LEVEL SENSOR AND WASHER UNIT

Abstract: A fluid level sensor and a washer unit are provided for an automated immonoassay processing system. A washer head (13) is vertically movable by a drive (2) above a reaction tray (8) having fluid (15) in separate cells. The level sensor comprises two electrodes arranged along a fluid path within aspirator tips (6). The electrodes are held at different electrical potentials and are effectively insulated from each other. If fluid is aspirated along the fluid path then the electrodes are bridged. Control means (1) is arranged to detect any change in conductance between the electrodes thereby indicating the presence of fluid (15). The vertical height of the washer head is determined relative to the sample thereby enabling the device to determine the level of the fluid (15).

Description: Level sensor and washer unit The present invention relates to a level sensor and a washer unit for an automated immunoassay processing system. When biological, chemical or biochemical products are tested or analysed, these products may be dispensed into cells in reaction trays to enable analysis of the various products to be performed. After a reagent or a plurality of reagents have been dispensed into the cells in the reaction tray, the reagents are then left for a period of time to allow incubation of a biological process or for a chemical reaction or the like to occur. After this period of time it is necessary to remove the reagent from the cells and wash the cells so that further analysis may be performed. The washing of the cells in the reaction tray is conventionally performed by separate means to the means which dispenses reagent. After the incubation period, it is desirable to ascertain whether the correct amount of reagent has actually been dispensed into the cells of the reaction tray,- otherwise the desired process or reaction may not have occurred. Once the reagent level has been checked, the reagent is aspirated from the cell. It may also be desirable to check that all of the reagent has been removed from the cells before commencing a washing cycle. During the washing cycle it is also desirable to be able to detect whether the correct amount of washing or cleaning fluid has been dispensed into the cells of the reaction trays and to determine whether all the washing fluid has been removed at the end of the washing cycle. Conventionally apparatus used to clean the cells of a reaction tray, for example after an incubation period, consists of a washer head with a dispensing tip and an aspirate tip corresponding to each cell. GB-2216260 discloses a device for injecting a fixed quantity of liquid into a reaction tray wherein conductive electrodes are positioned on an injection nozzle and a detecting unit cooperates with the electrodes to detect the surface level of a sample liquid. US-4451433 discloses an automatic chemical reaction analyzer wherein samples are sequentially dispensed into a reaction tray via a first pipetting tube. Reagent solutions are supplied to the reaction trays via a second, conductive, pipetting tube. The liquid levels of the solutions in the reaction trays are detected by a liquid level sensor formed by the second pipetting tube and a conductive electrode. The object of the present invention is to provide a new and improved level sensor and washer unit for an automated immunoassay processing system. Viewed from one aspect, the present invention provides a level sensor for an automated immunoassay processing system, comprising a head mounted for vertical movement, a motor for moving the head, and a positioning circuit for controlling the motor to position the head at specified vertical positions, the head carrying an aspirate tip for aspirating fluid from a reaction cell, the aspirate tip comprising an internal flow passage within and along which first and second electrode means are sequentially positioned, the electrode means being connected to a detector circuit arranged to give an output signal when the electrode means are bridged by fluid, and control means connected to receive the output signal of the detector circuit and arranged to produce an indication of the level of fluid in the reaction cell by reference to a vertical position signal when a detector circuit output signal occurs on the aspirate tip coming into contact with the fluid surface. Viewed from another aspect, the present invention provides a washer unit for an automated immunoassay processing system, comprising a head mounted for vertical movement, a motor for moving the head, and a positioning circuit for controlling the motor to position the head at specified vertical positions, the head carrying a dispensing tip for dispensing washing fluid into a reaction cell and an aspirate tip for aspirating fluid from the cell, the aspirate tip comprising an internal flow passage within and along which first and second electrode means are sequentially positioned, the electrode means being connected to a detector circuit arranged to give an output signal when the electrode means are bridged by fluid, and control meanε connected to receive the output signal of the detector circuit and arranged to produce an indication of the level of fluid in the reaction cell by reference to a vertical position signal when a detector circuit output signal occurs on the aspirate tip coming into contact with the fluid surface. Various embodiments of the present invention will now be described by way of example only, with reference to the accompanying drawings, in which: Figure 1 is a schematic diagram of an automated immunoassay processing system incorporating the invention. Figure 2 is a partial section of a washer head of the apparatus of Figure 1. Figure 3 is a circuit diagram of part of the detector system of a plurality of washer tips. Figure 4 shows the steps in a normal wash cycle employing the invention. Figure 5 shows the steps in a top wash cycle employing the invention. With reference to the drawings, Figure 1 shows a washer head 13 mounted to be driven vertically up and down by a drive means 2 such as a stepper motor. The drive means 2 is controlled by a control means 1 which may include a program-controlled processor. According to a preferred embodiment a matrix of 8 x 3 dispense and aspirate tips 6 are positioned on the washer head 13. The washer head 13 further comprises a printed circuit board (PCB) 5 attached to an insulating block 4. On the upper surface of the insulating block 4 a plenum chamber 9 is provided connected to an aspirate or suction means . An exit passage 10 is provided to allow the removal of fluid drawn along an aspirate fluid path, which includes aspirate tips 6. The aspirate tips 6 are divided into top and bottom sections 6a and 6b as shown in Figure 2. Each top section 6a consists of an upper electrode section inserted into a counterbore within the upper surface of the insulating block 4 and each bottom section 6b consists of a lower electrode section inserted into a corresponding counterbore within the lower surface of the insulating block 4. The upper and lower electrode sections consist preferably of stainless steel fabricated in the form of a tube. The external diameter of the counterbores is larger than the central bore 11. For example, the external diameter of the counterbores may be 1.4 mm whereas the central bore 11 iε preferably 1.0 mm. The internal diameter of the upper and lower sections of the aspirate tips 6 which are inserted into the two counterbores are typically εubεtantially the same diameter aε the internal diameter of the central communicating bore 11. The central communicating bore 11 defines at leaεt a portion of the aspirate fluid path. The depth of the counterbore in the upper surface of the insulating block 4 is typically 20 mm and the depth of the counterbore in the lower surface of the insulating block 4 is typically 30 mm. In uεe, a reaction tray 8 iε vertically spaced below the washer head 13 and the aspirate tips 6. Preferably, the drive meanε 2 conεistε of a stepper motor which can control the vertical displacement of the washer head 13 and aspirate tips 6. According to the preferred embodiment, the stepper motor can control the vertical displacement of the waεher head 13 in steps of 0.1 mm. By way of example, the waεher head may be lowered at a rate of 75 mms "1 . The control means 1 communicates with the PCB 5 of the washer head 13. According to the present invention a fluid or level sensor is provided by arranging two conductive electrode sections, electrically insulated from each other, for example by means of an air gap or other means, along an aspirate fluid path. The air gap is preferably a few millimetres wide. Detector means is connected across the conductive electrode sections to detect the presence of a fluid by detecting a change in conductance between the electrode sections. Since the vertical position of the washer head 13 relative to the reaction tray 8 may be known or determined, for example by the control meanε 1 and/or the drive means 2, then the sensor may function as a level sensor. The upper section 6a of the aspirate tip 6 is held, in use, at substantially zero electrical potential. Preferably, zero potential supply means is provided by a rod or tube 7 inserted through a hole or bore axially disposed through the insulating block 4 and through the PCB 5. The top portion of the tube 7 is electrically connected to the top sections of the other aspirate tips 6 in the chamber 9 by means of a connecting means 3. Preferably, the connecting means consists of a metal spring or the like. On the under surface of the PCB 5 the tube 7 iε electrically connected to the PCB by an electrical connection 12, for example conductive glue or reεin. The lower sections of the aspirate tip 6 also pasε through the PCB 5 and are εimilarly connected to appropriate trackε on the underside of the PCB 5 by means of electrical connections 12. The electrical connections 12 to the aspirate tips 6 are connected according to the preferred embodiment to connectors Jl- 24 as shown in the circuit diagram in Figure 3. The end of the lower section of the aspirate tip 6 may be chamfered, for example by a laser, to form a more defined tip portion. The end of the aspirate tip 6 may also be formed into the shape of a needle. The electrical connections and components on the PCB 5 are poεitioned on the lower surface of the PCB 5. Preferably, a εingle zero potential supply means 7 is provided per row of aεpirate tipε 6. Therefore according to the preferred embodiment (a matrix of 3x8 aεpirate and dispense tips) three zero potential supply means 7 are provided. An electrical circuit thus connected to the upper and lower εections of the aspirate tipε 6 measures the conductance between the upper and lower sectionε of the aspirate tip 6. The circuit generates an output indicating the presence of fluid passing between the two sections of the tip 6 by detecting the change in conductance between the two sections of the aspirate tip 6. Normally most reagents and waεhing fluids are aqueouε based ionic εolutionε and can be detected according to the preεent invention. Figure 3 is a circuit diagram of part of the detector circuit of a conductive washer head 13. According to the preferred embodiment twenty four aspirate tips are connected to the PCB 5 by means of electrical connectionε 12. However, according to other embodiments of the preεent invention a different number of aεpirate tips may be uεed. For example, 8, 16, 32 or 64 aεpirate tips 6 may be used aε desired. Pin 7 (HSO) and Pin 8 (HSl) of connector J25 are set to determine which model of apparatus (namely the number of aspirate tips) is being used. Pin 1 is supplied with + 5V and pin 6 with OV from the control means 1. Pin 2 provides shift out, and pin 3 receives a shift clock. Pin 4 receives shift load and pin 5 the oscillator OSC signal. The period of the oscillator is set at 1-2 ms. This is significantly slower than that of the clock period, but is set at such a value due to delays in measuring the presence of fluid because of polariεation effectε in the aspirate tip 6. The clock input pulseε have a period of subεtantially 1 με and the load input pulεe has subεtantially a εimilar period. On every load pulse the outputs from each of the fluid εensors are stored in shift registers Ul-3. The states of the twenty-four fluid sensors of the preferred embodiment are then cleared from the shift registers Ul-3 after twenty-four consecutive clock pulseε. When the top and bottom εectionε of an aspirate tip 6 are subεtantially insulated from each other, due to the absence of, for example, reagent or wash fluid (or other aqueous based ionic εolution) flowing along the aεpirate fluid path, then the output from the transiεtorε l-24 connected to the bottom sections of the aspirate tips 6 will be the inverεe of the drive εignal OSC. The outputε from the tranεiεtorε Ql-24 are communicated to the shift registerε Ul-3 via data-buses C[1..24] . In the presence of a fluid flowing along the aspirate fluid path (thereby connecting the top and bottom sections of the aspirate tip 6) the transistor will be held off and the output will remain high. Figure 4 showε some of the stepε in a normal wash cycle. Washer head 13 is provided with pairs of dispense tips 14 and aspirate tips 6. The washer head 13 can be moved up and down by means of the mechanical positioning device or drive meanε 2. The drive meanε 2 iε uεed to position the vertical height of the dispense 14 and aspirate 6 tipε as desired during the various stages of a wash cycle. A normal wash cycle comprises the steps of firstly positioning the washer head 13 above a sample or container 8, for example a cell of a reaction tray. The required volume of wash fluid 15 is then dispensed into the container 8 positioned below the dispense tip 14 as shown in step 2. The head 13 and the attached tips 6, 14, are then lowered towards the sample or container 8. Preferably, the aεpirate tip 6 is longer in length than the dispense tip 14. A suction or aspirate means is activated whilst the washer head 13 iε lowered to remove the fluid 15 from the container 8 via the aspirate tip 6. When the detector indicates that fluid haε been sensed, the control means 1 can confirm that the liquid level was correct. As the luid 15 is being removed by the suction or aspirate meanε the washer head 13 is progresεively lowered by drive means 2. The level sensor according to the present invention can determine the level of fluid 15 dispenεed into the container 8 and also check that when the aspirate tip iε lowered all the way to the bottom of the container all of the fluid has been removed. Finally, the washer head 13 and the diεpenεe 14 and aspirate 6 tipε are raiεed clear from the sample or container 8 as shown in step 4 allowing the next step in the processing system to be performed. A second type of wash cycle may alternatively or additionally be performed, known aε a top wash cycle. This is shown in Figure 5. A top wash cycle comprises the steps of firstly positioning the washer head 13 above the container 8 in a similar manner to a normal wash cycle. The washer head 13 is then positioned such that the aspirate tip 6 is set at a level wherein fluid 15 can be aspirated from the container 8 at the same time as fluid 15 is being dispensed from the dispense tip 14 into the container 8. A required quantity of fluid 15 iε then diεpenεed and during this step some of the fluid 15 is aspirated by the aspirate tip 6. When the required sample of fluid 15 has been dispensed the washer head 13 is then lowered by the mechanical positioning means or drive means 2 and the remaining fluid 15 iε removed by the aεpirate tip 6. Following the removal of any remaining fluid 15 the waεher head 13 can be raised clear of the sample 8 (in a similar manner to a normal wash cycle) . During a top wash cycle, the control means 1 can detect the time at which the level sensor detects the presence of fluid 15 flowing along the aspirate path of the aspirate tip 6. The control meanε 1 can then correlate that the diεpense flow rate of fluid from the dispense tip 14 was correct . Towards the end of the third stage of the top or normal waεh cycle, the level sensor can determine whether all the fluid 15 has been aspirated from the container 8 before proceeding to the next step wherein the head 13 is raised clear from the sample 8. In both the normal and top wash cycles a validation step may preferably be performed before any wash fluid is dispensed. The validation step ensures that enough reagent was initially dispenεed into the container 8, for example during a εample preparation or incubation εtage. Thiε iε a εeparate εtep to thoεe εtepε performed during a normal or top waεh cycle. The validation step compriεeε poεitioning the washer head 13 above the container 8 and then lowering the washer head 13 by the mechanical positioning device or drive meanε 2. The aεpirate tip 6 aεpirateε whilεt the washer head 13 iε being lowered. The control means 1 can determine the fluid level and thus whether sufficient reagent or fluid was initially dispensed into the container 8. If the detected fluid level indicateε that an insufficient amount of reagent or other fluid was diεpenεed then an error message may be generated by the control means 1 and the results of that cell can be ignored. According to the present invention, during a normal waεh cycle a validation εtep may be performed after the waεh fluid 15 has been dispensed into the container 8 but before the wash fluid 15 is aspirated out of container 8. The validation step checkε that the correct amount of waεh fluid 15 has been dispenεed into the container 8. The level sensor is able to determine whether it is necessary for a further amount of wash fluid 15 to be diεpensed by the dispense tip 14. Alternatively or additionally, an error signal may be generated by the control means 1. Preferably, the container or reaction tray 8 may be such as to allow the volume of fluid contained therein to be determined by measuring the height or depth of the fluid. For example in the field of Microtiter (RTM) technology a depth of 1 mm corresponds to about 28 μl. The fluid sensor may thus be sensitive to the detection of amounts of about 10 μl of fluid with 0.1mm steps of the drive means. The term "conductance" has been used above in its senεe of inverεe reεiεtance. However, it would be posεible to detect variations in impedance more generally, and in particular a change in capacitance between the electrodes, or a change in combined resistance and capacitance. For measuring capacitance it may be preferable to apply an a.c. signal to the electrodes and to insulate the electrodes on their inside surfaces if it is deεired to exclude reεistive effects through the fluid. The above are only εpecific exampleε of the invention, and various modifications and embodiments of the invention are also within the scope of the invention which is defined by the claims.

Claims: Cl a i ms 1. A level sensor for an automated immunoassay processing syεtem, compriεing a head (13) mounted for vertical movement, a motor (2) for moving the head, and a poεitioning circuit for controlling the motor (2) to poεition the head (13) at specified vertical positions, the head (13) carrying an aspirate tip (6) for aεpira ing fluid (15) from a reaction cell (8) , the aεpirate tip (6) compriεing an internal flow passage within and along which first (6b) and second (6a) electrode means are sequentially positioned, the electrode meanε (6a, 6b) being connected to a detector circuit (5) arranged to give an output εignal when the electrode means (6a, 6b) are bridged by fluid (15) , and control means (1) connected to receive the output signal of the detector circuit (5) and arranged to produce an indication of the level of fluid (15) in the reaction cell (8) by reference to a vertical position signal when a detector circuit output signal occurs on the aspirate tip (6) coming into contact with the fluid surface. 2. A level εensor as claimed in claim 1, wherein the control means (1) compriseε a processor arranged to produce vertical position signalε for controlling the motor (2) in accordance with a stored program. 3. A level sensor as claimed in claim 1 or 2, wherein the electrode means (6a, 6b) comprise two axially spaced metal tubes. 4. A level sensor as claimed in claim 3 , wherein the metal tubes are mounted in an insulating block (4) having a through pasεage (11) which haε a narrower- diameter axially-central portion providing two εhoulderε againεt which the tubes abut . 5. A washer unit for an automated immunoasεay proceεsing syεtem, compriεing a head (13) mounted for vertical movement, a motor (2) for moving the head (13) , and a positioning circuit for controlling the motor (2) to poεition the head (13) at specified vertical poεitionε, the head (13) carrying a dispensing tip (14) for diεpensing washing fluid (15) into a reaction cell (8) and an aspirate tip (6) for aspirating fluid (15) from the cell (8) , the aspirate tip (6) comprising an internal flow passage within and along which first (6b) and second (6a) electrode means are sequentially positioned, the electrode meanε (6a, 6b) being connected to a detector circuit (5) arranged to give an output signal when the electrode means (6a, 6b) are bridged by fluid (15) , and control means (l) connected to receive the output signal of the detector circuit (5) and arranged to produce an indication of the level of fluid (15) in the reaction cell (8) by reference to a vertical position signal when a detector circuit output signal occurs on the aεpirate tip (6) coming into contact with the fluid surface. 6. A waεher unit as claimed in claim 5, wherein the control meanε (1) compriseε a proceεsor arranged to produce vertical poεition signals for controlling the motor (2) in accordance with a stored program. 7. A waεher unit as claimed in claim 5 or 6, wherein the dispensing tip (14) iε arranged to dispense waεhing fluid (15) into a reaction cell (8) with both the diεpensing (14) and aεpirate (6) tipε positioned above the cell (8) , and wherein after the washing fluid (15) is dispensed the aspirate tip (6) is lowered whilst aspirating, the control means (1) being arranged to produce an indication of the level of washing fluid (15) when the aspirate tip (6) reaches the fluid surface, whereby the dispenεing of a correct quantity of washing fluid (15) may be confirmed. 8. A waεher unit as claimed in claim 5 or 6, wherein the aspirate tip (6) is arranged to be positioned within the reaction cell (8) and to aspirate whilst waεhing fluid (15) iε diεpensed from the dispenεe tip (14) , the control meanε (1) being arranged to time the period between commencement of dispensing and detection of fluid (15) by the detector circuit (5) when the fluid level reaches the aspirate tip (6) , to confirm that the fluid (15) is being dispenεed at an acceptable rate. 9. A waεher unit aε claimed in any of claimε 5 to 8, wherein before a waεh cycle the head (13) iε lowered whilst aspirating and the control means (1) produces an indication of the level of a reagent previously diεpenεed, εo that samples having insufficient reagent can be rejected.

Inventors: HIGGS PAUL ANTHONY, INDER DAVID JOHN, LE FEUVRE PETER JOHN, HIGGS, PAUL, ANTHONY, INDER, DAVID, JOHN, LE FEUVRE, PETER, JOHN
Applicants: DYNEX TECHNOLOGIES GUERNSEY LT, HIGGS PAUL ANTHONY, INDER DAVID JOHN, LE FEUVRE PETER JOHN, DYNEX TECHNOLOGIES (GUERNSEY) LTD., HIGGS, PAUL, ANTHONY, INDER, DAVID, JOHN, LE FEUVRE, PETER, JOHN
Application year: 1996
Main classification: G01F23
IPC codes: B01L11, G01F23, G01N35