MXPA96002264A - Method and apparatus for aspiring and distributing mues fluids - Google Patents

Abstract

A method and apparatus for aspirating and distributing a sample fluid. The apparatus includes an air source having an outlet orifice coupled with a first orifice of a through-flow pressure transducer. A second orifice of the through-flow pressure transducer is coupled with a first orifice of a sample probe. The through-flow pressure transducer provides signals from the transducer to a detector circuit. In response, to the transducer signals that are provided thereto, the detector detects whether a plurality of different events have occurred or not.

Description

? "METHOD AND APPARATUS FOR ASPIRING AND DISTRIBUTING SAMPLE FLUIDS" FIELD OF THE INVENTION The invention relates to the field of automated fluid sample devices and, more particularly, to an apparatus for detecting when a test probe of an automated fluid sample system is contacted with a liquid.

BACKGROUND OF THE INVENTION As is known in the art, automated analyzers are used in clinical laboratories to measure the various chemical constituents of body fluids, such as whole blood, blood serum, blood plasma, cerebral spinal fluid, or urine and similar ones that are obtained from patients. Automated analyzers reduce the number of trained technicians required to carry out the analyzes in a clinical laboratory, improve the accuracy of the test and reduce the cost per test. 5 Typically, an automated analyzer includes a movable automated fluid system that automatically aspirates a fluid sample from the body of a specimen container of the patient and distribute the sample to a reaction cuvette. The movable fluid system typically includes a pipette that achieves the functions of aspiration and distribution under the control of a robotic arm. The chemical reagents, which are specific for the test that is being carried out, are placed in the cuvette containing the sample, thus mixing the sample with the chemical reagents. Examining the * 10 products of raction resulting from the mixing of the sample and the reagents, the automated analyzer determines the concentration of the specific chemical constituent for which the test is being carried out, in the patient's specimen. Upon completion of the test, the The automated analyzer typically prints the test results, including a sample identifier, a numerical result of the test, and a scale of values ja for the chemical constituent as measured by the test. 20 During an aspiration operation, the robotic arm, under the control of a system controller, places the pipette above a specimen container and moves the pipette towards the container until the pipette comes in contact with the fluid in the container . Then it is done typically operate a syringe-type pump for attract the sample fluid from the specimen container to the pipette. One problem that occurs with moving fluid systems is that occasionally during the aspiration of In a sample, the sample pipette is no longer properly placed in the sample to be aspirated. In this case the air, instead of a specimen of the patient, is attracted to the pipette. This prevents the volume from being sucked. Necessary sample of fluid specimen or to be distributed * 10 completely to the reaction cuvette. If an inappropriate specimen volume of the specimen is mixed with the reagents, an incorrect test result will typically be obtained. In general, when a clinician obtains an unusual test result, the test is repeated and the new result is compared to the previous result. If the two results do not match within a "predetermined" limit, the test must be repeated a second time in order to determine which of the two previous results is valid 20. Therefore, it would be desirable to provide a sample aspiration / distribution device. of automated fluid that detects physical contact between the tip of the probe and a surface of a liquid for this * way to ensure that a fluid has been attracted instead of air to the sample probe.

In accordance with the present invention, an apparatus for aspirating and distributing a sample fluid includes an air source having an outlet orifice coupled with an inlet port of a through-flow pressure transducer. An output of the through-flow pressure transducer is coupled with a sample probe that has a tip that comes into contact with the sample fluid. With this specific arrangement, an apparatus is provided for detecting physical contact between the sample probe and a surface of a liquid sample. The pressure transducer detects pressure changes that result from a number of other events including but not limited to: (a) fluid leaks in a fluid path; (b) aspiration through the sample probe; (c) obstruction of a tip of the sample probe; and (d) fixing and separating a sample tip towards a sample probe. The apparatus may also include a detector circuit coupled with the transducer. In response to each of the previously identified events, the through-flow pressure transducer provides a differential voltage signal to the circuit detector. In a super fi cial sensing operation mode, the air source provides a constant air flow through the pressure transducer and the test, and the probe tip while the test probe is being lowered towards a surface of a fluid. Once the tip of the sample probe comes into contact with the liquid surface, the pressure transducer ^ detects a change in air path pressure ^? 0 where the pressure transducer is located. In response to the change in pressure, the transducer provides transducer signals to the detector circuit. The detector circuit detects the signals provided thereto and provides a control signal to a controller of the system. The detector circuit can be provided with the capability to detect various events including but not limited to: leaks; fluid level; suction integrity; clots; presence of tip and pump servointegrity 20. Each of the events results in the identification of signals that is provided to a system controller for the control of the air pump and the sample probe. Detecting the position of a surface of a fluid, a sample probe moves toward a fluid surface when contact is made, a change in pressure in the air path aligned with the through-flow pressure transducer provides a pressure transducer signal representative of the contact, allowing In addition, the determination and location of the fluid surface. Leaks or leaks in the fluid path of an aspiration and distribution device use the same 1.0 Apparatus driven to occlude the tip of the sample probe by inserting the tip of the sample probe into a sample fluid and detecting the signal provided by the pressure transducer. A detected pressure lower than the normalized pressure indicates that there are leaks in the fluid path of the aspiration and distribution apparatus. If the leak exists, the pressure will not rise to the normal level each time. Normal pressure can be established by placing a calibration tip that does not have an opening for aspiration into the body of the sample probe. The detector circuit also detects when a sample probe tip being coupled with a sample probe in a tip magazine and the removal of the sample probe tip in a tipped position by increasing the pressure when the smaller tip opening is placed above the sample probe. The sensing circuit also detects when a sample probe tip is occluded by an obstruction during an aspiration or distribution operation. The occlusion must be serious enough to activate a predetermined pressure change in the pressure transducer. The detector circuit also provides an indication of whether a system purge valve is closed or open. The sensing circuit also evaluates the servo integrity of the pump by comparing the voltage in the air pump voltage with a pressure transducer voltage in the pipeline and determining if the voltage ratio is within predetermined limits. The detector circuit also determines the integrity of the suction by verifying that an aspiration of air results in a change in pressure within the predetermined limits.

BRIEF DESCRIPTION OF THE DRAWINGS This invention is pointed out with particularity in the appended claims. The aforementioned and other advantages of this invention may be better understood by referring to the following description taken together with the accompanying drawing, in which: Figure 1 is a functional diagram of an automated fluid sample aspiration / distribution apparatus; Figure 2 is a diagrammatic view of an automated fluid sample aspiration / distribution apparatus; Figure 3 is a functional diagram of a detector system; and Figure 4 is a schematic diagram of the 1-0 detector circuits for different functions. Referring now to Figure 1, the aspiration and dispensing apparatus includes a constant air source 12 having an outlet orifice 12a coupled through a bidirectional discharge valve 14 to a first orifice 16a of a pump valve 16 three-way The discharge valve 14 has a vent duct 14 'which is controlled by the discharge valve 14 to open or close as will be described below. The constant air source 12 should be of a type capable of providing a constant air flow at a predetermined rate and pressure to the pump valve 16. This regime and pressure is quite low and depends on the total parameters of the system.

- A second hole 16b of the pump valve 16 engages with a first inlet hole 18a and a gasket 18 at "T" and a third hole 16c of valve 16 is coupled with a ventilation duct. A second hole 18b of the "T" seal canector 18 is coupled with a sample probe diluter 20 that can be provided, for example, as a syringe or a pumped dilution source. ^^ A third hole 18c of the connector 18 of the ™ 10"T" gasket is coupled with a through-flow pressure transducer 22 in a first hole 22a. A second hole 22b of the transducer 22 is coupled with a sample probe 24 which for example can be provided as a pipette holder. In this way, the transducer 22 of The pressure is placed aligned with a fluid conduit between the air source 12 and the sample probe 24. The pressure transducer 22 is preferably placed close to the sample probe 24 to thereby improve the signal to noise ratio of the pressure measurement. The sample probe 24 is controlled by a robotic arm 23 to move to and / or from a trough 31 for aspiration or distribution in an automated test system or to / from the tip stations 25 and test tube 27. In response to the flow of fluid through the pressure transducer 22, the transducer - provides an electrical signal through a signal line 26 to a detector system 28. The detector circuit 28 receives the transducer input signals 22 and provides output signals to the air source 12 and to a microprocessor-based control system 33 through a conduit 30 of the microprocessor. The detector system 28 detects the occurrence or non-occurrence of different events through an analyzer cycle of the automated analyzer system. tf 10 In response to the input signals from the transducer 22, the detector system 28 provides a plurality of functions to be indicated by appropriate output signals when a distal end of the sample probe 24 typically having a pipette tip, is physically contacts a sample 31 of fluid placed in the tube 27 or cuvette 32, towards which the sample probe 24 is lowered by the arm 23. Figure 2 shows in more detail the system of Figure 1. As are shown in it, an apparatus of The aspiration and distribution includes a constant air source which here includes an air pump 70 coupled with an accumulator 72 having a container wherein the air provided from the air pump 70 is stored at a specific pressure such that it remains immediately available to an air supply to a constant low pressure in a hole 72a of the accumulator outlet. In this specific embodiment, the accumulator 72 is provided as a roll of pipe 73 which acts to regulate the pressure and variable flow rates and is decreased in accordance with the slow regulation necessary in the measurement of the pressure. A three-hole connection member 74 positioned between the roll 73 and the air pump 70 has a first hole coupled with the outlet hole of the air pump 70, and a second hole coupled with a first hole of the turn 73. A third hole of the connecting member 74 provides a vent hole to which a ventilation tube 76 is coupled. To ensure proper operation of the suction and distribution apparatus, the air pump 70 provides a relatively low air flow in the outlet orifice 72a of the accumulator 72. To provide this air flow, the connection member 24 discharges a portion of the flow from the air pump 70. The vent tube 70 may preferably be provided as a part of the turn 73 (e.g., which is provided in an internal portion of the coil 73 of the accumulator). Ventilation duct 76 establishes a higher pressure limit to which the pump 70 will be exposed even in the case of complete occlusion of the sample probe. The accumulator 72 may also be implemented using other techniques well known to those skilled in the art. The outlet orifice 72a of the accumulator is coupled through a discharge valve 14 with a common orifice 80a of the pump valve 80 corresponding to the pump valve 16. The pump valve 80 also includes a hole 80b normally open towards the sample probe and a hole 80c normally closed towards the vent conduit 80d. The pump valve 80 is controlled by a controller 94. The orifice 80b of the pump valve 80 engages a first hole 82a of a three-hole connection member 82. A second orifice 82b of the three-hole connecting member 82 is coupled with a diluter 84. The diluent 84 can be provided, for example, as a syringe pump wherein the movement of a piston 86 in a first direction forces the fluid from a housing 88, while the movement of the piston 86 meets in the opposite direction draws the fluid into the housing 88 through the hole 82b. An arrow 90 couples the piston 86 with a linear speed-controlled motor 92. In response to the signals S ^ "received from the controller 94, the stepper motor 92 imposed the piston 86 in a first and second opposite directions within the housing 88. In a preferred embodiment, the controller 94 is provided as a controller based on a microprocessor. A third hole 82c of the three-hole connection member 82 is connected to a tube 96 having an internal diameter that fits into the hole 82c by sealing the connection 10 A pressure transducer 98 has a first orifice 98a coupled with a second end of the tube 96 and a second hole 98b coupled with a first end of a tube 100 typically resilient A second end of the tube 100 is coupled with a first orifice of a probe 102 sample. Therefore, the connecting element 82 and the tubes 96, 100 and the pressure transducer 98 provide a fluid path between the sample probe 102 and the pump valve 80 and the diluter 84. The pressure transducer 98 is provided here as a through-flow pressure transducer of the type manufactured by Micro Switch Division of Honeywell Corporation and identified as a Series 26PC pressure transducer and more particularly, as part number 26PV BFG 6G. The sensitivity of the transducer 98 corresponds to approximately 10 mV / .703 kilogram per square centimeter of pressure difference. Other through-flow pressure transducers having appropriate fluid and electrical characteristics may also be used. To facilitate the connection of the holes 98a, 98b, the transducer with the respective ones of the tubes 96, 100 having essentially different diameters, each of the holes 98a, 98b has coupled thereto a matching tube 101. The matching tubes 101 are provided with a relatively flexible material having a relatively high elasticity characteristic and a non-elongated diameter which is selected to accept the end diameter of the tubes 96, 100 with a slight interference fit. The sample probe 102 includes a probe body having a channel 110 between a first fluid orifice 106a, which is coupled to the line 100 of the system and having a second fluid orifice 106b which engages a tip 108 of the sample probe. In this specific embodiment, tip 108 of the sample probe is provided as a disposable sample tip probe that removably couples to body 106 of the sample probe. It should be appreciated, however, that in some applications it may be desirable to provide the tip of the sample probe as a non-plastic tip. disposable that is permanently secured in the body 106 of the sample probe. The tube 100 that couples the transducer 98 with the sample probe 102 is provided here having a length typically of plus or minus 24.13 centimeters. It is desirable to minimize the distance between the sample probe 102 and the pressure transducer 98. In some applications it may be desirable or even necessary to position the pressure transducer 98 closest to the distance of 24. 13 centimeters from the sample probe 102 and as close as possible to the sample probe 102. In applications where it is desirable to maximize the sensitivity of the apparatus 66 for small changes in pressure, for example, it would be desirable to do directly match the transducer 98 with the sample probe 102. In practical applications, however, it is often not possible due to the size of the circuit components and the packaging space available to achieve this look. Therefore, as a In a compromise, the pressure transducer 98 must be coupled with the sample probe 102 through a tube that minimizes the length of the fluid path between the transducer 98 and the sample probe 102. For this purpose, the pressure transducer 98 can be placed on a printed circuit board (PCB) coupled with the sample probe 102 or as mentioned above, if space permits, the pressure transducer can be placed directly on the sample probe 102. In this specific embodiment, the through-flow pressure transducer 98 has a determined torque in 98c, 98d electric, one of which corresponds to a positive output terminal and one of which corresponds , ^ to a negative output terminal of the transducer 98. The ^ 10 transducer 98 provides a differential output voltage at the output terminals 98c, 98d, representative of the pressure difference between the pressure at the tip of the sample probe and an ambient atmospheric pressure. The transducer 98 is electrically coupled through the lines 111 with a detector circuit 112 in a pair of input terminals 112a, 112b. The detector circuit 112 receives the input signals from the pressure transducer 112 and provides output signals to the controller 94 and the air pump 70 at its output terminals. During operation before aspirating a sample fluid from a tube 27 or cuvette 32, the orifice 80c ventilation valve 80 pump is initially closed and the common holes 80a, 80b and the probe of sample are initially opened. Also, the hole - ventilation of the discharge valve 78 is closed and the piston 86 is positioned so that there is no fluid inside the housing 88. The air pump 70 is then connected by forcing the air through a fluid path leading to the tip 108a of the sample probe. Therefore, air is forced out of the tip of the sample probe at a predetermined rate that creates a predetermined pressure measured by the pressure transducer 98. The sample probe 106 moves to a region where the fluid is expected to come into contact such as in tube 27. When the tip 108a of the sample probe initially contacts the fluid, the tip 108a is occluded by the fluid. This gives The result is that the fluid conduit coupled between the air pump 70 and the sample probe tip 108 is pressed, including the lines 96, 100. The pressure transducer 98 detects the increased pressure level and provides a signal from the transducer to the circuit 112 detector. The detector circuit 112 then provides a control signal to the controller 94 which stops the sample probe from being lowered further or further than a preset point toward the fluid sample. He controller 94 provides control signals to open the -F vent hole of the discharge valve 78 to thereby depressurize the fluid path between the air pump 70 and the sample probe 102 including the fluid path where the pressure transducer 98 is positioned. After the fluid lines have been depressurized, the controller 94 closes the vent of the discharge valve 78. The "Depressurization of the fluid path between the diluter 84 and connecting member 82 before moving piston 86 improves the ability of the system to accurately determine the volumes of fluid to be aspirated and distributed. If the fluid path between the diluter 84 and the connecting member 82 is pressurized When the piston 86 began to move, the diluter 84 would initially be forced to overcome the buildup of pressure in the fluid path. Therefore, instead of sucking the fluid in response to the movement of the piston 86, the pressure in the fluid path between the diluter 84 and the sample probe 102 would equal the pressure in the dilutor, otherwise it is relatively difficult to accurately determine the amount of fluid that was attracted by the diluent 84. However, by opening and then closing the discharge valve 78, the pressure in the fluid line will < % graduates at atmospheric pressure. In this manner, the fluid can be immediately attracted to the tip 108 of the sample probe in response to the operation of the diluter 84. The apparatus also detects leaks or leaks in the fluid paths. To detect leaks, tip 108 of the sample probe is completely occluded and the tubing is pressurized by connecting pump 70. Tip 108 of the probe is occluded and pump 70 is left connected.

-. The pressure in the fluid path between the sample probe 102 and the connection member 82 is therefore allowed to rise to a predetermined limit established during a calibration routine. If there are no leaks, then the pressure will rise to essentially the same calibration level each time the sample probe is occluded. If there is a leak, however, the pressure will not rise to essentially the same level each time. For each system, a calibration routine will be carried out whereby the tip is occluded and the The pressure at which the fluid rises in the fluid paths is determined, of course. The tip 108a can be occluded, for example, by placing a calibration tip on the body 106 of the sample probe. This calibration tip would be provided with an opening in a end of the same to be fixed to the hole 106b of the sample probe and no opening at the second end thereof. The system controller 94 would then perform a sample probe calibration routine to establish a threshold pressure and voltage. Referring now to Figure 3, the detector circuit 112 is shown as including a fluid pressure transducer 122 (corresponding to transducer 98 and 22) having a pair of holes 122a, 122b of fluid and a pair of electrical signal terminals 122c, 122d wherein a differential electrical signal is coupled with an amplification circuit 124. The transducer 122 detects the pressure changes that result in the fluid path due to the occurrence of events specific. For example, transducer 122 detects pressure changes resulting from a number of events including but not limited to some or all of the following: (a) fluid leaks in a fluid path; (b) contact between a tip of the sample probe and a surface of a fluid; (c) air aspiration through a sample probe; (d) obstruction of a tip of the sample probe; and (e) fixing and separating a sample tip to the sample probe. In response to each of these events, the through flow pressure transducer 122 provides a differential voltage signal corresponding to an amplifier circuit 124 at the input terminals 124a, 124b. The amplifier circuit 124 receives the differential signal fed thereto from the pressure transducer 122 and provides a single amplified output signal at the output terminal 124c thereof. The amplified output signal is fed to an input terminal 126a of a signal conditioning and control circuit 126 -F. bomb. A plurality of circuits 128-136 event detectors are coupled with an output terminal 126b of the signal conditioning and pump control circuit 126a to receive a pressure signal and a pump servointegrity circuit 128 is coupled with a terminal 126c from circuit output 126 signal conditioner and pump control. While each of the circuits 128 to 136 will be described below in general, each of the circuits 128-138 receives an input signal from the signal conditioning and signal conditioning circuit 126. pump control at the respective input terminals 128a-136a thereof and compares the signal level of the input signal with one or more of the internally generated signal levels of the signal. Each of the circuits 128-138 can be provided having signal levels different threshold. The circuit 126 can be * «# Implemented with software or otherwise as it is effective. In response to the input signal having a signal level either higher or lower than the threshold signal levels, each of the circuits 128-138 provides representative output signals at the output terminal thereof. Each of the output terminals 128b-138b is coupled with the controller 94 described above in relation to Figure 2. The output signals indicate whether or not a specific event or the current state of the aspiration / distribution apparatus has occurred. It should be noted that each of the circuits 128-138 and 126 can be implemented through a programmed microprocessor or can be implemented alternatively through comparator circuits. An output terminal 126d of the signal conditioner and pump control circuit 126 is coupled to an air pump 140 corresponding to the pump 70. The leak detector circuit 128 receives the signal on line 126b and detects if there are leaks in the fluid trajectories of the apparatus (Figure 2). When a leak detection mode is operated, the controller 94 (Figure 2) presses the fluid paths in the appliance. The leak detector circuit 128 measures the level of V * the signal of the signal on the line 126b and in response to the signal level detector circuit 128 provides a signal to the controller 94. The signal level of the signal of the line 128b indicates to the controller 94 whether or not there is a leak in the fluid paths of the apparatus 66. The fluid level detecting circuit 130 detects when the end 108a distant from the tip 108 of the sample probe is physically contacted and inserted into a sample fluid. The suction integrity detection circuit 132 detects whether or not the pump valve 80 is functioning correctly. After a tip is placed on the sample probe, the orifice 80b of the sample probe of the pump valve 80 (FIG. 2) closes and the air is sucked. This results in a pressure change to a predetermined level. If there is a leak in the pipe or the sample probe orifice 80b did not close, then the pressure change will not reach the appropriate level. Therefore, the detection circuit 132 Intake integrity 20 indicates whether the pump valve 80 has worked properly or not. The clot detector circuit 134 detects whether the sample probe tip 108 was occluded or not during the aspiration and distribution operations. In those applications where probe tip 108 is provided % as a disposable plastic probe tip, the tip detector circuit 136 detects when the tip of the probe is coupled to and decoupled from the body 106 of the sample probe based on a change in pressure to predetermined levels in each case. The pump servointegrity circuit 138 monitors the used voltage signal to the air pump 140 and determines whether or not the appropriate servo voltage is being applied to the pump 140. An incorrect voltage would indicate. 10 an error in the condition such as a blocked flow path. By examining the detector signals that are provided from the 128-138 detector circuits, a number of faults can be detected in the aspiration apparatus and The distribution of Figure 2, for example, a failed pressure transducer, a failed air pump or a discharge valve that has been stuck in the open position (ie, always discharged) can be detected. examining the signals on lines 130b, 136b and 138b. A discharge valve that has been stuck in the closed position (ie, never flushes) can be detected by examining the signal on line 130b. Similarly, the signal 132b can be examined to detect whether the probe orifice sample of the pump valve has been stuck in position open in order to continuously provide air from the air pump 70 (Figure 2) to the sample probe 102. A pump valve stuck in the closed position in such a way that the pump valve stops supplying air to the sample probe 102 can be detected by examining the signals 130b and 138b. An exhaust in the pipeline large enough to affect the distribution operation or the level detector operation can be detected by examining the signals 0 of lines 138b, 132b and 128b. It should be noted that each of the event detector services 128-138 compares the respective input signal fed thereto with the internally generated threshold voltage levels to determine whether specific events have occurred or not. In response to the comparison operations, each of the 128-138 event detector circuits provides an appropriate output signal to the controller 94. Referring now to FIG. 4, the details of the signal conditioning and control circuit 126 are shown. of pump. The input to the signal conditioning and pump control circuit is coupled through a resistor 155 to an inverting input of an amplifier 160 of investment. The reversing amplifier 160 provides the signal of the line 126b to the detectors 128-136. A resistor Rl and a capacitor Cl are coupled in a negative feedback path as shown between the output terminal of the reversing amplifier 160 and the inverting input terminal of the amplifier 160. A non-inverting input of the reversing amplifier 160 is coupling with a first terminal 162a of a sample and retention circuit 162. A load storage capacitor 164 for the holding function is coupled between a second terminal 162b of the sample and hold circuit 162 and the ground. A third terminal 162c of the sample and latch circuit 162 is coupled to an output terminal of a second reversing amplifier 166 and a fourth terminal 162a of the sample and latch circuit 162 is coupled to the controller 94 of the system. The non-reversing input of the second reversing amplifier 166 is coupled to ground and the inverting input of the amplifier 166 is coupled through a resistor R2 to the output terminal of the first reversing amplifier 160. A feedback capacitor C2 is coupled between the output and the inverting input of the amplifier 166.

The output terminal 160c of the first amplifier 160 is also coupled through a resistor R3 with an inversion input of a third reversing amplifier 170. The input of an inversion of the reversing amplifier 170 is coupled with a reference voltage 171 through a voltage divider network 172 having the resistors R4, R5 which are selected together with the voltage level of the reference voltage 171 such that a predetermined threshold voltage is provided to the input terminal 170b of an inversion of the reversing amplifier 170. A capacitor C3 is coupled between the output terminal and the inverting input of the amplifier 170. The output terminal 170c of the third reversing amplifier 170 couples with a first terminal 174a in a sample and hold circuit 174. A load capacitor 176 is connected between a second terminal 174b of the sample and hold circuit 174 and ground. A third terminal 174c of the sample and latch circuit 174 is coupled through a resistor R6 to an input terminal 178c of a voltage regulator circuit 178 and a fourth terminal 174d of the latch sample circuit 174 is coupled to the controller 94. of the system. The system controller provides a control signal to the sample and retention circuit caused that it works in either the sample mode or the hold mode. The voltage regulator 178 has a voltage input terminal 178a coupled with a source 179 of reference voltage. A voltage output terminal 178b of the regulator 178 is coupled through a resistor to the control pump 140. A diode 184 zener is coupled between the input 178c and the earth, ¿í. holding the input so that it does not exceed a predetermined voltage w 10. A resistor 186 is coupled between the node 180 and the anode of the zener diode 184 as shown. A switch 192 is coupled between a second terminal of the pump 140 (corresponding to the air pump 70) and ground. 15 In response to a first control signal from the controller 94, the switch 192 is forced to drive, activating the air pump 140. The sample and hold circuit 162 establishes a reference or normalized voltage level for the signal on the line 126b which corresponds to a reference or normalized pressure level in the pressure transducer 122. The sample and retention circuit 162 is placed in a sample mode by means of the controller 94 where 25 connects a signal path between the output of the amplifier 166 and the non-inverting input of the amplifier 160. The amplifier 166 provides an output signal to the sample input and hold terminal 162c. The amplifier 166 provides a bias signal at its output which is applied to the non-inverting input of the amplifier 160 through the sample and hold circuit 162 until the signal provided at the output of the amplifier 100 is driven to a level of w '10 voltage that corresponds to ground. At this point, the controller 94 provides a second control signal to the sample and hold terminal 162d which places the sample and hold circuit in the hold mode. The voltage level of the sample and retention circuit is therefore both by recording a value that causes the output of line 126 to be zero for any pressure that is detected. Then, the voltage level of the signal in the signal 126b is representative of the relative pressure changes detected by the pressure transducer. 20 System operation: (1) a system cycle begins with the sample probe 102 (Figure 2) without a tip. The controller control signal 94 (Figure 2) polarizes the switch 192 to its non-driving state thus decoupling the ground air pump 140 and thereby disconnecting the air pump 140. With the air pump 140 disconnected, there is no pressure in the fluid path where the through flow pressure transducer 122 5 is placed. Therefore, the pressure transducer 122 provides a differential output signal corresponding to a zero pressure to the input terminals of the amplifier 124 (Figure 3). Likewise, with the ^. pump 140 disconnected, voltage regulator 178 and mv 10 diode 184 zener maintain voltage on line 178b at a graduated voltage level. Also, the output terminal of the amplifier 170 provides a voltage level that corresponds to the rail voltage. (2) The controller 94 then provides a control signal to the sample and hold circuit 162. In response to the control signal, the sample and hold circuit 162 drives the output 126b to zero volts. (3) The controller 94 then provides a control signal 20 for connecting the pump valve 80 (Figure 2) and also provides a second control signal to bias the switch 192 to its driving state thereby connecting the air pump . When the pump is initially connected, the voltage across the pump is a high voltage. When the pump 140 is first connected, ^ Wf the amplifier 170 drives the pump voltage so that the line 126b is at the voltage at its non-reversing input. Before connecting the pump, the output of the amplifier is to the positive rail driving current through the resistor 176 and forcing the line 178c to the zener voltage graduated by the zener diode 184. This causes a rapid rotation of the pump 140. With the passage of time, the amplifier 170 drives the circuit resulting in its output decreasing to As the line 126b increases with the accumulation of the pressure signal from the transducer 122. At a desired pressure voltage, the sample and hold circuit 174 causes by means of the controller 94 to retain that voltage during a cycle. Also, in response to the fact that pump is connected, the pressure in the fluid lines of the system rises rapidly. (4) After a typically 500 millisecond period, the controller 94 provides a control signal on the line 176d to the control hole of the second sample and hold circuit 134 thereby placing the sample and hold circuit in the mode retention. The procedure zeros of the output line 126b of step "2" are repeated here at a very fast recalibration step. < J (5) The controller 94 then measures the output of the integrity circuit 138 to determine if the signal falls within a predetermined voltage range. If the signal has a voltage level outside a scale of predetermined voltage, then an error signal is generated by the controller 94 and stops processing. If the signal has a voltage level within a predetermined voltage scale then the continuous processing and the controller moves the sample probe 102 10 through the robotic arm 23 to a station 25 (Figure 1) where it can pick up a tip of disposable probe. (6) Line 126b again graduates to zero as in step "2" and a new tip is placed on the probe.

During the placement of the probe tip in the body of the probe, the air in the line experiences a brief transient current as the tip is inserted. Controller 94 examines the signal on line 136b of detector 136 to determine whether the signal corresponds to a pre-graduated level during a predetermined period of time to confirm the placement of the tip. The filter of the pump is connected and all the values remain as they have graduated. (7) Controller 94 disconnects pump valve 80. The pump pump 140 remains in operation. -m (8) Line 126b is reset to zero according to step "2". (9) Once the tip has been coupled with the body of the sample probe, the controller 94 engages the stepper motor 92 which draws the piston 86 toward the cylinder 84. Since the tip has not yet been placed in the a fluid, this gives popr result that the air is sucked towards the fluid trajectories through - ?. the disposable sample probe tip. After that complete the aspiration the controller determines if there is an error through the circuit 130 suction integrity detector (Figure 3) as follows: (10) The controller 94 connects the pump valve 80 thereby providing air flow towards the sample probe 102. Controller 94 then zero line 126b. (11) The controller 94 moves the sample probe through the robotic arm 23 to a position where the sample probe can give access to a tube 27 of shows that it retains a fluid sample. (12) The sample probe is lowered in the direction of the fluid tube 27. Once the disposable probe tip comes into contact with the fluid the pressure transducer 122 detects a change in pressure and provides a signal to the detector circuit 112. In response - to the signal provided thereto from the pressure transducer 122, the detector circuit 130 generates a signal at the output 130b and provides the signal to the controller. (13) While line 130b is monitored, controller 94 moves the disposable tip toward the fluid sample to a predetermined penetration depth that is selected to allow aspiration of the necessary fluid. * 10 (14) After the disposable tip moves to a predetermined depth, the controller waits for a predetermined period of time typically of about 500 milliseconds and then examines the signal on line 128b which is provided by the circuit 128 of exhaust detection (Figure 3) to determine if leaks or leaks are present in the system. (15) The controller 94 provides control signals for connecting the discharge valve and disconnecting the air pump as described above in order to to normalize the fluid line in preparation for the suction fluid. (16) The controller 95 then disconnects the pump valve 80, and (17) couples the stepper motor 92 (Figure 3) causing the diluent to draw the fluid Ü to tip 108 of sample probe. The controller 94 also monitors the signal on line 134b that is provided by the clot detector 134 to determine if the fluid path of the sample probe has become clogged during the aspiration operation. (18) If no clot detection occurs, then the controller 94 moves the sample probe to a position at which a sample fluid can be distributed to a cuvette 32. * 10 (19) The controller 94 provides a control signal causing that the stepper motor distributes the sample fluid to the cuvette 32. The controller again examines the signal from line 134b to determine whether the fluid path of the probe has been obstructed during the distribution operation. (20) After the dispensing operation is completed, the controller 94 moves the body of the probe to eject the disposable tip. The signal on the line 136b which is provided by the tip detector circuit 136 (Figure 3) must present a few milliseconds indicating in this manner that the disposable tip was removed from the body of the sample probe). - ^ ß An escape or leak is detected by the leak detection circuit 128 (Figure 3) as follows. As described above in relation to Figure 4, the disposable tip of the sample probe is moved towards the fluid sample with the air pump connected thereby allowing detection of the level of the fluid sample. Once the disposable tip is placed in the fluid, the air pump stays connected allowing in this way the pressure to accumulate in the. 10 fluid lines. The air pump provides the air at a flow rate that does not allow the pressure to rise to a level that causes the formation of a bubble in the sample fluid. Instead of this, the pressure in the sample probe and the fluid path leading thereto accumulates to a static pressure. The pressure scale of the static pressure may be known from a calibration step which will be described below. The default static pressure level corresponds to an equalizing pressure. Ideally, the pressure should accumulate at the same value each time, even when in practice it is recognized that this will not be the case. However, if there is a hole or leak of fluid in the fluid path, then the pressure will not rise to the level predetermined and therefore the signal of the line 126b does not will reach a comparison threshold voltage level set in circuit 128. Circuit 128 therefore provides an output signal on line 128b which indicates that the threshold has not been reached and that there is an escape or leak in the path of fluid. The static pressure and therefore the necessary threshold in circuit 128 will not be the same for each instrument. Instead of this, it is a function of the length of the pipe, the diameters of the pipe and the F 1.0 mechanical tolerances of each of the system components, etc ... Therefore, a calibration step is used to graduate the threshold. To calibrate the system, steps 1 to 5 are repeated as above. The sample probe is completely occlude for example, by placing a calibration tip that has a closed end on the body of the probe. This establishes a calibration voltage for the comparison threshold of circuit 128. The current threshold voltage in circuit 128 is set to a voltage smaller than that to ensure that the voltage on line 126b exceeds the threshold where no leakage is present and output 128b changes to reflect that. The level sense detector circuit 130 responds to the signal of line 126b and compares the same with an internal reference. The output on line 130b is < # Elevated until the disposable tip comes into contact with the sample fluid. Then, with the air pump continuing to provide a resultant airflow in which the pressure transducer 122 causes an elevation of the signal on the line 126b above the threshold voltage, the signal on the line 130b typically decreases to approximately zero volts. , indicating in this way that a physical contact has occurred between the sample probe and the sample fluid. The suction integrity circuit 132 receives the signal on line 126b and if it is less than a set threshold voltage level, it internally provides an output signal on line 132b having a high voltage, typically 5 volts. Once the level of the When the signal on line 126b reaches the threshold voltage, circuit 132b provides on line 182b a low voltage (typically zero). W ^ ~ During a suction operation, the vent hole of the pump valve opens and the orifice of the sample probe of the pump valve should be closed in order to isolate the discharge valve, the coil and the air pump from the diluter and the pressure transducer. However, it is not possible to determine if the pump valve worked correctly. Therefore, with the sample probe orifice of the pump valve «Closed, the air is sucked through the sample probe. This should result in a pressure change in the fluid path where the transducer is placed. If there is an escape in the pump valve, however, the pressure generated due to the suction operation will not rise to the appropriate threshold level for the circuit 132. Consequently, the pressure transducer 122 would provide a signal having an amplitude insufficient to reach the threshold voltage. The circuit 132 therefore provides in the output terminal 132b a signal having a voltage level which indicates that an exhaust was detected in the pump valve during a suction operation. The clot detection circuit 134 has a double comparison function with a pair of graduated threshold levels to detect if the voltage level in the signal of the line 126b decreased within a predetermined voltage range between them. This is due to that the pressure transducer 122 (Figure 3) measures different pressure levels during the suction and distribution operations. For example, when the diluent piston stops after being moved during a suction operation, the pressure measured by the transducer must decrease to less than a predetermined threshold voltage.

* If the pressure transducer fails to indicate this pressure drop, then the voltage level of the line 126b signal would not change indicating therefore that the tip of the sample probe was occluded. Similarly, during a distribution operation the pressure must remain above a predetermined threshold voltage. If the pressure transducer detects a pressure drop or rise during a distribution operation, then the voltage level F 10 of the signal on line 126b would likewise change to a level that falls outside the predetermined threshold voltage scale thus indicating that the tip of the sample probe was occluded during the distribution operation. The clot detection circuit can also be of the type described in the copending patent application serial number filed (CCD-192XX - VOLUME DETECTION APPARATUS AND METHOD) assigned to the concessionaire of the present invention and incorporated herein by reference. The pump integrity servo circuit 138 with input terminal is coupled with an output terminal, line 126c of sample and hold circuit 174 (Figure 4). If the air pump voltage signal is not within the predetermined scale, then the Servocircuit 138 of pump integrity provides a output signal indicating it in the output terminal 138b. This signal is only examined by the controller 94 when the pump voltage is graded. Two threshold voltages are provided in the circuit 138 graduated respectively to opposite voltage ends. The threshold voltage levels are selected in such a way that if the level of the line signal 126c exceeds these threshold levels it indicates that the pump control circuit is unable to servo drive the pump in the manner F 10 desired. Therefore, when the signal of line 126c is between these thresholds, the output voltage level of line 138c is high. When the signal of line 126c is outside the threshold voltage scale, the output signal is approximately zero volts. 15 It should be noted that in some embodiments it may be preferable to detect the level of the signal in the signal of ^ line 126b instead of the signal on line 126c, in which case the threshold voltage levels would be graduated differently. The peak detection circuit 136 has a pair of threshold levels internally graduated at +/- low voltages that define a scale of approximately zero for the signal level of the line 126b above which the signal of the line 126b goes over the installation of the tip and below which the line 126b goes over the removal of the tip. Within this scale, the output 136b is high; outside the scale the output is low. When a disposable sample tip is placed in the body of the sample probe, the voltage level of the signal of line 126b will rise rapidly. The controller 94 examines the signal level of the line 136b at the output terminal of the detection circuit. # 10 tip. The controller 94 detects the signal level of the signal on the line 136b and verifies that the signal remains elevated for a predetermined period of time, typically about 10 milliseconds. Then there is a relatively high probability that a The tip was in the tip holder and a disposable tip was actually placed on the body of the probe. Similarly, when a disposable tip is removed from the body of the probe, a pressure change occurs and is detected by the pressure transducer. He The pressure transducer provides a corresponding output signal having a transient voltage less than that of the scale that is detected. In case a tip is not removed, the controller 94 detects the signal of the line 136b staying within the scale and acts to prevent a new tip from being placed on top of a old tip that had not been removed. Having shown the preferred embodiment, those skilled in the art will understand that many variations are possible that are still within the scope and spirit of the claimed invention. Therefore, the intention is to limit the invention only as indicated by the scope of the claims. #

Claims (23)

1. An apparatus for aspirating and distributing a sample fluid comprising: a constant air source having an outlet orifice; a pump valve having a first orifice coupled with the outlet opening of the air source, A constant, having a test probe orifice and having a vent hole, a connecting member having a first orifice coupled with the sample probe orifice of the pump valve having a second hole and having a third hole; 15 a diluter having an outlet hole coupled with the second orifice of the connecting member; a through-flow pressure transducer having a first hole coupled with the third hole 20 of the connecting element and having a second hole to provide a pressure signal; and a sample probe having a first hole coupled with the second orifice of the through-flow pressure transducer; Y a controller for the air source, the pump valve, the diluters and the sample probe that function as a function of the pressure signal.

2. The apparatus according to claim 1, further comprising a discharge valve having a first orifice coupled with the exit orifice of the constant air source and having a second orifice coupled with the first orifice «I ^ e to pump valve and ventilation duct 10 controlled.

3. The apparatus according to claim 2, further comprising an accumulator having a first hole coupled with the exit orifice of the air pump, an exit orifice coupled with the 15 inlet port of the discharge valve.

4. The apparatus in accordance with the. claim 3, further comprising a connector having a first hole coupled with the outlet opening of the constant air source, a second 20 hole coupled with the inlet hole of the accumulator and the outlet hole coupled with the ventilation tube.

5. The apparatus according to claim 4, wherein the pressure transducer of 25 through flow provides the pressure signal in a pair of electrical output terminals and in response to pressure changes in a fluid path between the sample probe and the connector element, the through-flow pressure transducer provides a 5-output, differential signal at the pair of electrical output terminals .

6. The apparatus according to claim 1, wherein the controller comprises an "H microprocessor.

7. The apparatus according to claim 1, further comprising a detector circuit coupled with the pressure signal from the through-flow pressure transducer to send signals to the controller of a plurality of conditions reflected by the pressure 15 in the transducer 8.

The apparatus according to claim 7, wherein the detector circuit comprises: an amplifier circuit having a first terminal coupled to the through-flow pressure transducer having a second terminal; has a first terminal coupled to the output terminal of the amplifier circuit and having a second terminal 25 coupled with at least one of: (a) a leak detector circuit; (b) a fluid level detector circuit; (c) an aspiration integrity circuit; (d) a clot detection circuit; (e) a tip detecting circuit; and (f) a pump integrity servo circuit; each of which has a nominal status signal graduated therein by the conditioning circuit. of signal level under the operation of the controller.

The apparatus according to claim 8, wherein the signal conditioning circuit comprises: a first reversing amplifier having a negative input terminal coupled to the first terminal of the signal conditioning circuit having an input terminal positive and that has an output terminal; a second reversing amplifier having a negative input terminal coupled to the output terminal of the first reversing amplifier having a positive input terminal coupled to ground and having an output terminal; a sample and hold circuit having an input terminal coupled to the output terminal of the • * second inversion amplifier having an output terminal coupled to the positive input terminal of the first inversion amplifier and having a control terminal; and 5 the controller is coupled with the control terminal of the sample and hold circuit.

10. An apparatus for aspirating and distributing a sample fluid comprising: a constant air source having a ''10 exit hole; a discharge valve having a first orifice coupled with the exit orifice of the constant air source and having a second orifice; a pump valve having a first orifice 15 coupled with the discharge orifice of the discharge valve having a sample probe orifice and having a vent hole; a connecting member having a first orifice coupled with the sample probe orifice of the pump valve, having a second orifice and having a third orifice, a diluent having an outlet orifice coupled with the second orifice of the connection member; a through flow pressure transducer having a first hole coupled with the third hole of the connecting element and having a second hole to provide a pressure signal; a sample probe having a first hole coupled with the second orifice of the through-flow pressure transducer; and a controller for the air source, the discharge valve, the pump valve, the diluter and the probe that function as a function of the pressure signal.

The apparatus according to claim 10, further comprising a detector circuit coupled with the through-flow pressure transducer.

The apparatus according to claim 11, wherein the detector circuit comprises: an amplifier circuit having a first terminal coupled to the through-flow pressure transducer and having a second terminal; a signal conditioning circuit having a first terminal coupled to the output terminal of the amplifier circuit and having a second terminal coupled with at least one of: ^ t (a) a leak detector circuit; (b) a fluid level detector circuit; (c) an aspiration integrity circuit; (d) a clot detection circuit; and (e) a tip detecting circuit; and (f) a pump integrity circuitry each of which has a nominal status signal level graduated therein by the signal conditioning circuit under the operation of the controller.

The apparatus according to claim 12, wherein the signal conditioning circuit comprises: a first inversion amplifier having a 15 negative input terminal coupled with the first terminal of the signal conditioning circuit, having a positive input terminal and having an output terminal; a second investment amplifier that has a The negative input terminal coupled to the output terminal of the first reversing amplifier having a positive input terminal coupled to ground and having an output terminal; a sample and hold circuit having an input terminal coupled to the output terminal of the second inversion amplifier having an output terminal coupled to the positive input terminal of the first inversion amplifier and having a control terminal; and the controller is coupled with the control terminal of the sample and hold circuit.

14. A method to determine if physical contact has occurred between the probe and a surface of a liquid that comprises the steps of: (a) establishing a normalized pressure representing the voltage corresponding to a zero pressure signal in a through-flow pressure transducer; (b) provide a constant air flow through the pressure transducer and a 15 shows; (c) moving the sample probe in a direction of ^ A fluid; (d) detecting a change in pressure in the fluid path aligned with a transducer 20 through flow pressure; and (e) providing a pressure signal from the transducer representing the fluid contact in response to the change in pressure in the fluid path.

15. The method according to claim 14, wherein the step of establishing a normalized pressure voltage comprises the step of: depressurizing a fluid path between an air source and a sample probe wherein the fluid path includes a transducer through flow pressure. providing a first signal having a first voltage level towards a first input terminal in an inversion amplifier coupled with the through-flow pressure transducer; driving an output signal of the inverting amplifier to a reference voltage representative of a pressure level in the through-flow pressure transducer; taking samples in a sample circuit and retaining the predetermined reference voltage at the output terminal of the amplifier; placing the sample and hold circuit in a hold mode to maintain a threshold voltage in a second terminal of the amplifier circuit.

16. A method for detecting leaks in a fluid path of a suction and distribution apparatus that includes the steps of: coupling a constant air source to pressurize a fluid path having an aligned through-flow pressure transducer that is positioned between the constant air source and the 5 shows, occlude the sample probe; and comparing a signal that is provided by the pressure transducer with the occluded probe to a threshold signal l.

17. The method according to claim 16, wherein the step of occluding the sample probe includes the step of inserting the sample probe into the sample fluid.

18. The method according to claim 15. 17, wherein after the step of inserting the sample probe into the sample fluid, the method further comprises the step of comparing a signal provided by ? i ^ the through flow pressure transducer with a threshold signal.

19. A method for verifying the integrity of the suction of a suction and distribution apparatus including the steps of: coupling an aligned through-flow pressure transducer positioned between an air source and a 25 diluter on the one hand, and a sample probe on the other part, when the fluid path is in the suction mode which isolates the air source from the diluter via a valve; compare an output of the pressure transducer during aspiration with a reference to determine the integrity of the valve.

20. A method for detecting that a clot has occurred in a suction and distribution apparatus that includes the steps of: coupling an aligned through-flow pressure transducer placed between a diluter and a sample probe when the fluid path is at each Aspiration and distribution mode; compare an output of the pressure transducer during aspiration and distribution with respective references to determine the integrity of the fluid path.

21. A method for verifying tip placement and removal in a suction and distribution apparatus that includes the steps of: coupling an air source to provide an air flow in a fluid path beyond the pressure transducer aligned through flow placed between the air source and a sample probe, when the probe is receiving and removing a sample tip; compare an output of the pressure transducer during the insertion and removal of the tip against respective reference to determine the integrity of the insertion and removal of the tip, respectively.

22. A method to verify the integrity of the pump of a suction and distribution apparatus that Includes the steps of: coupling an air source with a servo circuit to provide an air flow in a fluid path beyond an aligned through-flow pressure transducer placed between an air source and a diluter on the one hand , and a test probe by another 15 part where the air flow will provide a desired pressure; Y _. compare a servo signal during the coupling * of the air source with the respective references in order to determine if the servo circuit is also capable of 20 Servo drive the air source.

23. The method of confomity with claims 16, 19, 20, 21 or 22, further comprising the step of establishing a normalized pressure and a servo signal respectively for the comparison step.