a suspension of pure bacteria in 0.90 wt.% Sodium chloride solution and has 1 to 3 x 10 'viable cells / ml · This standard saline inoculum in an optically acceptable (i.e., pure female-free) 16 x 129 mm round-bottomed flask gives a scattering signal at an angle of 35 between a log S of 2.2 (1x 10 BO1 / ml) and a value of 1.9 (3 x 10 'cells / ml) when placed in the photometer. The photometer standardization meter 68 has a center range (covering 40 # of the entire range of the meter),

Which is the "area of right inoculum". Its extremes correspond to acceptable disintegration limits. The left area of the meter (covering 30 # of the total area of the meter) means "under" and / or "more organisms", while its right area (covering 30 # of the entire area of the meter) means "over" and / or "dilute with saline".

The standard inoculum is prepared by transferring the bacterial colony or colonies from a 16 to 24 hour agar plate to a 16 x 125 m »standard saline inoculum tube 13 containing 6.0 ml of 0.43 μm membrane filtered sterile saline. . A microbiological loop 24 is used for this task and standard flameing methods are used for sterilization.

While the decision on how many bacterial colonies to place in a saline tube to achieve a suitable concentration range is ultimately a matter of practice, Depends heavily on the consistency and size of the colonies, approximate guidelines for colony diameter, and number can be sketched to quickly achieve a constant inoculum.

Once the colonies have been looped into the saline tube 13 (careful rubbing of the loop against the inside of the tube immediately below the concave portion helps the particularly sticky colonies to detach from the loop), the tube 13 is flamed, vortexed, held for 15 seconds, A white, vertical mark at the top of the tube will help position it (the white mark will be aligned with a similar line on the lid of the photometer). Then press the standardization button 79 and check where the pointer of the meter 68 is located. If the pointer is in the range of the constant or right inoculum 10 63491, the saline inoculum is ready to be introduced into the cuvette. If the pointer is in the "below" range, the tube 13 is removed from the photometer and a colony or colonies are added. If the indicator is in the range "over, sterile, filtered 0.90 wt-56 saline is added to the tube gradually until the inoculum is diluted to the constant range.

B) Filling the cuvette with medium wear (Figures 9-13)

After conditioning, 2.0 ml of saline wear is transferred from tube 13 with a sterile pipette to a 20 x 123 m® tube 78 (flat bottom, silicate, 1Θ to 143 screw cap) containing 18.0 ml of sterile 0.43 μm membrane filtered lush growth medium (as described above). ). The mouth of the tube is flamed by the usual microbiological method, and after the introduction of ino-wear, the tube 78 containing the inoculated medium is closed with its lid. This tube is then gently inverted several times, the lid is removed, and immediately thereafter the tube is screwed upright into the cuvette inoculum tube opening P until it rests firmly on the Krayton seal 32. Figure 9 shows the first step and Figures 10-13 the next steps of filling the cuvette with medium. The cuvette 12 is gently rotated 180 ° from the position of Figure 9 to flow the contents of the inoculum tube 78 into the cuvette distribution space H (Figures 10, 11). The cuvette 12 is placed on its end wall 112 to rest on a horizontal diatomaceous earth 114 · In this position, the longitudinal axis of the cuvette is perpendicular to the horizontal surface, as shown in Fig. 11. Now the cuvette 12 is turned 90 ° so that the medium wear runs from the distribution space R to the interconnected distribution blocks 15, as shown in Fig. 12. This reversal is most easily accomplished by grasping the non-dividing space end of the cuvette 12 and lowering it onto a horizontal surface so that the back side 9 of the cuvette (where the cuvette holder B is located) rests on the horizontal surface 114 * Inoculum runs in 8 seconds. This involves only rotating the cuvette 90 ° about its longitudinal axis to a vertical position (i.e., the position where the cuvette was filled with antibiotic plates), resting on the lower edges 116 of its end walls and the foot 118 below the distribution space R. It is very important that the cuvette remains horizontal during the last turn and this is guaranteed by performing the turn so that both ends of the cuvette remain in contact with the horizontal surface during the turn. A properly filled cuvette should have an equal amount of inoculum in each chamber. The antibiotic plate 16 in each cavity holder 29 must be just and just below the surface of the medium. In some cases, the plates 16 are not on their flaps, but this does not cause problems as long as the plates are in contact with the medium.

6 ό 4 91 C) Incubation of the filled cuvette

As soon as the medium wear is dispensed into a cuvette filled with anti-biotic plates as described above, this is placed in an incubator 50. The workload in a medium-sized clinical microbiological laboratory is likely to be so high that several cuvettes must be placed in an incubator shaker at one time. It is recommended that - if, for example, 10 bacterial isolates are to be tested per hour - 10 standard inoculations are first prepared, after which the cuvettes are filled and placed on one shelf of the incubator shaker 30. They are then simultaneously incubated and mixed for a constant three hours at 36 ° C. During the incubation period, the incubator shaker can be momentarily stopped to insert the second and third cuvette shelves. After a three hour incubation-mixing period, the cuvette shelves are removed and taken to a photometer for reading.

D) Reading the cuvette (l) When the door 74 on the right side of the photometer is opened, the cuvette is placed on its holder B in the carriage 46 of the photometer.

(l) Close door 74 and press travel button Θ1. The carriage 46 passes the cuvette 12 through the photometric analyzer 62, stopping momentarily to read each chamber S.

(3) The 35 ° light scattering from each chamber S ^ _12 is read and is not compared to the light scattering from the first chamber Sq, which has no antibiotic and serves as a growth control chamber. The sequence of events is as follows: (a) The control chamber S is read and the log G31 is calculated: j, o (A). - light scattering of the antibiotic test chamber S after the incubation time t.

- light scattering of the control chamber after incubation time t.

CQ - light scattering of the original standard medium wear (time t - 0).

Initial inoculum concentration8 CQ is an instrumental constant obtained from the known initial inoculum in the first tube *

Q

(b) Log t, the growth index, is now calculated digitally by subtraction

CT

log CQ from log C ^. The result is written on paper tape or a pre-written card.

(c) The log light scattering from the first unknown chamber is now in the reading shift and then calculated, ^ t.

10β (ψ *

Q

The result is divided by log _t and written on a paper tape or pre-recorded card. The process is repeated for each chamber until all 6 o 4 91 12 chambers have been read and the result written.

The net result of the calculation must be proportional to a scale of 0 to 100 to express the inhibitory efficacy of each antibiotic. For example, 0-50 could be a resistance range, a 65-100 sensitivity range, and a 50-65 intermediate range.

(4) Cuvette 12 is returned to the home position and the control panel lights indicate that the test is over.

If insufficient growth has occurred during the 10 hour incubation period (i.e., a growth index of less than 0.9), cuvette 12 can be re-incubated for the same time before final readings are accepted.

The electronics of the analyzer equipment system comprise a data communication line (DATA / BUS) formed by a printed circuit, the so-called a motherboard to which function circuit boards (i.e., circuit boards) are connected, as shown in the block diagram of Fig. 20. Each function card in the system is functionally independent and uses the BATA / BUS system to transfer data and commands between function cards.

The system starts operating from the master control unit (MCU-04011). This function card monitors the power supply controls, the control console, the locking system and the position sensor. When the power is most connected to the system, the main control unit sets the main reset signal to the communication line. All cards connected to this common line monitor this signal and when an instruction enters this line, it resets all deliveries and performs a reset to standby mode. After the power has been maintained for a few seconds, the main control unit monitors the control console and the locking system to start a normal sequence of operations. The locking system requires that the cuvette 12 be in place, the door 74 closed, and the lamp 82 at full intensity. When this state is reached, the main control unit receives commands from the control console 66.

The commands from the control console 66 are transferred to the communication data line (DATA / BUS) and routed via the selection line 1 or 4 to the relevant function unit. Selection line 4 is routed to a write control board (PCC) which controls printer functions via data binary coding lines 9-11. Selection line 1 is routed to an analog-to-digital converter to request the start of a calculation period.

When set to run mode, the main control unit first sends operation messages to the motor 84 »which then causes the cuvette 12 to move past the light beam 120. The position sensor 90 mounted on the cuvette transport mechanism sends notifications back to the main control unit indicating when the cuvette test cell SQ is located in the path of the light beam 120. When this position is reached, the 13 63491 master control unit resets the data link (DATA / BUS) selection line 1 to instruct the A-D converter to receive the analog signal in the logarithmic amplifier of the light sensor. The absolute control of the communication line is in turn transferred to the A-D converter.

The analog-to-digital converter (ABC-04010) responds to the main control unit, requiring a response line RO. The analog-to-digital converter now converts the analog signal received from the logarithmic amplifier to the corresponding binary number.

After doing this, the A / D converter requires the selection line S2 and gives the data lines 0-9 the binary value of the analog signal. Using this selection line, the control of the communication line is now transferred to the arithmetic logic unit.

The arithmetic logic unit (ALU-04012) receives data lines 0 to 9 and responds to the A-D converter, requiring a response line R1. The arithmetic logic unit first determines whether the received data is a control value (i.e., the SQ signal of the first cell of the cuvette 12) or a test value. If the sample received is a control value, the growth index is calculated, -log CQ - log C.J .. If the sample is a test sample, S1-12 is calculated as the inhibition index, 1 ^ -1og (Ax) t - log Ct.

When the calculation is completed, the arithmetic logic unit requires the selection line S3 and transfers the control of the data communication line (DATA / BUS) to the division calculation control card.

The split control card (DOC-O4024) and the split delivery card (DOC-04025) work together to perform a normal split calculation. The distribution control card controls the distribution delivery card in which the actual distribution calculation takes place. After being selected on the selection line S3, the division control card responds on the answer line R2 and takes control of the data link line.

The distribution control card first determines whether the received data is a control sample SQ or a test sample S ^ -12 * When the data represents a growth index, a standard sample, the permanent memory program converts the binary code data into binary code as a decimal representation. When the data is represented by a blocking index, the program performs a calculation I ^ / G ^. Once the relevant calculation has been performed, the distribution control card requires the data line S4 and the data of the data lines 0-9, transferring the control of the data link to the write control card.

The write control card (PCC-04016) receives the data of data lines 0-9 and monitors the binary code on data lines 9 to 11. After being selected on the selection line S4, the write control card responds to the division control card, requiring a response line R3 *

The write control card monitors the operation of the printer when it receives coded pacing pulses from the printer »The data received from the communication line is compared to the printer's scheduling period and the relevant commands are sent to the printer via the printer interface card (PIC-04017).

When the write cycle is completed, the write control card sends a command via the tleto common line to the main control unit to start the motor movement and thus move the cuvette to the next position S. The main control unit causes the cuvette to move and restart the cycle when the cuvette cell is in the light beam path. This process continues until the main control unit receives a lock signal indicating that the cuvette has passed the light station or the cuvette signal has ended. The cessation of the cuvette signal causes the main control unit to normalize the tleto joint line and instruct the printer to drive out the paper, ending the experiment.

The function of the main control pulse (MCU), as shown in the functional block diagram of Fig. 21, is to control and monitor the cuvette with a light beam and to send a counting command when each test cell of the cuvette is in turn in the path of the light beam. To achieve this, the main control unit continuously monitors the operation of the data link (DATA / BUS), the locking system and the control console by means of the signal conditioners of the RC circuit and the position sensor of the cuvette via an active translator signal conditioner. These process operating conditions are monitored by the rocker circuits in the process sequence control section and the AND-NO gate. The status of the process sequence controller is sent via the control stage (Cabledrirer) to the control console, where it is displayed by the solid state indicator, LEDs (light emitting diodes).

The locking detector system requires that the following conditions be met before starting a series of tests.

(1) Cuvette 12 is placed on cuvette holder 44 and. is located on track 120 of the light beam.

(2) Lamp 82 of the optical system illuminates fully.

(3) Door 74 is completely closed to prevent the entry of outside light.

(4) The cuvette 12 is in the starting or rightmost position on the carriage 46. Fulfilling the locking conditions activates the control console and the process sequence controller responds to the press of the drive button 81. Similarly, a two-phase 60 Hz clock is activated and a directional guide is set to indicate the forward movement of the cuvette 12 through the light beam 120.

Pressing the drive button 81 starts the test sequence and the process sequence controller encodes and requires data lines 9 »10 and 11 and selection line S4, which indicates the start of the test sequence. The write control card described later interprets this code. Response line R3 is monitored during this coding to indicate command reception and its effect.

15 6 3 4 91

Requiring a charge line R3 causes the process sequence controller to connect a eunit controller and a two-phase 60Hz clock to allow low-level TTL signals to enter the power controller circuits through the motor control circuits. The power control circuits convert the low level signals into high voltage pulses that drive the stepper motor Θ4 forward.

The cuvette carriage 46 has a slider 92 with index slots 91 · The slider 92 passes through a position sensor 90 which sends a signal back to the process sequence control device to indicate when the cuvette test box is at the light beam. When this signal arrives, the process sequence control device turns off the motor controller, which stops the motor. Single Sequence Delay Element of the Process Sequence Controller Triggered, causing a delay before the next instruction is issued. This delay is sufficient for the cuvette 12 to be able to stop completely and for the photometer 96 to be able to stabilize its analog output. At the end of this delay, the process sequence control device sends a command to the data link (DATA / BUS), reserving the selection line SI, which indicates that the calculation can now be performed. The process sequence control device monitors the return message RO from the return message, which indicates that the calculation has started and that the next logic module has taken over the control of the communication link. When the response line RO is required, the process sequence control device releases the selection line S1 and monitors the busy line. This line indicates that the counting is in progress and that the cuvette 12 must be kept in the path of the light beam 120. The allocation of the response line R3, i.e. the demand, causes the process sequence controller to activate the motor control circuit, whereby the cuvette is transported forward to the next position.

The process sequence controller responds to the pressing of the paper feed switch by encoding data lines 9 »10 and 11 and allocating the data link selection line S4. The write control card (PCC) interprets this encoding.

Pressing the control button on the control console causes the process sequence controller to send a signal to the control console, which activates the photometer output of the meter circuit to display the analog level.

The reset button (key) on the control console normalizes the process sequence controller, which in turn requires a master reset of the communication line. All logic units connected to the communication line monitor this line And normalize to idle when a master reset signal occurs.

The analog-to-digital converter shown in the functional block diagram of Fig. 22 monitors the communication line selection line S1 and begins its process after receiving an instruction from this line. After receiving its conversion command, the analog-to-digital converter responds to the communication line, reserving the response line BO.

The process sequence controller connects the analog source signal via an electronic FET switch to a dual slope integrator circuit. The analog source is connected to the charging circuit of the dual ramp integrator for two time constants to charge the capacitor relative to the voltage level of the analog source. At the end of this time, the process sequence controller switches off the analog source and connects an opposite polarity reference source to the dual ramp integrator to discharge the capacitor. At the same time, the idle clock is switched on to calculate the time required to discharge the capacitor. The threshold detectors detect the time when the capacitor has reached the charge state 0 and "separate" the clock from the time slot counter. The time-slot counter is now a binary number corresponding to the analog signal, and thus a complete analog-to-digital conversion has taken place. The process sequence control device transfers this binary number to the data lines of the communication common line and reserves the selection line S2 by instructing the next logic module to receive the data and act on it. The data is kept on the communication line until the response is sent back to the analog-to-digital converter along the response line H1. After receiving the command from the response line E1, the analog-to-digital converter releases the communication line, transferring its control to the next logic module.

The arithmetic logic gate (ALU) shown in the functional block diagram of Fig. 25 is instructed to start operating using the communication line selection line S2, whereby it responds to this instruction using the response line R1.

The first data sample received by the arithmetic logic unit is stored by the process sequence control device in a 9-bit T-register. The negative value of this binary number is input to the second input of the adder circuit. In this first calculation, the limiter circuit is connected so that a constant, C, e.g. 315 »is fed to the second input of the adder circuit. The resulting decline of 315 - T is called the growth index. A one-time clock gives a delay that is long enough for the adder circuit to settle. At the end of this delay, the calculated amount is connected, i.e. directed, to the data line of the data link and the instruction is given by reserving the selection line S5. The data remains connected until the command of the response line R2 is received ·

The following data samples are stored in the 9-bit S-register from the instruction from the selection line S2. The process sequence controller now switches the interleaver circuit so that the contents of the S register are fed to the adder circuit. The resulting calculation S - T is called the blocking index and is released to the data link as described above.

The functional block diagram of the division control card and the distribution card 63491 17 shown in Figs. 24 and 25 is treated as a single entity because together they perform normal distribution support. Both cards are connected to each other at the back with a ribbon cable. The split control card has a non-volatile memory programmed to perform the split calculation with successive subtraction calculations. Figure 26 shows a program list that is uniquely simple and inexpensive. Following the order of delivery of the program in Fig. 26, a division calculation is performed using a drag representation, which is then subjected to a scale change at the bottom to obtain a response in binary code with a decimal representation. The distribution calculation card has registers and is capable of processing arithmetic data to execute the program.

The first data sample received is a growth index and is processed at addresses 0-3 of the permanent smuist. The following data samples, ie blocking indices, are discussed at addresses 5 - 9 ·

The distribution control card is instructed to operate using selection line S3 and indicates operation using response line H2.

For the growth index, the process sequence controller connects the binary counter memory of the program controller to address 0. The program instruction interpretation circuit (decoder) interprets the code content of the non-volatile memory and sends control commands along the ribbon cable to the distribution card. The growth index is stored in the flip-flops of the B-register.

The contents of the B-register are transferred to the 16-bit A-register via the ϊ-interleaver by adding the +0 from the X-interleaver in the adder circuit. The X-limit is then connected so that the contents of the A register are input to the second input of the adder circuit and the ϊ-limit is connected to input the value -1 to the second input of the adder circuit. The contents of register A are reduced to zero, as indicated by the OVF response at the adder output. In each calculation, an addition is made to the 12-bit BCD input edge coil. (BCD - decimal representation of binary coding). When an OVF response is detected, the process sequence control unit terminates the non-volatile memory program, which connects the program controller to memory location 4 with a pause command. The result register is the BCD equivalent of the B register.

The process sequence control unit connects the result register to the common (ΒΆΤΑ / BUS) data lines and reserves the selection line S4. Upon receiving the command from the answer line R3, the division control card releases the data link.

For the block index, the process sequence controller connects the program controller to the memory address 3 * Ko. the first three steps (steps) of the program tell the data from the common line (DATA / BTJS) with 10000 to obtain the result in the binary code representationf, in which case the data (D) is recycled in a coefficient 6 3 4 91 18 lie through the X interleaver and controlled by the Y interleaver. to perform the following calculation: (D r 410) + (D x 3210) + (D x 6410) - (Dx 1001Q) - A.

The X-limit is then controlled to supply the contents of A to the adder circuit and the Y-limit is controlled to supply -B to the adder circuit. Calculation A to B is performed repeatedly until an OVF response is generated that terminates the calculation, as described above. The result record, which is added with each addition, contains the BCD equivalent of the calculation:

D x 100 B

The zero indicator on the distribution calculation card monitors (monitors) the contents of the B register with respect to the zero value of the digging index to prevent the possibility that the distribution takes place at zero. If zero were detected, the interrupt response signal would cause the process sequence controller to first send a zero value to the next logic module in the normal way along the communication line. The first inhibit index value received by the partition control card causes the process sequence controller to require a master reset line for the communication link and normalize all logic modules and abort the experiment.

The calculation of the normal block index is cut to a scale of 0 to 100. If the value 100 is reached in the calculation in the result register, the limit detector sends an OVF response to the process sequence controller, which then terminates the program in the normal way.

The write control card of Fig. 20, shown in the block diagram of Fig. 27, receives an instruction from the selection line S4 and the codes from the data lines 9 - H · The written control card interprets the data line codes as follows:

DL9 DL10 DL11 CODE COMMAND

001 PAPER FEED 101 TAPE FEED

XIX MARKING PAPER FOR WRITING CHARACTERS

The write control card responds by requesting a response line RO for the first two code instructions and a response line R3 for the latter two code instructions. The data coming from the receivers of the data communication line (DATA / BUS) is stored in the rocker circuits of the register using the selection line S4 and the character character command. The write control board receives the magnetic head time signals from the printer's drum. These pulses are amplified and modified in an operational amplifier and counted in a binary counter. Each invoice code corresponds to a line of characters on the printer drum. The printer sends one reset 19 63491 pulse to the write drum for each revolution. This feedback pulse synchronizes the character set and the process sequence controller. Once synchronized, the process sequence controller opens the gates of the character decoder to begin comparing the character counter and the DF register.

When concurrency occurs, a low-level TTL signal is sent to the appropriate column hammer guide. The hammer controller comprises a transistor capable of activating the hammer solenoid.

Each write instruction is counted in a sample counter, which is similarly compared by a character decoder, and is written along with the sample value. The process sequence controller controls the ribbon and paper feed solenoids. Ko. the Power Transistors in the decoder activate these solenoids.

Claims (5)

20 63491 1. A photometric device for comparing the effect of several different substances on a liquid system by determining the light scattering property of several different liquid samples when each sample is in contact with one of said substances. for the stopping phase from the light source adjacent to the carriage to the path of the reflected light beam, each sample causing the light beam to be scattered, to further indicate the scattered light by a light detector located next to the carriage, the light detector the light-transmitting containers of the liquid samples are the light scattering block inside the chambers (S ^ .-. S ^) and (17), which a the chambers are separated and lined up in a cuvette (12); that the cuvette (12) has a support (B) with which the cuvette is removably attached to the moving carriage (46); that the attached cuvette is movable relative to the light source (82) and the light detector (96) solely by the index mechanism (84, 90, 91) and is thus immobile during each known stop phase period during which the sample is in the path of the light beam (120); that the light detector is positioned relative to the light source and the cuvette travels so as to detect only forward scattered light leaving the sample at a predetermined acute angle to the axis of the light beam, the electrical output signal generated by the light detector responding to the computer is an analog signal; total light intensity. Device according to claim 1, characterized in that the index mechanism (84, 90, 91) comprises a stepper motor (84) under the control of a photoelectric member (90) operatively cooperating with the slots (91) in the part (92) fixed to the moving carriage (46) ) to stop the blocks (17) in the path of each turn of the light beam (120). Device according to Claim 1 or 2, characterized in that the output signal of the light detector (96) is logarithmically amplified by a logarithmic electric current amplifier (97) and converted into binary numerical data in an analog-to-digital converter for use by a data processing device. Device according to claim 3, characterized in that the data processing means comprises a permanent ram for converting the outgoing binary number information into a response in a binary code decimal representation (BCD). 2i 63491 Device according to one of Claims 1 to 4, characterized in that a holding rod (29) placed in each container (S) of the cuvette (12) always keeps one substance in contact with the liquid sample in the block (17). and a port (34) for inserting the substance in the holding stick.