Classifications

• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
  • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
  • G01N35/1009—Characterised by arrangements for controlling the aspiration or dispense of liquids
  • G01N35/1016—Control of the volume dispensed or introduced
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01F—MEASURING VOLUME, VOLUME FLOW, MASS FLOW OR LIQUID LEVEL; METERING BY VOLUME
  • G01F11/00—Apparatus requiring external operation adapted at each repeated and identical operation to measure and separate a predetermined volume of fluid or fluent solid material from a supply or container, without regard to weight, and to deliver it
  • G01F11/28—Apparatus requiring external operation adapted at each repeated and identical operation to measure and separate a predetermined volume of fluid or fluent solid material from a supply or container, without regard to weight, and to deliver it with stationary measuring chambers having constant volume during measurement
  • G01F11/284—Apparatus requiring external operation adapted at each repeated and identical operation to measure and separate a predetermined volume of fluid or fluent solid material from a supply or container, without regard to weight, and to deliver it with stationary measuring chambers having constant volume during measurement combined with electric level detecting means
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01F—MEASURING VOLUME, VOLUME FLOW, MASS FLOW OR LIQUID LEVEL; METERING BY VOLUME
  • G01F23/00—Indicating or measuring liquid level or level of fluent solid material, e.g. indicating in terms of volume or indicating by means of an alarm
  • G01F23/22—Indicating or measuring liquid level or level of fluent solid material, e.g. indicating in terms of volume or indicating by means of an alarm by measuring physical variables, other than linear dimensions, pressure or weight, dependent on the level to be measured, e.g. by difference of heat transfer of steam or water
  • G01F23/26—Indicating or measuring liquid level or level of fluent solid material, e.g. indicating in terms of volume or indicating by means of an alarm by measuring physical variables, other than linear dimensions, pressure or weight, dependent on the level to be measured, e.g. by difference of heat transfer of steam or water by measuring variations of capacity or inductance of capacitors or inductors arising from the presence of liquid or fluent solid material in the electric or electromagnetic fields
  • G01F23/263—Indicating or measuring liquid level or level of fluent solid material, e.g. indicating in terms of volume or indicating by means of an alarm by measuring physical variables, other than linear dimensions, pressure or weight, dependent on the level to be measured, e.g. by difference of heat transfer of steam or water by measuring variations of capacity or inductance of capacitors or inductors arising from the presence of liquid or fluent solid material in the electric or electromagnetic fields by measuring variations in capacitance of capacitors
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
  • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
  • G01N35/1009—Characterised by arrangements for controlling the aspiration or dispense of liquids
  • G01N2035/1025—Fluid level sensing

Definitions

• the present invention relates to automated biological analysis. More specifically, the present invention relates to a method for measuring the volume of a liquid dispensed in an analysis container by capacity measurement.
• the determination of the quantity of liquid dispensed in the analysis containers is crucial to ensure the relevance of the results obtained. Indeed, at each step of the analysis involved the need to measure the volume of liquid dispensed in the container, but also to ensure the presence of the liquids of interest in said container. This is the case not only with the biological sample to be analyzed, but also with the reagents and the washing solutions used during the analysis. This problem of volumetric management is therefore more generally part of a quality approach aimed at improving, but also at making reliable, the results produced by such analysis automata. Indeed, the reliability and repeatability of the results obtained depend on the accuracy and repeatability of the volumes distributed.
• CE IVD In Vitro Diagnostic
• Some devices are based on an indirect measurement of the volume of liquid. This is particularly the case in analysis automata that do not use a liquid vein; in other words, the automata whose fluidic management is done by means of a pneumatic device. In this case, it is possible to control the pressure of the air contained in the fluidic management circuit.
• the modification of the air pressure profile located between the suction syringe and the liquid being taken or dispensed in the needle makes it possible to evaluate the volume of liquid taken or dispensed.
• a first type of device consists of optical devices, of the transceiver type, which measure the level of liquid through the wall of the container by varying the refractive index difference between the air and a liquid.
• the disadvantage of this type of devices and processes is that they can only be implemented with translucent containers.
• optical devices also use the difference in refractive index between air and liquids to measure the level or volume of liquid in a container.
• these are invasive. Indeed, the transmitter which is generally an optical fiber comes into contact with the liquid. This causes a modification of the refraction of the incident beam and thus a modification of the emergent beam, indicating to the device that it has come into contact with the liquid.
• the transmitter which is generally an optical fiber comes into contact with the liquid. This causes a modification of the refraction of the incident beam and thus a modification of the emergent beam, indicating to the device that it has come into contact with the liquid.
• Such a device is described for example in US Pat. No. 4,809,551.
• US-5,194,747 discloses a device for measuring liquid level through optical means consisting essentially of using a laser diode emitting an incident light beam through an optical fiber and then an optical transmitter, said beam being reflected by the surface of the liquid so that the emergent beam is received by a photoreceptor.
• a phase detector measures the phase difference between the incident beam and the emergent beam.
• a counting scale makes it possible to correlate the phase difference value at the level of the liquid in the container.
• Another major disadvantage of this device is its complexity which, on the one hand, makes its cost price significant and on the other hand, prevents its adaptation to existing PLCs.
• Other devices are based on the principle of weighing the container. Indeed, by performing a differential weighing of the container, the analysis automaton determines whether the container has been filled or emptied and can possibly determine the volume of liquid present in the container.
• this type of weighing device if it performs well enough when the containers are used individually, provides inaccurate information for containers arranged in a rack, ie linked together. In this case, the value obtained can only be an average value on all the containers, which excludes any precise measurement on each of the containers.
• Another type of device is based on magnetic properties. Such a device is described for example in the document EP-AI 014 049. Said device comprises an electromagnet for the non-contact excitation of a wall of the container with an attenuated mechanical oscillation and a probe for the non-contact determination of the oscillation related to the level of liquid contained in the container. The liquid level is determined by the level of attenuation of the oscillation.
• Such a device has the disadvantage of having to be used with metal containers to ensure electro-magnetization phenomena.
• the containers used today are generally made of plastic materials in order to be replaced regularly or even for single use.
• Another type of device consists of ultrasonic measuring devices. This type of device has the advantage of being able to accurately measure the level of liquid in a container. However, in addition to their high cost, these devices are generally quite complex and cumbersome. They further require a reproducible coupling between the ultrasonic probe and the bowl, in order to precisely determine the volume present in the bowl by measuring the flight time of the roundtrip of the ultrasonic wave. This makes it very difficult to adapt to an existing automaton.
• Another type of device consists of devices for measuring the liquid level in a container by capacitive measurement. Indeed, the variation of the capacity between the needle of the device and the container makes it possible to detect the contact of the end of the needle with the surface of the liquid. This method is based on the fact that the capacitance value increases when the needle approaches the liquid, up to a maximum value corresponding to a position where the needle soaks in the liquid. Device and method are described for example in US-4,818,491.
• a significant disadvantage of the droplet volume measuring device described in EP-I 568 415 A2 is that, because of its excessively high sensitivity and necessary for the excessively low volume measurement, it requires an excessively stable electrical environment, obtained especially by setting up a faraday cage.
• a construction is simply inconceivable within a biological analysis machine, which has a changing electrical environment, through the use of a container conveying system; by the fact that the containers may possibly contain different volumes of liquids, prior to dispensing the liquid which is the subject of the volume measurement; in that the electrochemical nature of the liquids used in such automata varies considerably, consequently modifying the electrical environment in which the volume measurement is carried out.
• Such a device if it is very effective, has another disadvantage of being essentially adapted to the measurement of droplets whose volume is relatively low, of the order of picolitre or nanolitre. Indeed, for the measuring method described in EP-I 568 415 A2 can be implemented, it is mandatory that a fluid rupture intervenes between the droplet and the dispensing nozzle. In other words, it is mandatory that the droplet is isolated in space, both the dispensing device and the container that will receive it. This need makes such a device absolutely impossible not suitable for liquid volume measurements, such as those used in biological analysis machines, which range from several tens of microliters to a few milliliters.
• An object of the present invention is therefore to provide an efficient and robust method for measuring the variable volumes of liquids, in particular biological samples, distributed in a container.
• Another object of the present invention is to provide a method for measuring the volume of a liquid dispensed in a container, which is able to identify the presence of bubbles in the liquid, thus distorting the volume dispensed.
• Another object of the present invention is to provide a method of measuring the volume of a liquid dispensed into a container, enabling measurements to be made without lengthening the sample distribution time.
• said method comprising the following steps: a) positioning said suction / discharge device vertically above said container, at a distance d from the bottom of the container or from the surface of the liquid present in the container; b) Trigger the continuous measurement of the capacitance values between the end of the needle of the suction / discharge device and the assembly constituted by the container, the chassis of the analysis automaton and possibly the liquid present in the container; said value being considered as the base value B; c) Trigger the distribution of the liquid in the container with the suction / discharge device, so that the container and the needle of the suction / discharge device is in fluid connection throughout the distribution; d) Measure the period t during which the capacitance values between the end of the needle of the suction / discharge device and the assembly constituted by the container, the chassis of the analysis automaton and possibly the liquid present in the container are greater than a threshold value S; and e) calculating the volume of liquid dispensed into the container by multiplying the period value t obtained in step
• fluidic connection is meant that the needle of the suction / discharge device and the container are connected by a vein or fluidic column formed by the discharge of the liquid from the suction / discharge device into the container.
• the distribution of liquid must be regular and continuous, so that the distributed liquid column makes the connection between the free end of the needle of the suction / discharge device and the container receiving the liquid or liquid already contained in the container.
• the concept of fluidic connection should not be interpreted as a possibility that the free end needle of the suction / discharge device soaks in the liquid previously in the container or just spilled.
• the method according to the invention comprises an additional step c '), subsequent to step c), of moving the suction / discharge device along a vertical axis in order to maintain the distance d between the end of the needle and the surface of the liquid being dispensed.
• the value of d is a function of the volume of liquid to be dispensed into the container.
• the value of d is determined to ensure that the time during which the needle of the suction / discharge device and the container are in fluid connection, is as large as possible.
• the value of the flow rate is a single average value.
• the value of the flow rate is a variable value during the period of time t.
• the value of the flow rate used is the actual value of the flow rate at each capacity measurement. This takes into account the ramps of acceleration and deceleration of the suction device - discharge.
• the method according to the invention further comprises an additional step occurring after step b) of determining, prior to distribution, whether the container contains a residual liquid volume.
• the base value is compared with a reference value corresponding to the capacitance value between the end of the needle of the suction / discharge device and the assembly consisting of the empty container of any liquid and the frame. of the analysis automaton.
• Figures IA and IB show a schematic view of the system for implementing the method according to the invention.
• Figure 2 shows a graph showing the capacitive detection over time, when dispensing two volumes of liquid.
• Figures 3A, 3B and 3C show a flowchart of the method of measuring the volume of liquid dispensed into a container, according to two different embodiments.
• Figure 4 is a graph showing the influence on the capacitive detection of the presence of a residual volume of liquid in the container before dispensing.
• FIG. 5 represents a graph showing the discrimination between the distribution of a first volume of 150 ⁇ l of liquid (water) and the distribution of a first volume of 150 ⁇ l of air
• FIG. 1 The system for implementing the method according to the invention is shown in FIG.
• This suction device is the one conventionally used in an analysis automaton.
• the analysis automaton considered is an immunoassay automaton, such as that sold by the Applicant under the trademark VIDIA®.
• the suction / discharge device 10 consists mainly of a dispensing syringe 12 fluidly connected to a dispensing needle 16, by means of a pipe 14.
• the dispensing needle 16 is positioned in line with a container 18 in which the liquid 17 of interest is to be dispensed.
• This liquid of interest 17 may be a sample to be analyzed. It may also be an analytical reagent or a washing liquid.
• the container 18 may furthermore contain or not a residual liquid. In this case, it contains a residual liquid 20.
• Such a residual liquid may, for example, consist of the sample to be analyzed.
• the dispensed liquid may be an analytical reagent.
• the dispensing needle 16 is connected in series with a capacitive level detection device 22, comprising an electrical resistance R.
• the capacitive level detection device 22 is connected to the ground 24.
• the device 22 uses an RC-type oscillator comprising the resistor R and a capacitor C, referenced 26, the first armature of which consists of the needle 16, the liquid 17 and the liquid 20 during dispensing, and the second armature, by the chassis 28 of the analysis automaton, connected to ground 24.
• the dielectric is constituted either by air in outside the distribution period of the liquid 17 and the container 18, either by the liquid 17 during dispensing and the container 18. It follows that the oscillation frequency of the RC oscillator is directly dependent on the value of the capacity 26. From the frequency, it is possible to obtain the value of period t in microseconds ( ⁇ s).
• the principle of the method according to the invention is then as follows:
• the capacity 26 measured is that of air.
• the value of this capacity is by definition relatively low (of the order of picofarad (pF)).
• FIG. 2 represents a capacitive detection graph showing the evolution over time of the period obtained from the measurement of the capacitance 26 by the capacitive level detection device 22. It should be noted that the axis of abscissa does not represent time in intrinsic values but in number of measurement samples, for example every 300 ⁇ s. In addition, the value 0 of the abscissa is on the right.
• the first event identifiable on the graph is referenced 40. Indeed, while the value of the period is stable, there is a sudden increase in the latter. This increase reflects the descent into the container of the dispensing needle. Indeed, as explained above, during a fluid dispensing step in a container, the needle is positioned in line with the container, then performs a downward movement in the container. As the needle is lowered into the container, the measured capacitance 26 increases as the container assembly 18, liquid 20, frame 28, and mass 26 approaches. This increase in the capacitance 32 causes a decrease the oscillation frequency of the RC circuit and therefore an increase in the period t, as observed on the graph.
• the second remarkable event on this graph is an increase in the period t in the form of a peak referenced 42.
• This peak comprises a plateau and materializes the distribution of the liquid, typically the sample inside the container.
• a cylindrical jet of liquid is formed creating a physical contact between the needle and the container and causing a significant increase in the measured capacity 26.
• This increase is materialized by an increase significant period t.
• the third remarkable event corresponding to the return to a base value of the period t, referenced 44 and this, before a new peak.
• This one-off reduction of the period t actually materializes the presence in the distribution circuit of the suction / discharge device of an air bubble causing a specific cut of the fluid connection between the needle and the container, when the liquid is expelled from the needle.
• the role of this bubble is in fact, to separate the sample volume, a second volume of liquid which is, in this case, washing liquid.
• the distribution of the washing liquid is also clearly represented on the graph by the second peak 46.
• the width of the peaks is directly correlated to the volume of liquid dispensed. Indeed, the greater the volume of liquid and the more the fluidic connection (or physical contact) between the needle and the container lasts in time, this materializing by a longer duration of maintaining period t at its high value. . It follows that we can deduce directly from the observation of the graph that the volume of washing liquid dispensed into the container is greater than the previously dispensed sample volume.
• Data analysis is performed once the liquid distribution is complete. This analysis is based on the values of period t recorded as a function of time. Thus, the parameters of the data analysis are also taken into account and shown in FIG. 2. In particular, the baseline B, the threshold value S and the maximum value M. are defined on the graph.
• the baseline B is calculated after analysis of a number of measurement points constituting the interval P2, also defined in the graph of Figure 2. For example, 120 consecutive measurement points of the interval P2 are taken into account. account and the average of these 120 points is the value of baseline B.
• the maximum value M is calculated taking into account several maximum values.
• the number of measurement points used to calculate the maximum value M must be large enough to ensure that a high value is not an artifact. Nevertheless, it should not be too important so as not to exceed the total duration of a plateau. Thus, it is reasonable to calculate the maximum value M by, for example, averaging 120 measurement points.
• the threshold value S is, in turn, determined mathematically since it is equal to 40% of the difference between the maximum value M and the value of the baseline B.
• the threshold value S is the value of the period t to from which it is considered that the fluidic connection is actually established.
• the other identifiable parameters on the graph of Figure 2 are the different intervals used to perform the analysis of the data.
• the value Pl is the value constituting the beginning of the area of calculation of the baseline B. This value is here at the end of the liquid distribution phase because it is a period during which the The analysis automaton is paused before starting the next step of the analysis. This period is then conducive to calculate the value of the threshold line.
• the value of P1 may be the 200 th measurement point before the end of the capacity value record. In the case where a measurement is made every 300 ⁇ s, the value Pl is thus located 60 milliseconds (ms) before the end of the recording of capacity values.
• the interval P2 is the interval corresponding to the 120 consecutive measurement points of the period t to calculate the baseline B, one of the limits of this interval being constituted by the value P1.
• the value P12 is the value at the beginning of the range of the distribution range.
• the value of P1 can be constituted by the 2000th measurement point before the end of the recording of capacity values. In the case where a measurement is made every 300 ⁇ s, the value P12 is thus located 600 milliseconds (ms) before the end of the recording of capacity values.
• the value P9 is the value constituting the beginning of the end of distribution zone. In this zone, the measured period values t should always be lower than the threshold value S. In the opposite case, an error is triggered by the analysis automaton.
• P9 value can be formed by the 300 th measuring point before the end of the recording capacity values. In the case where a measurement is made every 300 ⁇ s, the value P9 is thus located 90 milliseconds (ms) before the end of the recording of capacity values.
• the value PlOa is the value corresponding to the beginning of the search interval of the separation bubble when it is supposed to be present.
• the value of PlOa can be constituted by the 800 th measurement point before the end of the recording of capacity values. In the case where a measurement is made every 300 ⁇ s, the PlOa value is therefore located 240 milliseconds (ms) before the end of the recording of capacity values. Once this measurement point value has been reached, the bubble is expected to be detected.
• the interval PlOb is the interval corresponding to the consecutive measurement points used in order to highlight the consecutive decrease of several values of the period t corresponding to the presence of the separation bubble. This interval may for example consist of 180 consecutive measurement points.
• FIG. 3 shows the flowchart of the liquid distribution, data analysis and liquid volume calculation process dispensed into a container by the suction / discharge device.
• a method is implemented on the automaton immunoassay VIDIA® marketed by the applicant.
• the sampling process of the liquid to be dispensed is not described here.
• the needle is positioned in line with the container in which the liquid is to be dispensed. This is constituted by step 50.
• the process of acquiring and recording the capacitance values through the capacitive level sensing device is turned on, in accordance with step 52.
• the needle then begins its descent inside the container until its end is found at a distance d from the surface of the liquid.
• the distance d is dependent on the volume of liquid to be dispensed into the container. It is the system that determines this distance based on the volume that needs to be distributed. This is done in step 54.
• Step 56 consists of the actual dispensing of the liquid into the container.
• the process of acquiring and storing capacity values is stopped at step 57.
• the needle then returns to its initial position outside the container, in line with it, according to step 58.
• the steps 56 and 58 can occur simultaneously. In other words, the needle goes up as and when dispensing the liquid in the container.
• This variant corresponds in fact to a dynamic management of the distribution. The interest of such a management will be explained below, in connection with FIG. 4.
• the analysis automaton displays an error, in accordance with step 64. If the value B is indeed between the minimum value and the maximum value we move on to the next step of the data analysis.
• the next step 66 consists in finding the 120 maximum values in the distribution range, namely between the value P12 and stopping the recording of capacitance values, for the calculation of the maximum value M, such that explained above. Thus, the 120 the highest recorded period values t are retained and the average value is calculated. This value is the maximum value M.
• the algorithm of the analysis automaton compares the value of the baseline B and the maximum value M, in step 68. In particular, it calculates the ratio between the value of the difference between M and B, and the value B. If the value of this ratio is less than 0.05 (ie 5%), the minimum difference tolerated between M and B, the analysis automaton displays an error, in accordance with step 70. Indeed, a difference of less than 5% denotes an anomaly in the liquid distribution or data acquisition process. If the difference between B and M is greater than 5%, the calculation of the threshold value S is carried out in step 72.
• the next step 74 consists in finding the edges in the distribution range, namely between the value P12 and stopping the recording of capacitance values.
• edges it is understood that the threshold value S is crossed by the period of time t, that is to say when the period t passes from a value lower than the threshold value S to a higher value or vice versa.
• step 78 the number of edges F is compared with the value of the maximum number of edges. If the number F is greater than the maximum value, the analysis automaton displays an error, in accordance with step 80.
• too many fronts can mean that the suction / discharge device has sucked and dispensed foam, in which case the volume of liquid dispensed does not match the expected volume.
• the maximum value of the number of fronts depends on the type of liquid and the number of liquid segments distributed in a container. Indeed, it is known from experience that some samples are more conducive than others to foam. Furthermore, it is obvious that if it is envisaged to distribute several liquids in the same container in the same distribution step, through several liquid segments separated by an air bubble, it is expected to detect a number more important fronts.
• step 84 If the number of edges is smaller than the maximum value, in the end of distribution zone, namely between the value P9 and the stopping of the recording of capacity values, it is checked that there is no values of period t which are greater than the threshold value S. This step is intended to confirm that the distribution of the liquid is well completed, which must be the case in the end of distribution zone, and that this is clearly apparent from the values of period t. If this is not the case, the analysis automaton displays an error, in accordance with step 84.
• the following step 86 consists in calculating the width of the separation bubble L. For this, it is of course necessary to wait to find a bubble, since determined by the analysis protocol.
• the number L is compared with step 88, with the reference number corresponding to the minimum number defining the separation bubble.
• the minimum number of period values t less than S is set to 5. Nevertheless, this number depends on the size of the separation bubble that is expected to be identified, the size of the bubble being dependent on the protocol. analysis implemented on the automaton.
• the analysis automaton displays an error, according to step 90. This actually means that the expected bubble has not been found. If the number L is as expected, then calculates the volumes of liquid.
• the first volume Vl of the liquid dispensed before the separation bubble is calculated in step 92, by determining the number of period values t greater than the threshold value S, in the interval between the value P12 and the value P10a. + P10b / 2. As explained above to calculate the volume, it is necessary to count the total time of the period values t greater than the threshold value S. This time is then multiplied at the rate of distribution of the needle, in order to obtain the volume.
• step 94 it is verified that the volume Vl obtained is in agreement with the minimum and maximum tolerance values. If this is not the case, the analysis automaton displays an error, in accordance with step 96.
• the next step 98 is to calculate the second volume V2 of the liquid that has been dispensed after the separation bubble.
• This volume V2 is by determining the number of period values t greater than the threshold value S, in the interval between the value P10a + P10b / 2 and the value P9.
• step 100 it is verified that the volume V2 obtained is in agreement with the minimum and maximum tolerance values. If this is not the case, the analysis automaton displays an error, in accordance with step 102. If this is the case, the value of volumes V1 and V2 is recorded in step 104 in the analysis automaton, which is then ready to proceed to the next step of the analysis protocol.
• step 110 consists in calculating the total volume Vt of the liquid that has been distributed in the container, by determining the number of period values t greater than the threshold value S, in the interval between the P12 values. and P9.
• step 112 it is verified that the volume Vt obtained is in agreement with the minimum and maximum tolerance values. If this is not the case, the analysis automaton displays an error, in accordance with step 114.
• the value of the volume Vt is recorded in step 116 in the analysis automaton, which is then ready to proceed to the next step of the analysis protocol.
• the needle is positioned in the container so that its end is at a distance d from the surface of the liquid and does not move until it comes out of the container.
• This mode of operation may have disadvantages in two specific cases. The first case is that in which the distance d is too large compared to the quantity of liquid to be dispensed. It follows that all the liquid will be distributed in the form of a segment of liquid, whose length will be less than the distance d.
• the needle and the container are not in fluidic connection or physical contact, since the liquid segment once distributed, is found in its fall during a period of time in contact, neither with the needle, nor with the container.
• the capacity variation is then non-existent and it is therefore impossible to measure the volume distributed.
• the distance d is too small compared to the quantity of liquid to be dispensed. It follows that once all the liquid has been dispensed, the end of the needle will soak into the liquid contained in the container. In this case, there will be an increase in capacity due to the fluid connection created between the needle and the container. Nevertheless, because the needle is soaked in the liquid dispensed, the connection fluidic is not broken and therefore there is no decrease in capacity. It is therefore also impossible to measure the volume distributed.
• dynamic distribution management avoids these disadvantages. Indeed, it consists in positioning the end of the needle sufficiently close to the liquid to obtain an optimized distance d, namely a distance such that the fluid connection between the needle and the container is established as soon as possible once initiated distribution. The needle goes up as the distribution, linearly, to ensure the rupture of the fluid connection at the end of distribution.
• Figure 4 relates to a graph showing the influence on the capacitive detection of a residual volume of liquid present in the container before distribution.
• the residual volume is here 77 ⁇ l.
• dashed curve the value of the period increases when the needle goes down into the container, as explained above.
• the presence of a volume of residual liquid curve in solid line
• the method according to the invention therefore makes it possible to check, if not quantitatively, at least qualitatively, the presence or absence of a residual volume of liquid in the container before dispensing.
• Figure 5 relates to a graph showing the discrimination between the distribution of a first volume of 150 ⁇ l of liquid (water) and the distribution of a first volume of 150 ⁇ l of air. This distribution is followed by a distribution of a volume of 30 ⁇ l second liquid, which is a washing solution. The curve in solid line shows the distribution of the air. At first, the increase in the period between
• the method according to the invention therefore makes it possible to measure in a relatively precise and reliable manner the volume of the liquids distributed by the suction / discharge device of an analysis automaton, inside a container. Moreover, this method can very easily be implemented in an analysis automaton having a capacitive detection system of the level of liquid to be sampled.

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