CA2183639C - Method for sucking/determining liquid and pipetting device driven and controlled according to method - Google Patents
Method for sucking/determining liquid and pipetting device driven and controlled according to method Download PDFInfo
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- CA2183639C CA2183639C CA002183639A CA2183639A CA2183639C CA 2183639 C CA2183639 C CA 2183639C CA 002183639 A CA002183639 A CA 002183639A CA 2183639 A CA2183639 A CA 2183639A CA 2183639 C CA2183639 C CA 2183639C
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Abstract
In the present invention, a disposable tip or a tip of a cleaning system is attached to a lower edge section of a nozzle, and the nozzle detects a liquid level by receiving fluctuation of light close to the disposable tip or to an opening section at a lower end of the tip in the cleaning system, for instance, light reflected from the liquid surface. In the present invention, not only the liquid level is detected, but also a liquid is filled in the disposable tip or the tip of a cleaning system detachably attached to the nozzle, light is passed through the liquid in the disposable. tip or the tip of a cleaning system, and a change in light amount of the sucked liquid is detected, so that, for instance, a suction rate of the liquid, transparency thereof, contaminated by bubbles therein, clogging and a state wherein water has been exhausted are determined.
Description
METHOD FOR SUChING/DI:TERMINING LIQUID AND PIPETTING DEVICE
DRIVEN AIVD COI\fTROLLED ACCORDING TO METHOD
TECHNICAL FIELD
The present invention relates to an entirely new method for sucking/determining the level of a liquid and to a pipetting; device driven and controlled according to the method.
and more particularly to a method for sucking/detertnining the level of a liquid in which driving required for upward/downward movement of a nozzle for sucking a liquid such as a sample for a blood serum and a reagent as well as for pipetting a liquid to cylinders each for sucking and discharging ~:he liquid is accurately controlled, so that a liquid level and a sucking rate of a liquid by the nozzle, and contamination of foreign matters therein such as bubbles or fibrins or the like in the liquid can accurately be detected, as well as to a pipetting device driven an<i controllled according to the method.
BACKGROUND ART
Generally, important matters .required for enhancing pipetting precision are to detect a level of a blood serum sample and a reagent or similar liquid, to measure a pipetting rate thereof, to measure an absolute Sucking rate thereof, to adhere the liquid to the outside of the nozzle, and to detect contamination thereof by foreign matters such as bubbles and fibrins.
For this reason, conventionally, a method has been employed, in which an electrode is immersed in the liquid together with the nozzle and the liquid level is detected according to a conductive state with the; electrode so that an inserting rate (distance) of the nozzle to the liquid is controlled, but in the case of this method, the electrode must be immersed into the liquid, so that the electrode must be washed after each measurement thereof to prevent cross contamination, and as a result, there have been such problems us that a device Doc. No 76-4 CA PCT Patent becomes complicated, and that size and cost of the device increase.
Then, recently a method of detecting a liquid level using a pressure sensor was proposed. In this method, a sucking pressure of the nozzle when a vapor is sucked is different from that when a liquid is sucked, so that the liquid level is detected by detecting the difference between the pressure's, whereby an inserting rate (distance) of the nozzle to the liquid is controlled, and for this reason only the nozzle is contacted with the liquid, and the method has such advantages as that a cleaning function is not required, which makes it possible to simplify the device as well as to reduce the costs.
However, the method of detecting a liquid level using a pressure sensor has several problems such as that the resolution is low and the sensitivity is not high, and also that the method is easily affected by an atmospheric pressure as well as by pressure change due to the sucked air, and also affected by vibrations generated due to upward/downward movement of the nozzle a~; well as by a noise of the pipetting device itself or a change of a voltage, and for this reason malfunction thereof occurs quite often, and the reliability thereof as a measuring means is quite low.
An optical liquid level detecting means is far more effective as a means to solve the problems as described above. Various means in which both an optical fiber for irradiating light therethrough and an optical fiber for receiving light are disposed outside the nozzle.
have been proposed for the liquid level detecting methods based on the conventional technology.
However, in the liquid level detecting means using light for detecting a liquid level based on the conventional technology, in which both a fiber for irradiating light therethrough and an optical fiber for receiving light are provided outside the nozzle for catching reflected light from a liquid level with the optical fiber for receiving light to detect the level thereby. These fibers are inserted in parallel to each other together with the nozzle into a vessel for a liquid. For this reason it cannot be denied that the method has a Doc. No 76-4 CA PCT Patent possibility of cross contamination caused by the fiber contacting with the liquid adhered to the wall surface of the vessel for a liquid. Moreover, the amount of light caught by the optical fiber for receiving light is extremely small, which makes it difficult to accurately detect a liquid level. In addition the extremely minute control is required, which is difficult because there also occur some cases where a timing for receiving the reflected light is shifted or light cannot be received by the fact that the liquid level becomes slightly wavy due to vibrations of the device.
The present invention was made to solve the problems as described above, and it is an object of the present invention to provide an entirely new method of sucking/determining the level of a liquid, including, for instance, detection of a liquid level in which a light receiving body is provided. in a nozzle, and fluctuation of light in a disposable tip such as a pipetting tip or in an opening section at the lower end of a tip of a cleaning system are detected thereby from the ;side of the nozzle under circumstances similar to seeing the other opening section from one end of a tunnel, so that it is possible to extremely sensitively detect a liquid level, contamination by foreign matters therein, or an interface between liquids each having a different color without being affected by the wavy liquid level, as well as to provide a pipetting device driven and controlled according to the method.
Namely, a basic principle of the present invention is characterized in that the various types of detecting operation are carried out by catching a moment as if a light instantly changed shows fluctuation in a flash when a substance near to (or sucked into) a space cut off from the outside of the environment is changed, for instance, from vapor to liquid.
SUMMARY OF THE INVENTION
Accordingly, the present invention provides a method for suckina/determinin~
the level of a liquid contained in a vessel by means of a nozzle, comprising the steps of:
Doc. No 76-4 CA PCT P~ncnt positioning a light receiver inside the nozzle; and receiving a light irradiation proceeding from the liquid at or near an opening located at a lower end of a dispos;zble tip or a tip of a cleaning system attached to the lower end of said nozzle through a space defined by the said disposable tip or the tip of the cleaning system and entering into the lower end of said nozzle, and detecting fluctuation of said received light irradiation.
Accordingly, the prf~sent invention provides a method for sucking/determinin~
the level of a liquid contained in a vessel by means of a nozzle, comprising the steps of:
providing a light receiver; and receiving light irradiation proceeding from the liquid at or near an opening located at a lower end of a disposable tip or a tip of a cleaning system attached to the lower end of said nozzle through a space defined by the said disposable tip or the tip of the cleaning system and entering into the lower end of said nozzle, and detecting fluctuation of said received light irradiation, wherein the light receiver is not positioned exteriorly of the disposable tip or on an outer side of the nozzle.
Accordingly, the prc;sent invention provides a pipette device, in which the driving force required for pipettinL; a liquid. to a cylinder, for changing the relative position between said cylinder and said nozzle upward/downward, and for sucking/discharginl a liquid is controlled, comprising:
a nozzle having an opening section located at a lower end thereof;
a disposable tip or a tip of a cleaning system having a first, upper end attached to the lower end of said nozzle a:nd having a second, lower end adapted to suck liduid thereinto:
a light receiver positioned inside the nozzle for receiving light proceeding from the liquid at or near the opening of said lower end of said disposable tip or said tip of a a Doc. No 76-4 CA PCT Patent cleaning system and entering into the opening section of said nozzle; and a light detector for detecting fluctuations of said received light.
To achieve the obje<;t as described above, in the method of sucking/determining the level of a liquid according to the present invention, it is essential to detect variations of lights caused by a liquid accommodated in the vessel with the nozzle for sucking the liquid.
In the present invention, a disposable tip or a tip of a cleaning system is attached to a lower edge section of a nozzle, and the nozzle detects a liquid level by receiving tluctuation of light close to the disposable tip or to an opening section at a lower end of the tip in the cleaning system, for instance, light reflected from the liquid surface.
Furthermore, in the present invention, not only the liquid level is detected, but also a liquid is filled in the disposable tip or the tip of a cleaning system detachably attached to the nozzle, light is passed through the liquid in the disposable tip or the tip of a cleaning system, and a change in light amount of the sucked liquid is detected, so that, for instance, a suction rate of the liquid, v~ransparency thereof, contamination by bubbles therein, clogging and a state wherein water has been exhausted are determined.
And furthermore, in the present invention, fluctuation of light wavelength can be detected and a change of color is checked by the nozzle, whereby a liduid level can also be detected. The color change can be c:letected through the liquid according to the nozzle, to detect a color of the colored vessel accommodating a liquid therein.
Alternatively, the color change can be detected through the liquid according to the nozzle, to detect a color of a rack or a color of a holder, in which a transparent vessel accommodating a liquid therein is vertically provided. It is needless to say that detection of color change herein includes detecting an interface on which layers are separated by identifying a color of a blood clot or a blood coagulant in a process, fc>r instance, in which the nozzle is movin~~
downward while sucking a blood serum.
Doc. No 76-4 CA PCT Patent In the present invention, the light is not limited to a case of light which is directly received from the disposar~le tip or from the opening section at the lower end of the tip of a cleaning system attached to the nozzle, and, for instance, light may be irradiated or received through a transparent disposable tip or a tip of a cleaning system.
In the present invention, it is desirable that the nozzle itself is formed with a light transmitting material in a tubular :form, or only the lower edge section thereof is formed with the light transparent material, or a bundle of optical fibers are provided therein.
In this case, it is desirable that a lens body is provided in the tip section of a disposable tip or a tip of a cleaning system in the nozzle, for instance, in a slightly lower side than the opening section in the lower end of the disposable tip or the lower edge thereof, so that the lens can be focused at a position where fluctuation of an amount of received light can be checked with high precision. The lens may be used depending on the form or length of the tip, diameter of the opening section, light-proof property or the like.
and in this case, the lens may be provided in any of a light irradiating section and/or a light receiving section, and a concave lens may be used as well as a convex lens, or a plurality of concave and convex lenses may be combined to be used.
In the present invention, light is supplied to a liquid accommodated in a vessel through the nozzle itself or through a fiber for light irradiation and a light receiving fiber each provided inside the nozzle, or is supplied from the outside of the nozzle.
A supply of light from the outside of the nozzle includes irradiation of IiQht from the outside of a transparent vessel for containing a liquid to said liquid, or irradiation of light to a liquid through a disposable tip or a tip of a cleaning system in addition to irradiation of light from an optical fiber provided near the outside of the nozzle to the liquid. It is needless to say that, irradiation of light is not limited to a case where light is irradiated continuously, but light may be irradiated in a pulsed mode.
Doc. No 76-4 CA PCT Patent Data obtained by the method for sucking/determining the level of a liquid having the construction as described above is preferably used as data for controlling a pipetting device in which driving required for pipetaing a liquid to cylinders for moving upwarcl/downward the nozzle as well as for sucking/discharging a liquid is controlled.
BRIEF DESCRIPTION O:F DRAWINGS
Fig. 1 is an explanatory view showing schematic configuration of a pipetting device according to a first embod~.ment of the present invention;
Fig. 2 is an explanatory view showing schematic configuration of a pipetting device according to a second embodiment of the present invention;
Fig. 3 is an explanatory view showing schematic configuration of a pipetting device according to a third emboa.iment of the present invention;
Fig. 4 is a cross-sectional view showing a state in which a lens body is provided in the light irradiating body and a light receiving body in the pipetting device according to a fourth embodiment of the ~~resent invention;
Fig. 5 is an explanatory view showing schematic configuration of a pipetting device according to a fifth embodiment of the present invention:
Fig. 6 is an explanatory view showing a schematic configuration of a pipettin;~ device according to a sixth embodiment of the present invention;
Fig. 7 is an explanatory view showing schematic configuration of a pipetting device according to a seventh embodiment of the present invention;
Fig. 8 is an explanatory transverse sectional view showing a level (a surface area) of a Doc. No 76-4 CA PCT Patent liquid to be sucked in a case where it is detected whether a sucked amount of liduid is sufficient or not with the pipetting device according to an eighth embodiment of the present tnventton;
Fig. 9 is an explanatory transverse sectional view showing a state of the surface of a sucked liquid when contamination of a liquid by foreign matters contained therein is detected with the pipetting device according to a ninth embodiment of the present invention;
Fig. 10 is an explanatory view showing a transmission path for light when a cleaning tip of the pipetting device according to a tenth embodiment of the present invention is empty; and Fig. 11 is an explanatory view showing a transmission path for light when the inside of the cleaning tip of the pipetting device is filled with a cleaning liquid.
BEST MODE FOR CARF;YING C>UT INVENTION
Detailed description is made for embodiments of the present invention with reference to the related drawings.
Fig. 1 shows a schematic configuration of a pipetting device to which the method for sucking/determining the lt~vel of a liquid according to the first embodiment of the present invention is applied, arid the pipetting device basically comprises a nozzle 2 in communication with and connected to a cylinder 1; an arm 3 for holding the nozzle 2; a drive mechanism 4 for moving the arm 3 upward and downward; a motor 5 for operatin~T
the drive mechanism 4; a, driving circuit 6 for controlling regular/reverse rotation of the motor 5; and a disposable tip 8 detachably attached to the lower edge section 7 of the nozzle 2.
Doc. No 76-4 CA PCT f'atcnt The nozzle 2 is moved downward at a specified position by the drive mechanism, the liquid level WL is detected by a liquid level detecting mechanism described later, then a liquid 10 such as a serum or a reagent accommodated in a vessel 9 is sucked, and then the pipetting device moves upward to discharge the sucked liduid to another vessel (not shown herein). It should be noce:d that each of the basic configurations of the pipetting devices according to the present invention is the same as that which is well known so lon;~ as a particular mention is nor made in the present specification, so that detailed description thereof is omitted herein.
In the nozzle 2, a bore hole 2a through which a liquid is passed along the longitudinal direction in the center section of the nozzle 2 constructed the same as for a nozzle based on the conventional technology is formed, the upper edge section of the bore hole ?a is in communication with and connected to the cylinder 1, and at the same time in the nozzle 2.
the liquid level detecting mechanism comprising a light irradiating body I 1 having yn optical fiber or a bundle of more than two optical fibers and a light receiving body 12 is incorporated, and the lower edge sections of the light irradiating body I 1 and of the light receiving body 12 are arranged each in its exposed state in the bottom surface of the lower edge section 7 in the nozzle 2 formed in a concave shape.
Connected to the upper edge section of the light irradiating body 1 1 is a light emitting section 13 for emitting and supplying light. The light emitting section 13 supplies light to the light irradiating body 11, the light irradiated from the. lower edge section of the light irradiating body 11 is reflected on the liquid surface WL and is received by the light receiving body 12, then the received and reflected light is converted to a voltage by a photoelectric converting section l~ connected to the upper edge section of the light receiving body 12, a signal for the converted voltage value is sent to an A/D
converter 1 ~
for converting it to a digit;zl signal, the digital signal from the A/D
converter 1 > is received by the control section 16 (e.g. microcomputer) for executing various types of controlling.
and the data for a control signal outputted from the control section 16 is displayed on a Doc. No 76-4 CA PCT Pacnt display means 21 comprising a CRT or the like.
The control section l6 comprises an input interface 17 for receiving a digital data signal from the A/D converter 15; a ROM 18 for storing therein a program required for computing an outputted signal; a CPU 19 for executing a specified computing according to a program stored in the ROM 18; a RAM 20 for temporarily storing therein a result of computing or data; an output interface 22 for outputting a control signal to various objects to be controlled or to the display me°ans 21 in the device; and a timer 23. It should be noted that the CPU 19 previously stores therein, for instance, specified values or predetermined values identifying a reflected state of light, executes computing and determining such as comparing the specified values or the predetermined values to measured values, anti transmits an instruction for driving; and controlling each of the mechanisms aceordin~ to the determination.
Intrusion of light from outside or leakage of light transmitted through light irradiating body 11 and light receiving body 12 can be prevented without fail by cutting off light with light-proof film Layers in which the peripheral surface of the nozzle 2 and an internal peripheral surface of the bore hole 2a, or a peripheral surface of the light irradiatinU body 11 and the light receiving body 12 are subjected to black coloring or the like or to mirroring, respectively, so that a clear light signal without any noise can be transmitted.
which makes it possible to control more smoothly the control section. It is needless to say that each of the lower edge sections of the light irradiating body 1 1 and light receiving body 12 is formed, for instance, to a concave lens form, and also formed to a form in which the transmitted light is focused to near the opening at the lower end section of the disposable tip 8, and the light reflected on the liquid surface enters into the nozzle 2 for being detected.
Next, a description is made. for operations of detecting a liquid level in the pipetting device constructed as described above.
Doc. No 76-4 CA PCT Patent When liquid level dt°tection is fed to the control section l6. the control section 16 outputs a control signal to the light emitting section 13, and the light emitting section 13 supplies light to the light irradiating body 1 1. A supply of the light is executed continuously or executed by blinking it at certain time intervals. Then, simultaneously when the light is supplied, the control section 16 also outputs a control signal to the driving circuit 6, and the driving circuit 6 moves the arm 3 downward into the vessel 9 containing a liquid by means of motor 5. Further, the c~~ntrol section 16 starts moving the arm downward and the tuner 23 incorporated therein starts counting.
In association with the downward movement of the arm 3, the light irradiated from the light irradiating body :l I into a disposable tip 8 is, as shown in Fig. l , irradiated from the opening section 8a at the lowt~r end thereof onto a liquid surface WL, and the light reflected on the liquid surface WL, reenters from the opening section 8a at the lower end into the disposable tip 8 and is received by the light receiving body 12.
Namely, the light outputted from the opening section 8a at the lower end of the disposable tip 8 through the light irradiating body 11 and irradiated to the liquid surface WL, when the opening section 8a at the lower end thereof is above the liquid surface, is reflected on the liquid surface WL, or passes under the liduid surface, so that the light hardly returns to the opening 8a at the lower end thereof, and for this reason, the amount of light received by the light receiving body 12 is at a low level.
The amount of light received by the light receiving body 12 while the disposable tip 8 is moving downward to a certain position does not change much.
Then, when the disposable tip 8 has moved downward to a certain position. and light exiting from the opening ,section 8~a at the lower end thereof through the light irradiating body 11 and irradiated to the liquid surface WL is reflected on the liquid surface WL and again received into the disposable tip 8 from the opening section 8a at the lower end thereof, the amount of light in the disposable tip 8 cut off from the outside environment Doc. No 76-4 CA PCT Patent momentarily reaches a high level, so that the light amount at that moment is detected, and the detected amount thereof is compared to a specified value or identified as a predetermined value. In this case, reflected light can be caught at more accurate timing if the cylinder 1 is moved downward 'while sucking an air.
The photoelectric converting section 14 successively converts the change of the light amount during the time described above to a voltage value, and the control section 16 compares the voltage value to the specified value or identifies that as a predetermined value, and immediately terminates the downward movement of the arm 3 and/or the sucking operation by the cylinder 1.
The signal for voltage value obtained as described above is converted to a digital signal with the A/D converter 15, and the fluctuations of a series of voltages can be stored in the control section 16.
The control section 16 measures with the timer 23 a period of time required from start of measurement until a point of time when the maximum voltage value is obtained, and computes a liquid level W:L corresponding to a time previously stored therein with the CPU
19. The data as to whether the liquid level WL has been detected or not is displayed on the display means 21 comprising a CR.T or the like. In the embodiment, however, description was made for a case where: a liquid level was detected by using the timer 23 as an example.
but the present invention is not limited to the case described above. and it is possible to detect a liquid level (po~~ition for driving) by using, for instance, a well known pulse counter or an encoder.
When the liquid level is detected as described above, the control section l6 provides an instruction to the driving circuit 6 to move the arm 3 downward. and the arm 3 descends for the distance instructed by the control section 16 according to the instruction. so that the tip section of the disposable tip r3 i~, inserted into the liquid 10, and a required amount of the liquid 10 in the vessel 9 f~~r a liquid is sucked into the disposable tip 8 with the cylinder 1 l2 Doc. No 76-4 CA PCT Patent sucking the liquid according to an instruction by the control section 16.
In the pipetting device according to the embodiment, as described above, a momentary specified value; or a momentary predetermined value, when fluctuation of the amount of received light reflected on the liquid surface in a space section formed by the disposable tip 8 is extremely different, can be caught as a noiseless clear signal without being affected by the outside. Thus, a liquid level can be detected with high precision, and the nozzle 2 itself is not contacted with the inside surface of the vessel 9 containing a liquid, which makes it possible to prevent cross contamination without fail.
It should be noted that, in the first embodiment, description was made for a case where the lower edge section of the light irradiating body 1 1 is exposed at the lower edge section of the nozzle 2 as an example, but, as described in the second embodiment shown in Fig. 2, the same effect: can be obtained even if the lower edge section of the light irradiating body 11 is led to the outside of the nozzle 2, and light is irradiated from the outside of the nozzle 2, is reflected on the liquid surface WL, and the light reelected thereon is received by the light receiving body 12 provided in the lower edge section of the nozzle 2 through the opening section 8a at the lower end thereof.
Fig. 3 shows the third embodiment according to the present invention, and in this embodiment, the device can also be constructed so that the lower edge sections of the light irradiating body 11 and th~° light receiving body 12 are provided in the side section of the lower edge section 7 of the nozzle 2 in the exposed state respectively, and the disposable tip 8 may be formed with a transparent and photoconductive material, and in that case IiQht irradiated from the light irradiating body I1 passes through the disposable tip 8 and is irradiated to the liquid surFaee WL through the opening section 8a at the lower end of the disposable tip 8, the reflected light again passes through the disposable tip 8. and the amount of the light can be detected with the light receiving body 12.
Fig. 4 shows the fourth embodiment according to the present invention, and in this t3 Doc. No 76-4 CA PCT !'atent embodiment, focusing lenses 24A, 24B are provided each at a positions lower than each of the lower edge sections of the light irradiating body 11 and the light receiving body 12, the light irradiated from the light irradiating body I1 is focused at a point F, on the liquid surface WL, so that a brighter reflected light can be received, and the resolution can further be improved.
The focusing lenses 24A, 24B may be concave lenses or convex lenses, or may be a combination thereof, and also the irradiated light may be focused not only on the point F, on the liquid surface, but also at a center portion F, of the opening section 8a at the lower end of the disposable tip ~~, or at a position F; slightly above the opening section 8a at the lower end of the disposable tip 8 or at any other appropriate position so long as a change in a quantity of received light can be accurately detected. The focusing lenses 24A, 24B may be provided in either one of the light irradiating body 1 1 or the light receiving body 12, but in the present embodiment, a lens is always provided in the side of the light receiving body 12. However, in the present invention, the focusing lens described above may not always be provided therein, and it is quite possible to detect how high the liquid level WL is even if light irradiated from the light irradiating body 1 1 is supplied to the liquid surface without focusing the light thereon.
On the external and internal peripheral surfaces of the tip 8 shown in Fig. 4.
light-proof film layers 25, 2E~ each subjected to black colorii~a or mirroring are formed respectively. By forming the light--proof film layer, ?5, ?6 each on the external peripheral surface as well as on the internal peripheral surface of the disposable tip 8, intrusion of light from the outside into the tip and leakage of light transmitted therethrou~h can be prevented without fail, so that a clear light signal without any noise can be received with the light receiving body 12, and control can be more smoothly provided.
Fig. 5 shows a configuration of a nozzle section in a pipetting device according to a fifth embodiment of the present invention, and the embodiment shows a case where the W
Doc. No 76-4 CA PCT Patent light receiving body 12 is located at the center of the nozzle 2, and is surrounded with a ring-shaped light irradiating body R 1 , with a small gap between the two.
This annularly-shaped gap formed between the light irradiating body 1 1 and light receiving body 12 is in communication with and connected to the cylinder 1 via a suction conduit K.
The other configuration features and effects thereof besides those described above are the same as those in the first embodiment, so the same reference numerals used in the first embodiment are assigned to the portions corresponding thereto in the figure and detailed description thereof is omitted herein.
Fig. 6 shows a pipetting device according to a sixth embodiment of the present invention, and the embodiment shows a case where the invention is applied to a device for pipetting, for instance, a reagent or other liquid accommodated in a bottle 30, in which the light receiving body 12 is provided at the center of the nozzle 2, the light irradiatinyT body 11 formed in a ring shape is proviided outside the light receiving body 12, and a suction conduit K for sucking the liquid in the bottle 30 is provided outside the light irradiating body 11. The other configuration features and effects thereof besides those described above are the same as those in the first embodiment, the same reference numerals used in the first embodiment are assigned to the portions corresponding thereto in the figure and detailed description thereof is omitted herein.
Fig. 7 shows a seven~:h embodiment of the present invention. In this embodiment, the same configuration in the nozzle side is tormed as that in the second embodiment shown in Fig. 2. Light is irradiated from the outside of a colored or transparent vessel 9 containing a liquid, or from the outside of a rack 27 in which the vessel 9 is vertically provided. An amount of light or changt~ of color (light wavelength) is detected through the liquid 10 contained in the vessel 9. It should be noted that detection uccordin~ to color as described above can also be executed in the configuration of the first embodiment.
As described above, as in a case where a light amount is detected, the position of a t;
Doc. No 76-4 CA PCT F'utcnt liquid level WL can be detected evt°n if a change of light wavelength (color) is detected by the light receiving body 12.
By constructing the device so that color can be detected as described above, in a case where two colors of liquid in the vessel 9, for instance, a blood serum and a blood clot or a blood serum, a blood coagulant, and a blood clot are separated into layers by centrifugation and accommodated therein, an interface between a blood serum and other substances can be detected according to a change of the color thereof by slowly moving down the disposable tip 8, which makes it possible to prevent contamination of the tip due to a blood coagulant or a blood clot ei~fectively and without fail.
Fig. 8 shows an eighth embodiment of the present invention. and in this embodiment.
determination can easily bc: made as to whether a sucked amount of a liquid is sufficient or not by detecting a reflected area o~f the liquid 10 or a difference of the reflection height sucked into the disposable. tip 8 according to increase/decrease of the light amount.
Fig. 9 shows a ninth ~°mbodiment of the present invention, and in this embodiment, in a case where a liquid (blood serum) sucked into a disposable tip 8 is contaminated with foreign matters B such as hobbles or fibrins, a light amount received by the light receiving body 12 varies due to the foreign matters B as compared to that in the normal case, so that successive fluctuations of the light amount due to contamination thereof with the foreign matters B can easily be detected to determine whether or not the liquid is contaminated with the foreign matters B.
Fig. 10 and Fig. 11 show a. tenth embodiment of the present invention. and the embodiment shows a case where an engaging section 3? of the tip 31 of a cleaning system having a concave ring shape is formed at the lower edge section of the nozzle ?. the lower edge sections of the light irradiating body 1 I and light receiving body l'_' are each exposed to the inside of the engaging section 32, and light irradiated from the light irradiating body 11 can pass through the engaging section 32 of the nozzle ? and be received by the light Doc. No 76-4 CA PCT Patent receiving body 12 through the tip 31 of a cleaning system formed with a transparent material. The other configuration features and effects thereof besides those described above are substantially the same as those in the first embodiment, so that the same reference numerals used in the first embodiment are assigned to the portions corresponding thereto in the figure, and detailed des~~ription thereof is omitted herein.
When the tip 31 of a cleaning system is detachably attached to the nozzle 2 as described above, and in a case where the inside of the tip 31 is "empty" as shown in Fi~,. lU.
light irradiated from the lil;ht irradiating body 1 1 passes through the tip 3l to the openinyl section of the tip 31 of a cleaninL; system, again passes through the tip 3l to the light receiving body 12, and is r~°ceived thereat, so that determination can be made as to whether the tip 31 is empty (exhausted state) or not by previously measuring an amount of received light in this step.
When the inside of the tip 31 is in a state of being filled with a cleaning liduid as shown in Fig. 11, light irradiated from the light irradiating body 11 passes through the cleaning liquid from the tip 31, again passes through the tip 31, and is received by the light receiving body 12, so that ~3etermination can be made as to whether the tip 31 is filled with a cleaning liquid or not by previous:Ly measuring an amount of received light in this step.
However, in the embodiments shown in Fig. 10 and Fig. 1 1, the outer surface of the tip 31 of a cleaning system should preferably be subjected to the same light-proof processing, because thereby the detecting conditions are not affected from outside of the tip 31, so that the detection the>reof with higher precision can be executed.
As described above, in the present invention. assuming a cane where sucking/determining a liquid level are executed by using light, a nozzle is used as a light receiving body, which makes it possible to detect the level of the liquid sucked by the;
nozzle, without being affe~~ted by any measuring conditions outside the nozzle tip. and in addition the light receiving body is provided in the nozzle, which makes it possible to ~7 Doc. No 76-4 CA PCT Patent prevent without fail generation of cross contamination caused by contacting the light receiving body with a liquid.
In the present invention, not only the liquid level is detected, but also a liquid is tilled in a disposable tip or the tip of a cleaning system detachably attached to the nozzle. Light is passed through the liquid in the disposable tip or the tip of a cleaning system, anti fluctuation of light amount reflected from the sucked liquid is detected, so that, for instance, a sucked amount of the liquid, transparency thereof, contamination by bubbles therein, clogging, and a stage when water has been exhausted are determined.
Furthermore, in the present invention, fluctuation of light wavelength can be detected and a change of color is chf:cked by the nozzle, whereby a liquid level can also be detected.
In the present invention, according to the nozzle a color change can be detected through the liquid to detecC the color of the colored vessel accommodating a liduid therein.
Alternatively, according to the nozzle, the color change can be detected through the liquid to detect a color of a rack or .a color of a holder, in which a transparent vessel accommodating a liquid therein is vertically provided, which makes it possible to detect a liquid level corresponding t:o a change of color environment outside of the disposable tip.
With the present invention, .a color of a blood clot or a blood coagulant can be identified in a process in which the nozzle is moving downward while sucking a blood serum, so that an interface ~~n which layers are separated can easily be detected.
In the present inveni:ion, the invention is not limited to the case wherein light is directly received from the disposable tip or from the opening section of the lower end of the tip of a cleaning system attached to the nozzle. For example, light may be irradiated or received through a transparent disposable tip or a tip of a cleaning system.
In this case, an external surface and/or an internal surface of the disposable tip or the tip of a cleaning system except a portion for transmitting light is coated with a black film or U
Doc. No 76-4 CA PCT Patent a mirror film, or the tip is subjected to a light-proof processing such as coloring, whereby fluctuations of the light can be detecaed with high sensitivity and accuracy.
In the present invention, the nozzle itself is formed with a light transmitting material in a tubular form, and a light irradiating section and a light receiving section are formed in the nozzle formed with the light transparent material, or only the lower edge section thereof is formed with the light transparent material, or optical fibers are provided therein, so that a liquid level can be detected with high precision without any restriction of liquid sucking operations by the nozzle.
With the present invention, the light receiving edge section of the optical fibers is provided in the bottom surface or the side section of the nozzle, so that reflected light entering into the disposable tip can be captured without fail. It is needless to say that the nozzle is desirably subjected to a light-proof processing.
In the present invention, light supplied from the light irradiating body is not necessarily focused. However, depending on conditions such as a form or a length of a tip, a diameter of an opening section, a:nd a light-proof property or the like, a lens body can be disposed at the lower end of a disposable tip or a tip of a cleaning system such that it focuses light at a point where the change of the amount of received light can be checked with high precision. For instance said point could be located at an internal opening section at the lower end of a disposable tip or at a position slightly lower than a lower edge of the disposable tip. In this case, a liquid level can be detected with high precision without any noise therein.
In the present invention, light is supplied to a liquid contained in a vessel by transmitting it continuously through a nozzle or blinking it in a flashes therethrough or by means of optical filters, or is supplied from the outside of the nozzle.
Data obtained by the method for sucking/determinin; the level of a liquid having the ~9 Doc. No 76-4 CA PCT f'atcnt construction as described above are used as data for controlling a pipetting device in which driving required for pipetting a liquid to cylinders for moving the nozzle upward/downward as well as for sucking/discharginl; the level of a liquid is controlled, which makes it possible to realize a high precision control.
INDUSTRIAL APPLICAFtILITY
As described above, the method for slICklIlg/detel'Illlnlng the level of a liduid according to the present invention amd a pipetting device driven and controlled according to the method are applicable for use in procedures such as qualifying, quantifying, separating.
and pipetting a specimen or a sample, identifying a liquid level, and checking whether contents of pipetting are satisfied or not in a clinical inspection. In addition, it is applicable to procedures such as qualifying, quantifying, separating, anti pipetting a used drug.
identifying a liquid level, and checking whether contents of pipetting are satisfied or not in a chemical analysis, to procedures such as qualifying, quantifying, separating, and pipetting a specimen or a sample, identifying a liquid level, and checking whether contents of pipetting are satisfied or not in a DNA analysis, to procedures such tls qualifying.
quantifying, separating, and pipetting a used drug, identifying a liquid level, and checkin'=
whether contents of pipetting are satisfied or not in a system of producing drugs. to procedures such as qualifying, quantifying, separating, and pipetting a specimen or a sample, identifying a liquid level, and checking whether contents of pipetting are satisfied or not in a bacteria and virus inspection, to procedures such as qualifying, quantifyin~l.
separating, and pipetting a specimc°n or a sample. identifying a liquid level, and checking whether contents of pipetting are satisfied or not in a water quality inspection, and furthermore to procedures such as qualifying, quantifying. separating. and pipetting a used drug, identifying a liquid level, and checking whether contents of pipetting are satisfied or not each in color synthesis.
DRIVEN AIVD COI\fTROLLED ACCORDING TO METHOD
TECHNICAL FIELD
The present invention relates to an entirely new method for sucking/determining the level of a liquid and to a pipetting; device driven and controlled according to the method.
and more particularly to a method for sucking/detertnining the level of a liquid in which driving required for upward/downward movement of a nozzle for sucking a liquid such as a sample for a blood serum and a reagent as well as for pipetting a liquid to cylinders each for sucking and discharging ~:he liquid is accurately controlled, so that a liquid level and a sucking rate of a liquid by the nozzle, and contamination of foreign matters therein such as bubbles or fibrins or the like in the liquid can accurately be detected, as well as to a pipetting device driven an<i controllled according to the method.
BACKGROUND ART
Generally, important matters .required for enhancing pipetting precision are to detect a level of a blood serum sample and a reagent or similar liquid, to measure a pipetting rate thereof, to measure an absolute Sucking rate thereof, to adhere the liquid to the outside of the nozzle, and to detect contamination thereof by foreign matters such as bubbles and fibrins.
For this reason, conventionally, a method has been employed, in which an electrode is immersed in the liquid together with the nozzle and the liquid level is detected according to a conductive state with the; electrode so that an inserting rate (distance) of the nozzle to the liquid is controlled, but in the case of this method, the electrode must be immersed into the liquid, so that the electrode must be washed after each measurement thereof to prevent cross contamination, and as a result, there have been such problems us that a device Doc. No 76-4 CA PCT Patent becomes complicated, and that size and cost of the device increase.
Then, recently a method of detecting a liquid level using a pressure sensor was proposed. In this method, a sucking pressure of the nozzle when a vapor is sucked is different from that when a liquid is sucked, so that the liquid level is detected by detecting the difference between the pressure's, whereby an inserting rate (distance) of the nozzle to the liquid is controlled, and for this reason only the nozzle is contacted with the liquid, and the method has such advantages as that a cleaning function is not required, which makes it possible to simplify the device as well as to reduce the costs.
However, the method of detecting a liquid level using a pressure sensor has several problems such as that the resolution is low and the sensitivity is not high, and also that the method is easily affected by an atmospheric pressure as well as by pressure change due to the sucked air, and also affected by vibrations generated due to upward/downward movement of the nozzle a~; well as by a noise of the pipetting device itself or a change of a voltage, and for this reason malfunction thereof occurs quite often, and the reliability thereof as a measuring means is quite low.
An optical liquid level detecting means is far more effective as a means to solve the problems as described above. Various means in which both an optical fiber for irradiating light therethrough and an optical fiber for receiving light are disposed outside the nozzle.
have been proposed for the liquid level detecting methods based on the conventional technology.
However, in the liquid level detecting means using light for detecting a liquid level based on the conventional technology, in which both a fiber for irradiating light therethrough and an optical fiber for receiving light are provided outside the nozzle for catching reflected light from a liquid level with the optical fiber for receiving light to detect the level thereby. These fibers are inserted in parallel to each other together with the nozzle into a vessel for a liquid. For this reason it cannot be denied that the method has a Doc. No 76-4 CA PCT Patent possibility of cross contamination caused by the fiber contacting with the liquid adhered to the wall surface of the vessel for a liquid. Moreover, the amount of light caught by the optical fiber for receiving light is extremely small, which makes it difficult to accurately detect a liquid level. In addition the extremely minute control is required, which is difficult because there also occur some cases where a timing for receiving the reflected light is shifted or light cannot be received by the fact that the liquid level becomes slightly wavy due to vibrations of the device.
The present invention was made to solve the problems as described above, and it is an object of the present invention to provide an entirely new method of sucking/determining the level of a liquid, including, for instance, detection of a liquid level in which a light receiving body is provided. in a nozzle, and fluctuation of light in a disposable tip such as a pipetting tip or in an opening section at the lower end of a tip of a cleaning system are detected thereby from the ;side of the nozzle under circumstances similar to seeing the other opening section from one end of a tunnel, so that it is possible to extremely sensitively detect a liquid level, contamination by foreign matters therein, or an interface between liquids each having a different color without being affected by the wavy liquid level, as well as to provide a pipetting device driven and controlled according to the method.
Namely, a basic principle of the present invention is characterized in that the various types of detecting operation are carried out by catching a moment as if a light instantly changed shows fluctuation in a flash when a substance near to (or sucked into) a space cut off from the outside of the environment is changed, for instance, from vapor to liquid.
SUMMARY OF THE INVENTION
Accordingly, the present invention provides a method for suckina/determinin~
the level of a liquid contained in a vessel by means of a nozzle, comprising the steps of:
Doc. No 76-4 CA PCT P~ncnt positioning a light receiver inside the nozzle; and receiving a light irradiation proceeding from the liquid at or near an opening located at a lower end of a dispos;zble tip or a tip of a cleaning system attached to the lower end of said nozzle through a space defined by the said disposable tip or the tip of the cleaning system and entering into the lower end of said nozzle, and detecting fluctuation of said received light irradiation.
Accordingly, the prf~sent invention provides a method for sucking/determinin~
the level of a liquid contained in a vessel by means of a nozzle, comprising the steps of:
providing a light receiver; and receiving light irradiation proceeding from the liquid at or near an opening located at a lower end of a disposable tip or a tip of a cleaning system attached to the lower end of said nozzle through a space defined by the said disposable tip or the tip of the cleaning system and entering into the lower end of said nozzle, and detecting fluctuation of said received light irradiation, wherein the light receiver is not positioned exteriorly of the disposable tip or on an outer side of the nozzle.
Accordingly, the prc;sent invention provides a pipette device, in which the driving force required for pipettinL; a liquid. to a cylinder, for changing the relative position between said cylinder and said nozzle upward/downward, and for sucking/discharginl a liquid is controlled, comprising:
a nozzle having an opening section located at a lower end thereof;
a disposable tip or a tip of a cleaning system having a first, upper end attached to the lower end of said nozzle a:nd having a second, lower end adapted to suck liduid thereinto:
a light receiver positioned inside the nozzle for receiving light proceeding from the liquid at or near the opening of said lower end of said disposable tip or said tip of a a Doc. No 76-4 CA PCT Patent cleaning system and entering into the opening section of said nozzle; and a light detector for detecting fluctuations of said received light.
To achieve the obje<;t as described above, in the method of sucking/determining the level of a liquid according to the present invention, it is essential to detect variations of lights caused by a liquid accommodated in the vessel with the nozzle for sucking the liquid.
In the present invention, a disposable tip or a tip of a cleaning system is attached to a lower edge section of a nozzle, and the nozzle detects a liquid level by receiving tluctuation of light close to the disposable tip or to an opening section at a lower end of the tip in the cleaning system, for instance, light reflected from the liquid surface.
Furthermore, in the present invention, not only the liquid level is detected, but also a liquid is filled in the disposable tip or the tip of a cleaning system detachably attached to the nozzle, light is passed through the liquid in the disposable tip or the tip of a cleaning system, and a change in light amount of the sucked liquid is detected, so that, for instance, a suction rate of the liquid, v~ransparency thereof, contamination by bubbles therein, clogging and a state wherein water has been exhausted are determined.
And furthermore, in the present invention, fluctuation of light wavelength can be detected and a change of color is checked by the nozzle, whereby a liduid level can also be detected. The color change can be c:letected through the liquid according to the nozzle, to detect a color of the colored vessel accommodating a liquid therein.
Alternatively, the color change can be detected through the liquid according to the nozzle, to detect a color of a rack or a color of a holder, in which a transparent vessel accommodating a liquid therein is vertically provided. It is needless to say that detection of color change herein includes detecting an interface on which layers are separated by identifying a color of a blood clot or a blood coagulant in a process, fc>r instance, in which the nozzle is movin~~
downward while sucking a blood serum.
Doc. No 76-4 CA PCT Patent In the present invention, the light is not limited to a case of light which is directly received from the disposar~le tip or from the opening section at the lower end of the tip of a cleaning system attached to the nozzle, and, for instance, light may be irradiated or received through a transparent disposable tip or a tip of a cleaning system.
In the present invention, it is desirable that the nozzle itself is formed with a light transmitting material in a tubular :form, or only the lower edge section thereof is formed with the light transparent material, or a bundle of optical fibers are provided therein.
In this case, it is desirable that a lens body is provided in the tip section of a disposable tip or a tip of a cleaning system in the nozzle, for instance, in a slightly lower side than the opening section in the lower end of the disposable tip or the lower edge thereof, so that the lens can be focused at a position where fluctuation of an amount of received light can be checked with high precision. The lens may be used depending on the form or length of the tip, diameter of the opening section, light-proof property or the like.
and in this case, the lens may be provided in any of a light irradiating section and/or a light receiving section, and a concave lens may be used as well as a convex lens, or a plurality of concave and convex lenses may be combined to be used.
In the present invention, light is supplied to a liquid accommodated in a vessel through the nozzle itself or through a fiber for light irradiation and a light receiving fiber each provided inside the nozzle, or is supplied from the outside of the nozzle.
A supply of light from the outside of the nozzle includes irradiation of IiQht from the outside of a transparent vessel for containing a liquid to said liquid, or irradiation of light to a liquid through a disposable tip or a tip of a cleaning system in addition to irradiation of light from an optical fiber provided near the outside of the nozzle to the liquid. It is needless to say that, irradiation of light is not limited to a case where light is irradiated continuously, but light may be irradiated in a pulsed mode.
Doc. No 76-4 CA PCT Patent Data obtained by the method for sucking/determining the level of a liquid having the construction as described above is preferably used as data for controlling a pipetting device in which driving required for pipetaing a liquid to cylinders for moving upwarcl/downward the nozzle as well as for sucking/discharging a liquid is controlled.
BRIEF DESCRIPTION O:F DRAWINGS
Fig. 1 is an explanatory view showing schematic configuration of a pipetting device according to a first embod~.ment of the present invention;
Fig. 2 is an explanatory view showing schematic configuration of a pipetting device according to a second embodiment of the present invention;
Fig. 3 is an explanatory view showing schematic configuration of a pipetting device according to a third emboa.iment of the present invention;
Fig. 4 is a cross-sectional view showing a state in which a lens body is provided in the light irradiating body and a light receiving body in the pipetting device according to a fourth embodiment of the ~~resent invention;
Fig. 5 is an explanatory view showing schematic configuration of a pipetting device according to a fifth embodiment of the present invention:
Fig. 6 is an explanatory view showing a schematic configuration of a pipettin;~ device according to a sixth embodiment of the present invention;
Fig. 7 is an explanatory view showing schematic configuration of a pipetting device according to a seventh embodiment of the present invention;
Fig. 8 is an explanatory transverse sectional view showing a level (a surface area) of a Doc. No 76-4 CA PCT Patent liquid to be sucked in a case where it is detected whether a sucked amount of liduid is sufficient or not with the pipetting device according to an eighth embodiment of the present tnventton;
Fig. 9 is an explanatory transverse sectional view showing a state of the surface of a sucked liquid when contamination of a liquid by foreign matters contained therein is detected with the pipetting device according to a ninth embodiment of the present invention;
Fig. 10 is an explanatory view showing a transmission path for light when a cleaning tip of the pipetting device according to a tenth embodiment of the present invention is empty; and Fig. 11 is an explanatory view showing a transmission path for light when the inside of the cleaning tip of the pipetting device is filled with a cleaning liquid.
BEST MODE FOR CARF;YING C>UT INVENTION
Detailed description is made for embodiments of the present invention with reference to the related drawings.
Fig. 1 shows a schematic configuration of a pipetting device to which the method for sucking/determining the lt~vel of a liquid according to the first embodiment of the present invention is applied, arid the pipetting device basically comprises a nozzle 2 in communication with and connected to a cylinder 1; an arm 3 for holding the nozzle 2; a drive mechanism 4 for moving the arm 3 upward and downward; a motor 5 for operatin~T
the drive mechanism 4; a, driving circuit 6 for controlling regular/reverse rotation of the motor 5; and a disposable tip 8 detachably attached to the lower edge section 7 of the nozzle 2.
Doc. No 76-4 CA PCT f'atcnt The nozzle 2 is moved downward at a specified position by the drive mechanism, the liquid level WL is detected by a liquid level detecting mechanism described later, then a liquid 10 such as a serum or a reagent accommodated in a vessel 9 is sucked, and then the pipetting device moves upward to discharge the sucked liduid to another vessel (not shown herein). It should be noce:d that each of the basic configurations of the pipetting devices according to the present invention is the same as that which is well known so lon;~ as a particular mention is nor made in the present specification, so that detailed description thereof is omitted herein.
In the nozzle 2, a bore hole 2a through which a liquid is passed along the longitudinal direction in the center section of the nozzle 2 constructed the same as for a nozzle based on the conventional technology is formed, the upper edge section of the bore hole ?a is in communication with and connected to the cylinder 1, and at the same time in the nozzle 2.
the liquid level detecting mechanism comprising a light irradiating body I 1 having yn optical fiber or a bundle of more than two optical fibers and a light receiving body 12 is incorporated, and the lower edge sections of the light irradiating body I 1 and of the light receiving body 12 are arranged each in its exposed state in the bottom surface of the lower edge section 7 in the nozzle 2 formed in a concave shape.
Connected to the upper edge section of the light irradiating body 1 1 is a light emitting section 13 for emitting and supplying light. The light emitting section 13 supplies light to the light irradiating body 11, the light irradiated from the. lower edge section of the light irradiating body 11 is reflected on the liquid surface WL and is received by the light receiving body 12, then the received and reflected light is converted to a voltage by a photoelectric converting section l~ connected to the upper edge section of the light receiving body 12, a signal for the converted voltage value is sent to an A/D
converter 1 ~
for converting it to a digit;zl signal, the digital signal from the A/D
converter 1 > is received by the control section 16 (e.g. microcomputer) for executing various types of controlling.
and the data for a control signal outputted from the control section 16 is displayed on a Doc. No 76-4 CA PCT Pacnt display means 21 comprising a CRT or the like.
The control section l6 comprises an input interface 17 for receiving a digital data signal from the A/D converter 15; a ROM 18 for storing therein a program required for computing an outputted signal; a CPU 19 for executing a specified computing according to a program stored in the ROM 18; a RAM 20 for temporarily storing therein a result of computing or data; an output interface 22 for outputting a control signal to various objects to be controlled or to the display me°ans 21 in the device; and a timer 23. It should be noted that the CPU 19 previously stores therein, for instance, specified values or predetermined values identifying a reflected state of light, executes computing and determining such as comparing the specified values or the predetermined values to measured values, anti transmits an instruction for driving; and controlling each of the mechanisms aceordin~ to the determination.
Intrusion of light from outside or leakage of light transmitted through light irradiating body 11 and light receiving body 12 can be prevented without fail by cutting off light with light-proof film Layers in which the peripheral surface of the nozzle 2 and an internal peripheral surface of the bore hole 2a, or a peripheral surface of the light irradiatinU body 11 and the light receiving body 12 are subjected to black coloring or the like or to mirroring, respectively, so that a clear light signal without any noise can be transmitted.
which makes it possible to control more smoothly the control section. It is needless to say that each of the lower edge sections of the light irradiating body 1 1 and light receiving body 12 is formed, for instance, to a concave lens form, and also formed to a form in which the transmitted light is focused to near the opening at the lower end section of the disposable tip 8, and the light reflected on the liquid surface enters into the nozzle 2 for being detected.
Next, a description is made. for operations of detecting a liquid level in the pipetting device constructed as described above.
Doc. No 76-4 CA PCT Patent When liquid level dt°tection is fed to the control section l6. the control section 16 outputs a control signal to the light emitting section 13, and the light emitting section 13 supplies light to the light irradiating body 1 1. A supply of the light is executed continuously or executed by blinking it at certain time intervals. Then, simultaneously when the light is supplied, the control section 16 also outputs a control signal to the driving circuit 6, and the driving circuit 6 moves the arm 3 downward into the vessel 9 containing a liquid by means of motor 5. Further, the c~~ntrol section 16 starts moving the arm downward and the tuner 23 incorporated therein starts counting.
In association with the downward movement of the arm 3, the light irradiated from the light irradiating body :l I into a disposable tip 8 is, as shown in Fig. l , irradiated from the opening section 8a at the lowt~r end thereof onto a liquid surface WL, and the light reflected on the liquid surface WL, reenters from the opening section 8a at the lower end into the disposable tip 8 and is received by the light receiving body 12.
Namely, the light outputted from the opening section 8a at the lower end of the disposable tip 8 through the light irradiating body 11 and irradiated to the liquid surface WL, when the opening section 8a at the lower end thereof is above the liquid surface, is reflected on the liquid surface WL, or passes under the liduid surface, so that the light hardly returns to the opening 8a at the lower end thereof, and for this reason, the amount of light received by the light receiving body 12 is at a low level.
The amount of light received by the light receiving body 12 while the disposable tip 8 is moving downward to a certain position does not change much.
Then, when the disposable tip 8 has moved downward to a certain position. and light exiting from the opening ,section 8~a at the lower end thereof through the light irradiating body 11 and irradiated to the liquid surface WL is reflected on the liquid surface WL and again received into the disposable tip 8 from the opening section 8a at the lower end thereof, the amount of light in the disposable tip 8 cut off from the outside environment Doc. No 76-4 CA PCT Patent momentarily reaches a high level, so that the light amount at that moment is detected, and the detected amount thereof is compared to a specified value or identified as a predetermined value. In this case, reflected light can be caught at more accurate timing if the cylinder 1 is moved downward 'while sucking an air.
The photoelectric converting section 14 successively converts the change of the light amount during the time described above to a voltage value, and the control section 16 compares the voltage value to the specified value or identifies that as a predetermined value, and immediately terminates the downward movement of the arm 3 and/or the sucking operation by the cylinder 1.
The signal for voltage value obtained as described above is converted to a digital signal with the A/D converter 15, and the fluctuations of a series of voltages can be stored in the control section 16.
The control section 16 measures with the timer 23 a period of time required from start of measurement until a point of time when the maximum voltage value is obtained, and computes a liquid level W:L corresponding to a time previously stored therein with the CPU
19. The data as to whether the liquid level WL has been detected or not is displayed on the display means 21 comprising a CR.T or the like. In the embodiment, however, description was made for a case where: a liquid level was detected by using the timer 23 as an example.
but the present invention is not limited to the case described above. and it is possible to detect a liquid level (po~~ition for driving) by using, for instance, a well known pulse counter or an encoder.
When the liquid level is detected as described above, the control section l6 provides an instruction to the driving circuit 6 to move the arm 3 downward. and the arm 3 descends for the distance instructed by the control section 16 according to the instruction. so that the tip section of the disposable tip r3 i~, inserted into the liquid 10, and a required amount of the liquid 10 in the vessel 9 f~~r a liquid is sucked into the disposable tip 8 with the cylinder 1 l2 Doc. No 76-4 CA PCT Patent sucking the liquid according to an instruction by the control section 16.
In the pipetting device according to the embodiment, as described above, a momentary specified value; or a momentary predetermined value, when fluctuation of the amount of received light reflected on the liquid surface in a space section formed by the disposable tip 8 is extremely different, can be caught as a noiseless clear signal without being affected by the outside. Thus, a liquid level can be detected with high precision, and the nozzle 2 itself is not contacted with the inside surface of the vessel 9 containing a liquid, which makes it possible to prevent cross contamination without fail.
It should be noted that, in the first embodiment, description was made for a case where the lower edge section of the light irradiating body 1 1 is exposed at the lower edge section of the nozzle 2 as an example, but, as described in the second embodiment shown in Fig. 2, the same effect: can be obtained even if the lower edge section of the light irradiating body 11 is led to the outside of the nozzle 2, and light is irradiated from the outside of the nozzle 2, is reflected on the liquid surface WL, and the light reelected thereon is received by the light receiving body 12 provided in the lower edge section of the nozzle 2 through the opening section 8a at the lower end thereof.
Fig. 3 shows the third embodiment according to the present invention, and in this embodiment, the device can also be constructed so that the lower edge sections of the light irradiating body 11 and th~° light receiving body 12 are provided in the side section of the lower edge section 7 of the nozzle 2 in the exposed state respectively, and the disposable tip 8 may be formed with a transparent and photoconductive material, and in that case IiQht irradiated from the light irradiating body I1 passes through the disposable tip 8 and is irradiated to the liquid surFaee WL through the opening section 8a at the lower end of the disposable tip 8, the reflected light again passes through the disposable tip 8. and the amount of the light can be detected with the light receiving body 12.
Fig. 4 shows the fourth embodiment according to the present invention, and in this t3 Doc. No 76-4 CA PCT !'atent embodiment, focusing lenses 24A, 24B are provided each at a positions lower than each of the lower edge sections of the light irradiating body 11 and the light receiving body 12, the light irradiated from the light irradiating body I1 is focused at a point F, on the liquid surface WL, so that a brighter reflected light can be received, and the resolution can further be improved.
The focusing lenses 24A, 24B may be concave lenses or convex lenses, or may be a combination thereof, and also the irradiated light may be focused not only on the point F, on the liquid surface, but also at a center portion F, of the opening section 8a at the lower end of the disposable tip ~~, or at a position F; slightly above the opening section 8a at the lower end of the disposable tip 8 or at any other appropriate position so long as a change in a quantity of received light can be accurately detected. The focusing lenses 24A, 24B may be provided in either one of the light irradiating body 1 1 or the light receiving body 12, but in the present embodiment, a lens is always provided in the side of the light receiving body 12. However, in the present invention, the focusing lens described above may not always be provided therein, and it is quite possible to detect how high the liquid level WL is even if light irradiated from the light irradiating body 1 1 is supplied to the liquid surface without focusing the light thereon.
On the external and internal peripheral surfaces of the tip 8 shown in Fig. 4.
light-proof film layers 25, 2E~ each subjected to black colorii~a or mirroring are formed respectively. By forming the light--proof film layer, ?5, ?6 each on the external peripheral surface as well as on the internal peripheral surface of the disposable tip 8, intrusion of light from the outside into the tip and leakage of light transmitted therethrou~h can be prevented without fail, so that a clear light signal without any noise can be received with the light receiving body 12, and control can be more smoothly provided.
Fig. 5 shows a configuration of a nozzle section in a pipetting device according to a fifth embodiment of the present invention, and the embodiment shows a case where the W
Doc. No 76-4 CA PCT Patent light receiving body 12 is located at the center of the nozzle 2, and is surrounded with a ring-shaped light irradiating body R 1 , with a small gap between the two.
This annularly-shaped gap formed between the light irradiating body 1 1 and light receiving body 12 is in communication with and connected to the cylinder 1 via a suction conduit K.
The other configuration features and effects thereof besides those described above are the same as those in the first embodiment, so the same reference numerals used in the first embodiment are assigned to the portions corresponding thereto in the figure and detailed description thereof is omitted herein.
Fig. 6 shows a pipetting device according to a sixth embodiment of the present invention, and the embodiment shows a case where the invention is applied to a device for pipetting, for instance, a reagent or other liquid accommodated in a bottle 30, in which the light receiving body 12 is provided at the center of the nozzle 2, the light irradiatinyT body 11 formed in a ring shape is proviided outside the light receiving body 12, and a suction conduit K for sucking the liquid in the bottle 30 is provided outside the light irradiating body 11. The other configuration features and effects thereof besides those described above are the same as those in the first embodiment, the same reference numerals used in the first embodiment are assigned to the portions corresponding thereto in the figure and detailed description thereof is omitted herein.
Fig. 7 shows a seven~:h embodiment of the present invention. In this embodiment, the same configuration in the nozzle side is tormed as that in the second embodiment shown in Fig. 2. Light is irradiated from the outside of a colored or transparent vessel 9 containing a liquid, or from the outside of a rack 27 in which the vessel 9 is vertically provided. An amount of light or changt~ of color (light wavelength) is detected through the liquid 10 contained in the vessel 9. It should be noted that detection uccordin~ to color as described above can also be executed in the configuration of the first embodiment.
As described above, as in a case where a light amount is detected, the position of a t;
Doc. No 76-4 CA PCT F'utcnt liquid level WL can be detected evt°n if a change of light wavelength (color) is detected by the light receiving body 12.
By constructing the device so that color can be detected as described above, in a case where two colors of liquid in the vessel 9, for instance, a blood serum and a blood clot or a blood serum, a blood coagulant, and a blood clot are separated into layers by centrifugation and accommodated therein, an interface between a blood serum and other substances can be detected according to a change of the color thereof by slowly moving down the disposable tip 8, which makes it possible to prevent contamination of the tip due to a blood coagulant or a blood clot ei~fectively and without fail.
Fig. 8 shows an eighth embodiment of the present invention. and in this embodiment.
determination can easily bc: made as to whether a sucked amount of a liquid is sufficient or not by detecting a reflected area o~f the liquid 10 or a difference of the reflection height sucked into the disposable. tip 8 according to increase/decrease of the light amount.
Fig. 9 shows a ninth ~°mbodiment of the present invention, and in this embodiment, in a case where a liquid (blood serum) sucked into a disposable tip 8 is contaminated with foreign matters B such as hobbles or fibrins, a light amount received by the light receiving body 12 varies due to the foreign matters B as compared to that in the normal case, so that successive fluctuations of the light amount due to contamination thereof with the foreign matters B can easily be detected to determine whether or not the liquid is contaminated with the foreign matters B.
Fig. 10 and Fig. 11 show a. tenth embodiment of the present invention. and the embodiment shows a case where an engaging section 3? of the tip 31 of a cleaning system having a concave ring shape is formed at the lower edge section of the nozzle ?. the lower edge sections of the light irradiating body 1 I and light receiving body l'_' are each exposed to the inside of the engaging section 32, and light irradiated from the light irradiating body 11 can pass through the engaging section 32 of the nozzle ? and be received by the light Doc. No 76-4 CA PCT Patent receiving body 12 through the tip 31 of a cleaning system formed with a transparent material. The other configuration features and effects thereof besides those described above are substantially the same as those in the first embodiment, so that the same reference numerals used in the first embodiment are assigned to the portions corresponding thereto in the figure, and detailed des~~ription thereof is omitted herein.
When the tip 31 of a cleaning system is detachably attached to the nozzle 2 as described above, and in a case where the inside of the tip 31 is "empty" as shown in Fi~,. lU.
light irradiated from the lil;ht irradiating body 1 1 passes through the tip 3l to the openinyl section of the tip 31 of a cleaninL; system, again passes through the tip 3l to the light receiving body 12, and is r~°ceived thereat, so that determination can be made as to whether the tip 31 is empty (exhausted state) or not by previously measuring an amount of received light in this step.
When the inside of the tip 31 is in a state of being filled with a cleaning liduid as shown in Fig. 11, light irradiated from the light irradiating body 11 passes through the cleaning liquid from the tip 31, again passes through the tip 31, and is received by the light receiving body 12, so that ~3etermination can be made as to whether the tip 31 is filled with a cleaning liquid or not by previous:Ly measuring an amount of received light in this step.
However, in the embodiments shown in Fig. 10 and Fig. 1 1, the outer surface of the tip 31 of a cleaning system should preferably be subjected to the same light-proof processing, because thereby the detecting conditions are not affected from outside of the tip 31, so that the detection the>reof with higher precision can be executed.
As described above, in the present invention. assuming a cane where sucking/determining a liquid level are executed by using light, a nozzle is used as a light receiving body, which makes it possible to detect the level of the liquid sucked by the;
nozzle, without being affe~~ted by any measuring conditions outside the nozzle tip. and in addition the light receiving body is provided in the nozzle, which makes it possible to ~7 Doc. No 76-4 CA PCT Patent prevent without fail generation of cross contamination caused by contacting the light receiving body with a liquid.
In the present invention, not only the liquid level is detected, but also a liquid is tilled in a disposable tip or the tip of a cleaning system detachably attached to the nozzle. Light is passed through the liquid in the disposable tip or the tip of a cleaning system, anti fluctuation of light amount reflected from the sucked liquid is detected, so that, for instance, a sucked amount of the liquid, transparency thereof, contamination by bubbles therein, clogging, and a stage when water has been exhausted are determined.
Furthermore, in the present invention, fluctuation of light wavelength can be detected and a change of color is chf:cked by the nozzle, whereby a liquid level can also be detected.
In the present invention, according to the nozzle a color change can be detected through the liquid to detecC the color of the colored vessel accommodating a liduid therein.
Alternatively, according to the nozzle, the color change can be detected through the liquid to detect a color of a rack or .a color of a holder, in which a transparent vessel accommodating a liquid therein is vertically provided, which makes it possible to detect a liquid level corresponding t:o a change of color environment outside of the disposable tip.
With the present invention, .a color of a blood clot or a blood coagulant can be identified in a process in which the nozzle is moving downward while sucking a blood serum, so that an interface ~~n which layers are separated can easily be detected.
In the present inveni:ion, the invention is not limited to the case wherein light is directly received from the disposable tip or from the opening section of the lower end of the tip of a cleaning system attached to the nozzle. For example, light may be irradiated or received through a transparent disposable tip or a tip of a cleaning system.
In this case, an external surface and/or an internal surface of the disposable tip or the tip of a cleaning system except a portion for transmitting light is coated with a black film or U
Doc. No 76-4 CA PCT Patent a mirror film, or the tip is subjected to a light-proof processing such as coloring, whereby fluctuations of the light can be detecaed with high sensitivity and accuracy.
In the present invention, the nozzle itself is formed with a light transmitting material in a tubular form, and a light irradiating section and a light receiving section are formed in the nozzle formed with the light transparent material, or only the lower edge section thereof is formed with the light transparent material, or optical fibers are provided therein, so that a liquid level can be detected with high precision without any restriction of liquid sucking operations by the nozzle.
With the present invention, the light receiving edge section of the optical fibers is provided in the bottom surface or the side section of the nozzle, so that reflected light entering into the disposable tip can be captured without fail. It is needless to say that the nozzle is desirably subjected to a light-proof processing.
In the present invention, light supplied from the light irradiating body is not necessarily focused. However, depending on conditions such as a form or a length of a tip, a diameter of an opening section, a:nd a light-proof property or the like, a lens body can be disposed at the lower end of a disposable tip or a tip of a cleaning system such that it focuses light at a point where the change of the amount of received light can be checked with high precision. For instance said point could be located at an internal opening section at the lower end of a disposable tip or at a position slightly lower than a lower edge of the disposable tip. In this case, a liquid level can be detected with high precision without any noise therein.
In the present invention, light is supplied to a liquid contained in a vessel by transmitting it continuously through a nozzle or blinking it in a flashes therethrough or by means of optical filters, or is supplied from the outside of the nozzle.
Data obtained by the method for sucking/determinin; the level of a liquid having the ~9 Doc. No 76-4 CA PCT f'atcnt construction as described above are used as data for controlling a pipetting device in which driving required for pipetting a liquid to cylinders for moving the nozzle upward/downward as well as for sucking/discharginl; the level of a liquid is controlled, which makes it possible to realize a high precision control.
INDUSTRIAL APPLICAFtILITY
As described above, the method for slICklIlg/detel'Illlnlng the level of a liduid according to the present invention amd a pipetting device driven and controlled according to the method are applicable for use in procedures such as qualifying, quantifying, separating.
and pipetting a specimen or a sample, identifying a liquid level, and checking whether contents of pipetting are satisfied or not in a clinical inspection. In addition, it is applicable to procedures such as qualifying, quantifying, separating, anti pipetting a used drug.
identifying a liquid level, and checking whether contents of pipetting are satisfied or not in a chemical analysis, to procedures such as qualifying, quantifying, separating, and pipetting a specimen or a sample, identifying a liquid level, and checking whether contents of pipetting are satisfied or not in a DNA analysis, to procedures such tls qualifying.
quantifying, separating, and pipetting a used drug, identifying a liquid level, and checkin'=
whether contents of pipetting are satisfied or not in a system of producing drugs. to procedures such as qualifying, quantifying, separating, and pipetting a specimen or a sample, identifying a liquid level, and checking whether contents of pipetting are satisfied or not in a bacteria and virus inspection, to procedures such as qualifying, quantifyin~l.
separating, and pipetting a specimc°n or a sample. identifying a liquid level, and checking whether contents of pipetting are satisfied or not in a water quality inspection, and furthermore to procedures such as qualifying, quantifying. separating. and pipetting a used drug, identifying a liquid level, and checking whether contents of pipetting are satisfied or not each in color synthesis.
Claims (31)
1. A method for sucking/determining the level of a liquid contained in a vessel by means of a nozzle, comprising the steps of:
positioning a light receiver inside the nozzle; and receiving light irradiation proceeding from the liquid at or near an opening located at a lower end of a disposable tip or a tip of a cleaning system attached to the lower end of said nozzle through a space defined by the said disposable tip or the tip of the cleaning system and entering into the lower end of said nozzle, and detecting fluctuation of said received light irradiation.
positioning a light receiver inside the nozzle; and receiving light irradiation proceeding from the liquid at or near an opening located at a lower end of a disposable tip or a tip of a cleaning system attached to the lower end of said nozzle through a space defined by the said disposable tip or the tip of the cleaning system and entering into the lower end of said nozzle, and detecting fluctuation of said received light irradiation.
2. A method according to claim 1, wherein said light irradiation from the liquid at or near the opening located at the lover end of the disposable tip or the tip of the cleaning system in the receiving step of claim 1, is generated by light irradiated from a light source located at the nozzle to the liquid at or near the opening located at the lower end of the disposable tip or the tip of the cleaning system.
3. A method according to claim 1, wherein said light irradiation from the liquid at or near the opening located at the lower end of the disposable tip or the tip of the cleaning system in the receiving step of claim 1, is generated by light irradiated from a light source located outside of said nozzle to the liquid at or near the opening located at the lower end of the disposable tip or the tip of the cleaning system.
4. A method according to claim 1 or claim 2, further comprising the step of positioning said light receiver in a lower edge section of the nozzle.
5. A method according to claim 1 or claim 2, further comprising the step of providing a focusing lens at a position lower than a lower edge section of the light receiver.
6. A method according to claim 2, further comprising the step of providing a focusing lens at a position lower than an edge section of the light source.
7. A method according to claim 1, further comprising the step of positioning said light receiver at a center of the nozzle.
8. A method for sucking/determining the level of a liquid contained in a vessel by means of a nozzle, comprising the steps of:
providing a light receiver; and receiving light irradiation proceeding from the liquid at or near an opening located at a lower end of a disposable tip or a tip of a cleaning system attached to the lower end of said nozzle through a space defined by said disposable tip or the tip of the cleaning system and entering into the lower end of said nozzle, and detecting fluctuation of said received light irradiation, wherein the light receiver is not positioned exteriorly of the disposable tip or on an outer side of the nozzle.
providing a light receiver; and receiving light irradiation proceeding from the liquid at or near an opening located at a lower end of a disposable tip or a tip of a cleaning system attached to the lower end of said nozzle through a space defined by said disposable tip or the tip of the cleaning system and entering into the lower end of said nozzle, and detecting fluctuation of said received light irradiation, wherein the light receiver is not positioned exteriorly of the disposable tip or on an outer side of the nozzle.
9. A method according to claim 8, further comprising the steps of filling said disposable tip or said tip of a cleaning system attached to said nozzle with the liquid, and receiving light by said nozzle through said liquid in said disposable tip or said tip of a cleaning system
10. A method according to claim 9, further comprising the steps of determining a sucking rate of a liquid, its transparency, presence of bubbles therein, and a clogged state or a dry state of the tip by detecting fluctuation of the amount of the received light by the sucked liquid.
11. A method according to claim 9, wherein the step of filling said disposable tip or said tip of a cleaning system attached to said nozzle with the liquid, and receiving light by said nozzle through said liquid in said disposable tip or said tip of a cleaning system further includes recognizing a change of color with the nozzle, by detecting a change in wavelength.
12. A method according to claim 9, wherein the step of filling said disposable tip or said tip of a cleaning system attached to said nozzle with the liquid, and receiving light by said nozzle through said liquid in said disposable tip or said tip of a cleaning system further includes detecting the color of a colored vessel containing said liquid therein.
13. A method according to claim 9, wherein the step of filling said disposable tip or said tip of a cleaning system attached to said nozzle with the liquid, and receiving light by said nozzle through said liquid in said disposable tip or said tip of a cleaning system further includes detecting, through the liquid, the color of a rack or a holder, in which a transparent vessel containing the liquid therein is provided in an upright state.
14. A method according to claim 9, wherein the step of filling said disposable tip or said tip of a cleaning system attached to said nozzle with the liquid, and receiving light by said nozzle through said liquid in said disposable tip or said tip of a cleaning system further includes detecting an interface with a solid surface or a liquid surface contacting a bottom surface of the sucked liquid by determining a change in the amount or wavelength of the received light when said disposable tip sucks the liquid.
15. A method according to claim 2, further comprising the step of passing the light through a transparent disposable tip or a transparent tip of a cleaning system connected to said nozzle.
16. A method according to claim 2, further comprising the step of irradiating light when the nozzle is brought close to a surface of the liquid in a container while sucking the liquid
17. A method according to claim 2, further comprising the step of irradiating light through the opening at the lower end of the disposable tip or the tip of the cleaning system attached to the lower end of said nozzle when bringing the disposable tip or the tip of the cleaning system close to the surface of a liquid accommodated in a vessel.
18. A pipette device, in which the driving force required for pipetting a liquid to a cylinder, for changing tile relative position between said cylinder and said nozzle upward/downward, and for sucking/discharging a liquid is controlled, comprising:
a nozzle having an opening section located at a lower end thereof;
a disposable tip or a tip of a cleaning system having a first, upper end attached to the lower end of said nozzle and having; a second, lower end adapted to suck liquid thereinto;
a light receiver positioned inside the nozzle for receiving light proceeding from the liquid at or near the opening of said lower end of said disposable tip or said tip of a cleaning system and entering into the opening section of said nozzle; and a light detector for detecting fluctuations of said received light.
a nozzle having an opening section located at a lower end thereof;
a disposable tip or a tip of a cleaning system having a first, upper end attached to the lower end of said nozzle and having; a second, lower end adapted to suck liquid thereinto;
a light receiver positioned inside the nozzle for receiving light proceeding from the liquid at or near the opening of said lower end of said disposable tip or said tip of a cleaning system and entering into the opening section of said nozzle; and a light detector for detecting fluctuations of said received light.
19. A pipette device according to claim 18, further comprising a light source for irradiating light at said opening section of said nozzle and through an opening at said lower end of said disposable tip or said tip of the cleaning system when bringing said disposable tip or said tip or said tip of the cleaning system close to the surface of the liquid contained in a vessel.
20. A pipette device according to claim 18 or claim 19, wherein said light receiver is positioned in a lower edge section of the nozzle.
21. A pipette device according to claim 18 or 19, further comprising a focusing lens at a position lower than a lower edge section of the light receiver.
22. A pipette device according to claim 19, further comprising a focusing lens at a position lower than a lower edge section of the light source.
23. A pipette device according to claim 18 or claim 19, wherein at least one optical fiber is provided in said nozzle.
24. A pipette device according to claim 18 or claim 19, further comprising an optical fiber provided in said nozzle, through which at least one of irradiation, transmission, and reception of light to and from said liquid is performed.
25. A pipette device according to claim 24, wherein a light receiving edge section of said at least one optical fiber, is provided in a bottom edge or a side portion of said nozzle.
26. A pipette device according to claim 19, wherein the disposable tip or the tip of a cleaning system is transparent.
27. A pipette device according to claim 18 or claim 19, wherein the disposable tip or tip of a cleaning system is subjected to a light-proof processing.
28. A pipetting device according to claim 27, wherein said light-proof processing is a coloring processing.
29. A pipetting device according to claim 18, wherein said nozzle is formed in a tubular form with a light transmitting material.
30. A pipetting device according to claim 18, wherein at least a lower edge section of said nozzle is formed with a light transmitting material.
31. A pipetting device according to claim 18 or claim 19, wherein said nozzle is subjected to a light-proof processing.
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP7-109157 | 1995-04-11 | ||
| JP10915795 | 1995-04-11 | ||
| JP8-111901 | 1996-04-09 | ||
| JP11190196 | 1996-04-09 | ||
| PCT/JP1996/000993 WO1996032649A1 (en) | 1995-04-11 | 1996-04-11 | Liquid suction examination method and dispensation apparatus driving-controlled by the same |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2183639A1 CA2183639A1 (en) | 1996-10-12 |
| CA2183639C true CA2183639C (en) | 2001-06-12 |
Family
ID=26448944
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002183639A Expired - Fee Related CA2183639C (en) | 1995-04-11 | 1996-04-11 | Method for sucking/determining liquid and pipetting device driven and controlled according to method |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA2183639C (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3567359B1 (en) * | 2018-05-08 | 2022-10-05 | Sartorius Biohit Liquid Handling Oy | Liquid handling system and a method for analysing a state of a tip |
-
1996
- 1996-04-11 CA CA002183639A patent/CA2183639C/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CA2183639A1 (en) | 1996-10-12 |
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