Patent Publication Number: US-8117927-B2

Title: Pipette providing sampling via back-and-forth movement of the piston

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is a continuation application of International Application No. PCT/EP2008/058090 filed on Jun. 25, 2008, the entire contents of which is hereby incorporated by reference; which claims priority under the Paris Convention to French Patent Application No. 0756008, filed Jun. 25, 2007, the disclosure of which is incorporated by reference herein in its entirety. 
    
    
     BACKGROUND 
     Sampling pipettes are known from the prior art having a conventional design of the type integrating an upper pipette body forming a handle, and a lower pipette body having at its lower end one or more tip holding nozzles, whose function is to hold sampling tips, also called consumables. The lower pipette body houses a sliding piston controlled by manual or motorized equipment causing the piston to move upward during liquid sampling phases and to move downward during liquid transfer phases. The upward movement is generally performed under the effect of release of a spring that is compressed during the previous downward movement. This type of design is found both in single channel pipettes, having a single tip holding nozzle, and in multichannel pipettes, having a plurality of tip holding nozzles, whether the pipette is manual or motorized. 
     The upward stroke imposed upon the piston determines the volume of sampled liquid, a volume which is previously set by the user using a variety of possible controls including a thumb wheel, an adjusting screw, a digital keypad, etc. 
     On conventional pipettes, the piston is of strictly cylindrical shape and slides within a cavity of complementary shape, made in the lower body of the pipette and delimiting an aspiration chamber. The aspiration chamber is partly delimited by the lower end of the piston, which means that its volume varies when the piston is moved. Therefore, the volume of sampled liquid, corresponding to the increase in air volume in the aspiration chamber subsequent to a given stroke of the piston, is substantially equal to the product of the cross-section of the piston by the length of the given stroke of the piston. 
     Consequently, the sampling capacity of a pipette is determined at the present time both by the cross-section of the piston and by the length of the maximum stroke. Therefore, to increase pipette capacity in terms of the maximum value of liquid volume the pipette can sample or the ratio between the maximum and minimum values the liquid volume pipette can sample, typically in the order of 10 to 20, it is necessary to increase the value of at least one of the cross-section of the piston and/or the length of the piston stroke. Relative to the maximum stroke length, any increase in length rapidly leads to problems of global ergonomics for the pipette. Relative to the cross-section of the piston, i.e. the piston diameter, any increase thereof generally has a detrimental effect on the accuracy and repeatability of the sampled volume. The design of conventional pipettes does not therefore allow the simultaneous combining of essential criteria such as a large sampling capacity, ergonomics, accuracy, and repeatability of sampled volumes. 
     Multi-volume pipettes include a succession of chambers of increasing diameters/volumes starting from the tip holder, each one cooperating with a piston section of corresponding diameter. The placing or non-placing in communication of these chambers, isolated from each other, allows the pipette to be adapted to the value of the liquid volume to be sampled. Nevertheless, multi-volume pipettes do not solve the problems in a fully satisfactory manner because the more the capacity of the pipette is increased, the greater the number of aspiration chambers that are superimposed in the direction of the piston&#39;s sliding movement. The increase in the number of chambers leads to an increase in the total length of the pipette which is detrimental to the pipette&#39;s ergonomics. Also, the greater the volume of liquid to be sampled, the less accuracy and repeatable the pipette becomes due to the chamber and piston having a greater diameter. 
     SUMMARY 
     In an example embodiment, a pipette is provided. The device includes, but is not limited to, a body, a piston, and a valve. The body includes a nozzle, a first chamber, a second chamber, and a channel formed in the nozzle. The first chamber is isolated from the second chamber, and the channel is isolated from the first chamber and the second chamber. The piston is mounted to slide within the first chamber and the second chamber so that movement of the piston simultaneously increases a first volume of the first chamber and decreases a second volume of the second chamber. The valve is in communication with the first chamber, the second chamber, the channel, and an exterior of the body to selectively provide a communication between the first chamber and the channel, between the second chamber and the channel, between the first chamber and the exterior of the body, and between the second chamber and the exterior of the body. 
     In another example embodiment, a computer-readable medium is provided having stored thereon computer-readable instructions that, when executed by a processor, cause a device to: 
     (a) switch a valve to provide communication between a first chamber and an exterior of a body of the device wherein the body houses a nozzle, the first chamber, a second chamber, a channel formed in the nozzle, and a piston mounted to slide within the first chamber and the second chamber; 
     (b) switch the valve to provide communication between the second chamber and the channel, wherein the second chamber and the channel are isolated from the first chamber; 
     (c) slide the piston in a first direction decreasing a first volume of the first chamber and increasing a second volume of the second chamber thereby aspirating a first volume of liquid into a tip of the device; 
     (d) switch the valve to provide communication between the first chamber and the channel; 
     (e) switch the valve to provide communication between the second chamber and the exterior of the body; 
     (f) slide the piston in a second direction opposite the first direction increasing the first volume of the first chamber and decreasing the second volume of the second chamber thereby aspirating a second volume of liquid into the tip of the device; and 
     (g) repeat (a)-(f) until a selected volume is aspirated into the tip of the device. 
     Other principal features and advantages of the invention will become apparent to those skilled in the art upon review of the following drawings, the detailed description, and the appended claims. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       Example embodiments of the invention will hereafter be described with reference to the accompanying drawings, wherein like numerals denote like elements. 
         FIG. 1  is a perspective view of a sampling pipette in accordance with an example embodiment. 
         FIG. 2  is a block diagram of a sampling pipette in accordance with an example embodiment. 
         FIG. 3  depicts a partial, cross-sectional, side view of a sampling pipette in accordance with a first example embodiment. 
         FIGS. 4   a  to  4   d  depict partial, cross-sectional, side views of the sampling pipette of  FIG. 3  illustrating use of the sampling pipette. 
         FIG. 5  depicts a partial, cross-sectional, side view of a sampling pipette in accordance with a second example embodiment. 
         FIG. 6  depicts a partial, cross-sectional, side view of a sampling pipette in accordance with a third example embodiment. 
         FIG. 7  depicts a partial, cross-sectional, side view of a sampling pipette in accordance with a fourth example embodiment. 
         FIGS. 8   a  and  8   b  depict partial, cross-sectional, side views of a sampling pipette in accordance with a fifth example embodiment. 
         FIGS. 9   a  and  9   b  depict partially exploded cross-sectional, side views of the sampling pipette of  FIGS. 8   a  and  8   b , respectively. 
     
    
    
     DETAILED DESCRIPTION 
     With reference to  FIG. 1 , a sampling pipette  100  is shown in accordance with an example embodiment. Sampling pipette  100  can be controlled to manually or electronically aspirate and dispense liquid volumes into a sampling tip  30 . In the example embodiment of  FIG. 1 , sampling pipette  100  is hand-held. In alternative embodiments, the sampling pipette may include a multichannel pipette and/or the sampling pipette may not be hand-held. Sampling pipette  100  includes a number of components and subsystems that together provide various operational modes for aspirating and dispensing liquids in specified volumes. With reference to  FIG. 1 , the external components and subsystems of sampling pipette  100  may include, but are not limited to, a body case  104 , a nozzle  3 , a tip ejector  108 , a display  118 , and a plurality of user controls  120 . Some of these components and subsystems are known to those skilled in the art, and thus, will not be discussed in significant detail herein. 
     In the example embodiment of  FIG. 1 , body case  104  provides a comfortable external cover for a user holding sampling pipette  100  and protects the components of sampling pipette  100 . Body case  104  includes, but is not limited to, a front case  110 , a rear case  112 , and a finger rest  114 . Front case  110  mounts to rear case  112  to enclose a piston drive mechanism, a piston, and control electronics. Finger rest  114  mounts to rear case  112  and provides a bracing point, for example, for the pipette user&#39;s index finger to rest against while holding the body of sampling pipette  100  in the palm of the hand. As used herein, the term “mount” includes join, unite, connect, associate, insert, hang, hold, affix, attach, fasten, bind, paste, secure, bolt, screw, rivet, solder, weld, press against, formed with, glue, and other like terms. 
     Nozzle  3  mounts to body case  104 . In the example embodiment of  FIG. 1 , a nut  116  slides over an end of front case  110  and an end of rear case  112  to mount front case  110  to rear case  112  and nozzle  3  to body case  104 . Nut  116  thus allows removable mounting of the external body components to each other. 
     With reference to  FIG. 2 , a block diagram of internal components of sampling pipette  100  is shown in accordance with an example embodiment. Sampling pipette  100  may further include an output interface  200 , an input interface  202 , a computer-readable medium  204 , a processor  206 , a control application  208 , a motor  210 , a piston drive mechanism  212 , a piston  12 , and one or more valves  42 ,  44 . In another example embodiment, one or more of the components of sampling pipette  100  may be located at a distance from the other components and connected through either wired or wireless communication technologies. 
     Output interface  200  provides an interface for outputting information for review by a user of sampling pipette  100 . For example, output interface  200  may include an interface to display  118 . Display  118  may be a thin film transistor display, a light emitting diode display, a liquid crystal display, or any of a variety of different displays known to those skilled in the art. Sampling pipette  100  may have one or more output interfaces that use the same or a different interface technology. 
     Input interface  202  provides an interface for receiving information from the user for entry into sampling pipette  100  as known to those skilled in the art. Input interface  202  may use various input technologies including, but not limited to, a keyboard, a pen and touch screen, a mouse, a track ball, a touch screen, a keypad, one or more buttons, etc. to allow the user to enter information into sampling pipette  100  or to make selections presented in a user interface displayed on display  118 . Input interface  202  may provide both an input and an output interface. For example, a touch screen both allows user input and presents output to the user. Sampling pipette  100  may have one or more input interfaces that use the same or a different input interface technology. For example, sampling pipette  100  may include the plurality of user controls  120  that can be used by an operator of sampling pipette  100  to control the operating characteristics of sampling pipette  100 . The plurality of user controls  120  may include a thumbwheel, buttons, adjustment screws, a digital keypad, etc. 
     Computer-readable medium  204  is an electronic holding place or storage for information so that the information can be accessed by processor  206  as known to those skilled in the art. Computer-readable medium  204  can include, but is not limited to, any type of random access memory (RAM), any type of read only memory (ROM), any type of flash memory, etc. such as magnetic storage devices (e.g., hard disk, floppy disk, magnetic strips, . . . ), optical disks (e.g., CD, DVD, . . . ), smart cards, flash memory devices, etc. Sampling pipette  100  may have one or more computer-readable media that use the same or a different memory media technology. Sampling pipette  100  also may have one or more drives that support the loading of a memory media such as a CD or DVD. 
     Processor  206  executes instructions as known to those skilled in the art. The instructions may be carried out by a special purpose computer, logic circuits, or hardware circuits. Thus, processor  206  may be implemented in hardware or firmware, or any combination of these methods. The term “execution” is the process of running an application or the carrying out of the operation called for by an instruction. The instructions may be written using one or more programming language, scripting language, assembly language, etc. Processor  206  executes an instruction, meaning that it performs the operations called for by that instruction. Processor  206  operably couples with output interface  200 , with input interface  202 , with computer-readable medium  204 , with motor  210 , and with the one or more valves  42 ,  44  to receive, to send, and to process information. Processor  206  may retrieve a set of instructions from a permanent memory device and copy the instructions in an executable form to a temporary memory device that is generally some form of RAM. Sampling pipette  100  may include a plurality of processors that use the same or a different processing technology. 
     Control application  208  performs operations associated with control of sampling pipette  100 . Control application  208  may receive input through input interface  202 . Control application  208  may be written using one or more programming languages, assembly languages, scripting languages, etc. 
     Piston drive mechanism  212  causes the aspiration and dispensation of a specified volume of liquid into and out of sampling tip  30  by moving piston  12  within a chamber housed in body case  104  along a longitudinal axis that extends along the body of sampling pipette  100 . Motion of piston  12  produces an air displacement that aspirates or dispenses liquid into or out of sampling tip  30 . Piston drive mechanism  212  may be manually positioned and moved by a user. In an alternative embodiment, piston drive mechanism  212  may be positioned and moved by motor  210 . 
     Motor  210  may position piston drive mechanism  212  and move piston  12  under the control of processor  206  and control application  208 . Motor  210  may be implemented using a variety of electromechanical devices as known to those skilled in the art. Motor  210  through piston drive mechanism  212  precisely moves piston  12  up and down the longitudinal axis of sampling pipette  100  to aspirate or to dispense liquid into or out of sampling tip  30 . 
     With reference to  FIG. 3 , a portion of sampling pipette  100  is shown in accordance with a first example embodiment. In the description, the indications “top”/“upper”/“bottom”/“lower” are to be considered with respect to a longitudinal axis  5  of the pipette when it is held in an operator&#39;s hand for a pipetting operation or mounted to perform a pipetting operation. Nozzle  3  may have a variety of shapes and sizes and may include one or more sections. In the example embodiment of  FIG. 3 , nozzle  3  includes a lower pipette body  4  which may comprise at the lower end a tip holding nozzle  6  of conventional flattened cone shape. Lower pipette body  4  is hollow so that it can house piston  12  mounted to slide in an appropriate cavity. 
     Piston  12  is housed in the cavity and has an upper cylindrical portion  12   a  and a lower cylindrical portion  12   b  of larger diameter, each of the portions  12   a ,  12   b  respectively being guided by a section of the lower body  4   a ,  4   b  of complementary shape. Additionally, each of the two sections  4   a ,  4   b  respectively is hollow and has a fixed seal. The seals follow the contour of piston  12  which slides with respect thereto. 
     With reference to the example embodiment of  FIG. 3 , a lower aspiration chamber  20  is delimited by a lower seal  14 , a lower end  24  of piston  12 , an inner wall of section  4   b , and a lower wall  26  made in lower pipette body  4 . Lower wall  26  isolates chamber  20  from a nozzle through channel  28  made at least in part along axis  5  in tip holding nozzle  6  so that it can communicate with sampling tip  30  when it is fitted onto tip holding nozzle  6 . More precisely, channel  28  leads downwards into sampling tip  30  and, in its more upper part, has a branch point so that it can open into its other end radially/laterally relative to lower pipette body  4 , enabling it to communicate with valve  42 . 
     An upper aspiration chamber  22  is delimited by an upper seal  16 , an upper piston portion  12   a , an inner wall of section  4   b , an upper end  32  of the lower piston portion  12   b , and a seal  14 . Seal  14  assists in isolating the two aspiration chambers  20 ,  22 . The upper aspiration chamber  22  is additionally isolated from nozzle through channel  28 . 
     With this arrangement in which piston portions  12   a ,  12   b  respectively follow the contour of the inner wall of section  4   a  and the inner wall of section  4   b , the chamber  20  has a constant cross section relative to axis  5 , in the form of a disc having the same axis and a diameter equal to the diameter of the inner wall of section  4   b . Chamber  22  has a constant cross section relative to axis  5 , in the shape of an annular ring of the same axis having an outer diameter equal to the inner wall of section  4   b , and an inner diameter equal to the outer diameter of the upper piston portion  12   a.    
     Piston  12  is moved to slide up or down parallel to longitudinal axis  5  relative to lower pipette body  4 . In the remainder of the description, the direction of upward sliding  36  is termed an “upward stroke” of piston  12  while the direction of downward sliding  38  is termed a “downward stroke” of piston  12 . Therefore, an upward stroke of piston  12  simultaneously causes an increase in the volume of the lower chamber  20  and a decrease in the volume of the upper chamber  22 , while conversely a downward stroke of piston  12  simultaneously causes an increase in the volume of the upper chamber  22  and a decrease in the volume of the lower chamber  20 . In another example embodiment, the effects described above can be reversed with a different design of the chamber  20 ,  22 . 
     The pipette  100  also comprises fluid communication implementation means  40  comprising two three-way solenoid valves  42 ,  44  of known type, which will not be further described. However, by way of indication, three-way solenoid valves  42 ,  44  may be linear piston solenoid valves having three inlets  1 ,  2 ,  3  which, via the movement of piston  12 , alternately support communication between inlets  1  and  2  and between inlets  1  and  3 . Example three-way solenoid valves  42 ,  44  may be those marketed by LEE COMPANY under reference LHDA 053 1115H. 
     The fluid communication implementation means  40 , when appropriately controlled, they allow liquid to be sampled both during the upward stroke of the piston  12  and during its downward stroke, so that liquid can be drawn into the sampling tip  30  continuously during a back-and-forth (up and down) movement of the piston  12 . Using this mechanism, the only limitation on the maximum volume which can be sampled is therefore the capacity of the sampling tip  30  and no longer the design of the pipette as was the case with prior art embodiments. Additionally, subsequent dispensing of the liquid into another receptacle is similarly performed i.e. via a back-and-forth (up and down) movement of the piston  12 , which may if necessary comprise several return strokes. 
     The first three-way solenoid valve  42  is mounted to alternately place in communication one of the two chambers  20 ,  22  with the nozzle through channel  28 , while the second three-way solenoid valve  44  is mounted to alternately place in communication one of the two chambers  20 ,  22  with the exterior of body case  104  of pipette  100 . The valves  42 ,  44  are synchronized and controlled automatically by processor  206  under control of control application  208  to which valves  42 ,  44  are electrically connected. 
     Therefore, the first solenoid valve  42  has three inlets  1 , 2 , 3  of which inlet  1  communicates with the nozzle through channel  28  at its upper end opening radially/laterally into the body  4 , inlet  2  communicates with the lower chamber  20  via a first channel connected through the wall of section  4   b , and inlet  3  communicates with the upper chamber  22  via a second channel connected through the wall of section  4   b . The above-indicated communications may be permanently established by connecting conduits or by channels directly made in pipette body  4 . The inlets only communicate with each other when the first solenoid valve  42  is controlled for this purpose. In the example embodiment, only communications between inlets  1  and  2  and between inlets  1  and  3  may be alternately provided by the sliding valve piston. Communication between inlets  2  and  3  may not implemented and may be made impossible by the design of the solenoid valve. 
     Similarly, the second solenoid valve  44  has three inlets  1 ,  2 ,  3  of which inlet  1  communicates with the upper chamber  22  via a third channel connected through the wall of section  4   b , inlet  2  communicates with the lower chamber  20  via a fourth channel connected through the wall of section  4   b , and inlet  3  communicates with the ambient air exterior of body case  104  of pipette  100 . The communications may be established permanently e.g. via simple connecting conduits. The inlets may only communicate with each other when the second solenoid valve  44  is controlled for this purpose. In the example embodiment, only communications between inlets  1  and  2  and between inlets  1  and  3  may be alternately provided by the sliding valve piston. Communication between inlets  2  and  3  may not implemented and may be made impossible by the design of the solenoid valve. 
     Therefore, with reference to  FIG. 3 , when inlets  1  and  2  of first solenoid valve  42  are in communication, a first fluid communication referenced A provides a free circulation of air between the lower chamber  20  and the nozzle channel  28  leading into the tip  30 , but prevents communication of nozzle channel  28  with chamber  22 . Also, when inlets  1  and  3  of first solenoid valve  42  are in communication, they ensure a second fluid communication referenced B, which provides free circulation of air between the upper chamber  22  and the nozzle channel  28  leading into the tip  30 , but prevents communication of nozzle channel  28  with chamber  20 . 
     Similarly, the second solenoid valve  44 , when inlets  1  and  3  are in communication, ensures a third fluid communication referenced C, which provides free circulation of air between the upper chamber  22  and the exterior of body case  104  of pipette  100 , but prevents communication between the exterior and chamber  20 . Also, when inlets  2  and  3  are in communication, they ensure a fourth fluid communication referenced D, which provides free circulation of air between the lower chamber  20  and the exterior of the pipette, but in this case prevents communication between the exterior and chamber  22 . 
     With reference to  FIGS. 4   a  to  4   d , the operation of sampling pipette  100  is illustrated. First, the pipette user enters the value of the volume to be sampled using for example, the plurality of user controls  120 . The entered value may be displayed on display  118  and transmitted to a processor  206  executing control application  208 . 
     Control application  208  determines the number of piston strokes and their length in relation to the volume to be sampled. For example, if the desired value is 400 microliters (μl), and each maximum upward and downward stroke allows a quantity of 100 μl to be sampled, control application  208  determines that two return strokes of the piston  12  are made with maximum stroke lengths each ensuring the sampling of 100 μl. Because in the example embodiment of  FIG. 3 , the two chambers  20 ,  22  have different cross sections, to obtain the same sampling or the same dispensing of liquid in both stroke directions, one of the two strokes lengths may be set at a higher value than the other. 
     The above data, once determined, can optionally be displayed on display  118  for visualization by the user who may initiate pipetting for example by pressing a button of the plurality of user controls  120  provided for this purpose, after dipping the tip  30  in the recipient of liquid to be sampled. 
     Control application  208  may deliver instructions to the solenoid valves  42 ,  44  so that they switch over to a configuration setting up communications A and C if not already established. Control application  208  may deliver instructions to motor  210  to place the piston in upward movement  36  which upward movement may be obtained by mere releasing of a spring compressed during a preceding downward phase of the piston  12 . During this movement, the volume of chamber  20  increases which sets up aspiration in communication A in the direction leading from the channel  28  towards chamber  20 , since communication C isolates this chamber from the exterior air. This aspiration translates as rising of the liquid in the sampling tip  30  whose distal end is immersed in this same liquid. At the same time, communication C allows air to escape from the upper chamber  22  whose volume decreases, the air escaping to exterior the pipette prevents the onset of over-pressure in chamber  22 . 
     At the end of the first upward stroke of the piston shown in  FIG. 4   a , the quantity of liquid drawn into the tip is therefore 100 μl. Control application  208  delivers instructions to solenoid valves  42 ,  44  so that they simultaneously switch over to a configuration setting up communications B and D. Control application  208  delivers instructions to motor  210  to place the piston in movement in the downward direction  38 . During this movement shown in  FIG. 4   b , the volume of chamber  22  increases, which sets up aspiration in communication B in the direction leading from the channel  28  towards the chamber  22 , since communication D isolates this chamber from the exterior air. This aspiration translates as a new rise of liquid in the tip  30  whose distal end is still immersed in this same liquid. At the same time, communication D allows air to escape from the lower chamber  20  whose volume decreases, the air escaping to exterior the pipette which prevents the onset of over pressure in chamber  20 . Therefore, the upward and downward strokes of the piston  12  follow each other alternately as many times as is necessary i.e. four times in this case to reach the desired volume of 400 μl. Control application  208  may provide an indication in display  118  of the number of strokes already conducted and/or remaining to be conducted. 
     When the second and last back-and-forth movement of the piston is completed, the desired volume of 400 μl contained in the sampling tip  30  can be dispensed/transferred to another receptacle in a similar manner. Here again, the display  118  may automatically display the number of strokes to be performed to ensure full dispensing of the desired volume, and can display the number of strokes already performed and/or remaining to be performed for this dispensing operation. 
     Once the tip  30  is inserted in the receptacle intended to collect the previously aspirated liquid, the user can provide the instruction for example by pressing a button of the plurality of user controls  120  provided for this purpose, to initiate dispensing of the liquid. At the time dispensing is initiated, the piston  12  lies in bottom position with solenoid valves  42 ,  44  setting up communications B and D. Control application  208  delivers an instruction to place the piston  12  in movement in the upward direction  36 . During this movement illustrated in  FIG. 4   c , the volume of the upper chamber  22  is decreases, which sets up a pressure in communication B leading from chamber  22  towards channel  28 , since communication D isolates this chamber  22  from exterior air. This pressure translates as ejection of the liquid through the distal end of the tip  30  into the appropriate receptacle. At the same time, communication D allows exterior air to enter into the lower chamber  20  whose volume is increased, thereby preventing the onset of negative pressure in chamber  20 . 
     At the end of the first upward stroke of the piston, the quantity of liquid extracted from the tip is therefore 100 μl. Control application  208  delivers instructions to the solenoid valves  42 ,  44  so that they switch over to a configuration setting up communications A and C. Control application  208  delivers instructions to motor  210  to place the piston  12  in movement in the downward direction  38 . During this movement illustrate in  FIG. 4   d , the volume of the lower chamber  20  is seen to decrease which sets up pressure inside communication A in the direction leading from chamber  20  towards nozzle channel  28 , since communication C isolates chamber  20  from the exterior air. This pressure translates as a new ejection of liquid through the distal end of the tip  30  into the appropriate receptacle. At the same time, communication C allows exterior air to enter the upper chamber  22  whose volume is increased, thereby preventing the onset of a negative pressure in chamber  22 . Therefore, the upward and downward strokes of the piston  12  follow after each other alternately as many times as is necessary i.e. four times in this case to transfer the desired volume of 400 μl. 
     With reference to  FIG. 5 , a portion of sampling pipette  100  is shown in accordance with a second example embodiment. Only the connections of the first and second solenoid valves  42 ,  44  have been modified with respect to those previously described. The first solenoid valve  42  has three inlets  1 ,  2 ,  3  of which inlet  1  communicates with the nozzle channel  28 , at its upper end opening radially/laterally into the body  4 , inlet  2  communicates with the lower chamber  20  via section  4   b , and inlet  3  communicates with the exterior of the pipette. The communications may be permanently established for example using simple connecting conduits. The inlets only communicate with each other when the solenoid valve  42  is controlled for this purpose. In the example embodiment, only communications between inlets  1  and  2  and between inlets  1  and  3  may be alternately provided by the sliding valve piston. Communication between inlets  2  and  3  may not implemented and may be made impossible by the design of the solenoid valve. 
     The second solenoid valve  44  has three inlets  1 ,  2   3 , of which inlet  2  communicates with the nozzle channel  28  at another upper end opening radially/laterally into the body  4 , inlet  1  communicates with chamber  22  via section  4   b  and inlet  3  communicates with the exterior of the pipette. The communications may be permanently established for example using simple connecting conduits. The inlets only communicate with each other when the second solenoid valve  44  is controlled for this purpose. In the example embodiment, only communications between inlets  1  and  2  and between inlets  1  and  3  may be alternately provided by the sliding valve piston. Communication between inlets  2  and  3  may not implemented and may be made impossible by the design of the solenoid valve. 
     With reference to  FIG. 5 , the first solenoid valve  42 , when inlets  1  and  2  are in communication, ensures the first fluid communication A which provides free circulation of air between the lower chamber  20  and the nozzle channel  28  leading into the tip  30 , while preventing communication of this chamber  20  with the exterior. When inlets  2  and  3  are in communication, the first solenoid valve  42  ensures the fourth fluid communication D allowing free circulation of air between the lower chamber  20  and the exterior of the pipette, but in this case preventing communication of channel  28  with chamber  20 . Thus, second solenoid valve  42  is particularly dedicated to the management of air in the lower chamber  20  and does not communicate with the upper chamber  22 . 
     Similarly, it can be seen with reference to  FIG. 5  that the second solenoid valve  44 , when inlets  1  and  2  are in communication, ensures the second fluid communication B which provides the free circulation of air between chamber  22  and the nozzle channel  28  leading into the tip  30 , while preventing communication between this chamber  22  and the exterior. On the other hand, when inlets  1  and  3  are in communication, second solenoid valve  44  ensures the third fluid communication C which provides the free circulation of air between the upper chamber  22  and the exterior of the pipette, but prevents communication of channel  28  with this chamber  22 . Thus, the second solenoid valve  44  is particularly dedicated to the management of air in the upper chamber  22  without communicating with the lower chamber  20 . 
     The second embodiment of  FIG. 5  reduces the risk of liquid leakage to zero, even if the synchronization of the two solenoid valves is not perfect. For example, subsequent to an upward stroke of the piston  12  leading to liquid sampling through the establishment of communications A and C, switching of the first solenoid valve  42  over to configuration D carried out slightly before second solenoid valve  44  switches over to configuration B, does not involve any break in the negative pressure prevailing in channel  28  and the tip  30  filled with liquid because the volume inside these latter parts becomes sealed and therefore does not communicate with the exterior. The same applies to the reverse case when switching of second solenoid valve  44  is made slightly before the switching of first solenoid valve  42 , since the volume of air in the nozzle channel  28  and tip  30  are first placed in communication with chamber  22  which has become isolated from the exterior by means of fluid communication B. Here again, the lack of any break in the negative pressure prevailing in channel  28  and the tip  30  prevents the leakage of liquid already sampled and contained in the tip  30 . 
     This beneficial effect applies both when the stroke direction is reversed with the piston lying in a top position, and when the stroke direction is reversed with the piston lying in a bottom position. The pipette fabricated in this manner is therefore able to offer very high accuracy since, irrespective of the order of switching of the solenoid valves instructed by the processor  206  before each inversion of the piston stroke, there is no risk of any liquid leakage. Relative to the embodiment illustrated in  FIG. 5 , the control application  208  is programmed so that the functioning of the pipette is as described above, in particular regarding the automatic, alternate establishing of fluid communications A and C and fluid communications B and D. 
     With reference to  FIG. 6 , a portion of sampling pipette  100  is shown in accordance with a third example embodiment. Only the design of the piston and its associated aspiration chambers has been modified relative to the embodiment shown  FIGS. 3 and 4   a  to  4   d . Therefore, the control of solenoid valves  42  and  44  is the same as discussed above with reference to  FIGS. 4   a - 4   d.    
     As illustrated in  FIG. 6 , the lower pipette body  4  is still hollow so that it can house a double-section sliding piston  12 ′ in an appropriate cavity. The piston  12 ′ has an upper cylindrical portion  12   a  which is continued by a lower cylindrical portion  12   b  of smaller diameter. Portion  12   b  is guided by a section of the lower body  4   b  of complementary shape, while portion  12   a  is housed in concentric fashion and at a distance in a section of the upper body  4   a  of larger diameter. In addition, each of these two hollow sections  4   a ,  4   b  respectively has a fixed seal following the contour of the piston  12 ′ which slides relative thereto. The piston  12 ′ has a seal  17  which is fixed outwardly on its portion  12   a  and which follows the contour of the inner wall of the large section  4   a , while remaining housed under the upper seal  16  during the back-and-forth movement of the piston  12 ′. Thus, seal  17  moves with piston  12 ′. 
     With this configuration, the lower aspiration chamber  20  is delimited by the lower seal  14 , the lower end of piston  24 , the inner wall of section  4   b  and the wall  26  made in the pipette body  4 . In addition, the upper aspiration chamber  22  is delimited by the upper seal  16 , the inner wall of section  4   a , the piston portion  12   a , and the seal  17 . A variable volume space located between the seals  17  and  14  is not directly used for liquid sampling and dispensing, which means that it is not considered as an aspiration chamber unlike chambers  20  and  22 . 
     With this arrangement, chamber  20  has a constant cross section relative to axis  5 , in the shape of a disc of same axis and identical diameter as the inner wall of the small section  4   b . Also, chamber  22  is of constant cross section relative to axis  5 , in the shape of an annular ring of same axis having an outer diameter that is identical to that of the inner wall of the large section  4   a  and having an inner diameter identical to the outer diameter of section  12   a.    
     With this arrangement, by adequately determining the diameters of the two piston portions  12   a ,  12   b  and the inner diameter of section  4   a  of the lower pipette body, a cross section of the same value can be obtained for the two chambers  20  and  22 . Therefore, for a given displacement of the piston, an identical absolute value is obtained between the variation in volume in the lower chamber  20  and the variation in volume in the upper chamber  22 . 
     With reference to  FIG. 7 , a portion of sampling pipette  100  is shown in accordance with a fourth example embodiment. Only the design of the piston and its associated aspiration chambers has been modified with respect to the preceding embodiments shown in  FIGS. 3 ,  4   a  to  4   d , and  6 . Therefore, the control of the solenoid valves  42 ,  44  is identical or similar to one of those previously described. As can be seen in  FIG. 7 , the lower pipette body  4  is still hollow so that it can house the single section sliding piston  12 ″ in an appropriate cavity. Piston  12 ″, housed in said cavity, has an upper cylindrical portion guided by an upper body section  4   a  of complementary shape, the piston being continued by a lower cylindrical portion of same diameter housed concentrically and at a distance in a lower body section  4   b  of larger diameter. Also, the lower hollow section  4   b  fixedly houses the upper seal  16  and the lower seal  14 , which both follow the contour of the piston  12  which slides with respect thereto and is located at a distance radially inwardly with respect to the large section  4   b . Also, same piston  12 ″ has a seal  17  outwardly fixed to it which follows the contour of the inner wall of the large section  4   b , while remaining housed underneath the upper seal  16  during the back-and-forth movement of the piston. Similarly, it has a seal  19  fixed outwardly to it, which also follows the contour of the inner wall of the large section  4   b  while remaining housed underneath seal  17  and above the lower seal  14  during the back-and-forth movement of the piston. Thus, seals  17  and  19  move with piston  12 ″ while seals  14  and  16  are fixed to section  4   b.    
     With the configuration of  FIG. 7 , the lower aspiration chamber  20  is delimited by the seal  19 , the inner wall of section  4   b , the piston  12 ″, and the fixed seal  14 . Similarly the upper aspiration chamber  22  is delimited by the seal  17 , the inner wall of section  4   b , the piston  12 ″, and the fixed seal  16 . Chambers  20  and  22  have the same constant cross section relative to axis  5 , in the shape of an annular ring of same axis having an outer diameter identical to that of the inner wall of the large section  4   b , and an inner diameter identical to the diameter of the piston. Therefore, in this embodiment, for a given displacement of the piston  12 ″, an identical absolute value is also obtained between the variation in volume in the lower chamber  20  and the variation in volume in the upper chamber  22 . Additionally, the piston  12 ″ advantageously has a simple shape which facilitates its fabrication. 
     Ideally, the distance between seals  16  and  17  at the end of the upward stroke of the piston is equal to the distance between seals  14  and  19  at the end of the downward piston stroke, to obtain equal dead volumes in chambers  20  and  22 , and thereby, improve the symmetry of pipetting during movement of the piston in each of the two directions because the pipetted volume depends not only on the volume displaced by the piston but also on the dead volume. 
     With reference to  FIGS. 8   a - 9   b , a portion of sampling pipette  100  is shown in accordance with a fifth example embodiment. The design of the piston and its associated aspiration chambers is identical or similar to the embodiment shown in  FIG. 6  though it could be identical or similar to that of any of the other embodiments presented above without departing from the scope of the invention. 
       FIG. 8   a  shows the pipette  100  with its piston  12 ′ in a bottom position, whereas  FIG. 8   b  shows the pipette  100  with its piston  12 ′ in a top position. Two three-way solenoid valves  42 ,  44  are provided of the type incorporating a linear piston  52  and having three inlets  1 ,  2 ,  3 . By means of the movement of the linear piston  52  having a communicating groove, each solenoid valve is able alternately to set up fluid communication between inlets  1  and  2  and between inlets  2  and  3 , communication between inlets  1  and  3  being made impossible by construction. As mentioned above, these solenoid valves  42 ,  44  may be of the type marketed by LEE COMPANY under reference LHDA 053 1115H. 
     The first solenoid valve  42  is fixed to section  4   a  of the lower pipette body via a mounting plate  54  having three orifices  1 ′,  2 ′,  3 ′ respectively in permanent communication with the three inlets  1 ,  2 ,  3  of the solenoid valve secured to this mounting plate. Orifice  1 ′ communicates with the lower chamber  20  and with a connector  56  carrying a conduit  58 . Orifice  2 ′ communicates with the nozzle channel while orifice  3 ′ communicates only with a connector  60  carrying a conduit  62 . By way of indication, conduits  58 ,  62  may be replaced by channels made directly in the pipette body. 
     Similarly, second solenoid valve  44  is fixed to section  4   b  of the lower pipette body via a mounting plate  64  having three orifices  1 ′,  2 ′,  3 ′ respectively in permanent communication with the three inlets  1 ,  2 ,  3  of second solenoid valve  44  secured to this mounting plate. Orifice  1 ′ communicates with the upper chamber  22  and with a connector  66  connected to the other end of conduit  62 . Orifice  2 ′ communicates only with the exterior of the pipette, while orifice  3 ′ communicates solely with a connector  68  connected to the other end of conduit  58 . 
     As shown with reference to  FIG. 9   a , first solenoid valve  42 , when inlets  1  and  2  are in communication, ensures the first fluid communication A which provides free circulation of air between the lower chamber  20  and the nozzle channel  28  leading into the tip  30 . The air leaving chamber  20  circulates successively in orifice  1 ′, inlet  1  of first solenoid valve  42 , the piston groove, inlet  2  of first solenoid valve  42 , orifice  2 ′ of mounting plate  54 , and the nozzle channel  28 . When inlets  1  and  2  of the second solenoid valve  44  are in communication, the second solenoid valve  44  ensures the third fluid communication C allowing free circulation of air between the upper chamber  22  and the exterior of the pipette. The air leaving chamber  22  effectively circulates successively in orifice  1 ′ of the mounting plate  64 , inlet  1  of second solenoid valve  44 , the piston groove, inlet  2  of second solenoid valve  44 , orifice  2 ′ of the mounting plate  64 , and the exterior of the pipette. 
     As shown with reference to  FIG. 9   b , when inlets  2  and  3  of each of the solenoid valves  42 ,  44  are in communication, they jointly ensure both the second fluid communication B allowing free circulation of air between the upper chamber  22  and the nozzle channel  28  leading into the tip  30 , and the fourth fluid communication D allowing free circulation of air between the lower chamber  20  and the exterior of the pipette. 
     The air leaving chamber  22  circulates successively in orifice  1 ′ of mounting plate  64 , connector  66 , conduit  62 , connector  60 , orifice  3 ′ of mounting plate  54 , inlet  3  of first solenoid valve  42 , the piston groove, inlet  2  of first solenoid valve  42 , orifice  2 ′ of mounting plate  54 , and nozzle channel  28 . In addition, the air leaving chamber  20  successively circulates in orifice  1 ′ of mounting plate  54 , connector  56 , conduit  58 , connector  68 , orifice  3 ′ of mounting plate  64 , inlet  3  of second solenoid valve  44 , the piston groove, inlet  2  of second solenoid valve  44 , orifice  2 ′ of mounting plate  64 , and the exterior of the pipette. In fifth embodiment shown with reference to  FIGS. 8   a  to  9   b , control application  208  is programmed so that the functioning of the pipette is as described above, in particular regarding the automatic alternate establishing of fluid communications A and C and of fluid communications B and D. 
     As stated previously, the number of back-and-forth (up and down) movements of the piston depends on the quantity of liquid to be transferred. However, the pipette may be controlled conventionally for example using a single piston stroke to sample liquid and a single return piston stroke to dispense the liquid, even if this conventional operating mode is solely reserved for operations concerning small volumes of liquid. The described embodiments also support the sampling of greater volumes because the capacity of the pipette is no longer limited by the maximum stroke of the piston, nor by its diameter, nor by any other element of the pipette, since the number of back-and-forth operations of the piston dedicated to one same liquid sampling operation is in theory unlimited. Additionally, the large capacity associated with the pipette, which includes two chambers partly delimited by the piston, is in no way detrimental to the global ergonomics of the pipette, since the maximum stroke of the piston, irrespective of the maximum sampling capacity of the pipette, can be freely set at a reasonable value. 
     By way of example, if a maximum stroke in a given direction of the piston can sample 100 μl to an accuracy of 0.1 μl, the sampling of a liquid volume of 863.2 μl will be achieved with four back-and-forth movements of the piston, followed by a last partial stroke corresponding to 63.2 μl. One of the advantages, of course, lies in the fact that the sampling of 863.2 μl is obtained with an accuracy similar to the accuracy of a conventional pipette since it has a maximum piston stroke drawing a sample of 100 μl, which is greater than the accuracy of a conventional pipette for which the total volume of 863.2 μl has to be sampled during a single piston stroke. 
     Control application  208  determines the number of strokes and their length in relation to the volume to be sampled after entry by the user. The calculated data may optionally be displayed. Control application  208  may choose the maximum stroke offered by the pipette&#39;s design, with the exception of the last stroke which may correspond to only a fraction of the maximum possible stroke, so that the exact desired volume can be obtained. In an alternative embodiment, control application  208  may determine that a full stroke of the piston is made over a shorter length than the designed maximum length. In an example embodiment, the full stroke of the piston in each of the two sliding directions may result in the same quantity of liquid, though this is not necessary. 
     In alternative embodiments, instead of three-way solenoid valves other alternative solutions can be provided. For example, the opening/closing of each chamber with respect to the exterior may be provided by two “on/off” solenoid valves to ensure the alternate first and second fluid communications, while being synchronized with these latter means. More generally, each three-way solenoid valve may be replaced by two “on/off” solenoid valves also called two-way valves. 
     The word “example” is used herein to mean serving as an example, instance, or illustration. Any aspect or design described herein as “example” is not necessarily to be construed as preferred or advantageous over other aspects or designs. Further, for the purposes of this disclosure and unless otherwise specified, “a” or “an” means “one or more”. 
     The foregoing description of example embodiments of the invention have been presented for purposes of illustration and of description. It is not intended to be exhaustive or to limit the invention to the precise form disclosed, and modifications and variations are possible in light of the above teachings or may be acquired from practice of the invention. The embodiments were chosen and described in order to explain the principles of the invention and as practical applications of the invention to enable one skilled in the art to utilize the invention in various embodiments and with various modifications as suited to the particular use contemplated. It is intended that the scope of the invention be defined by the claims appended hereto and their equivalents.