Abstract:
Measurement device ( 10 ) for taking a liquid sample, comprising: a measurement portion ( 15 ) with a measurement surface ( 20 ), for being in use contacted with the liquid surface and a plug portion ( 40 ) having a plurality of electrical contacts ( 50 ), wherein the plug portion ( 40 ) is mountable to a socket ( 110 ) of a measurement evaluation apparatus ( 100 ).

Description:
FIELD OF THE INVENTION 
       [0001]    The invention relates to sensors for components in liquid samples. In particular, the invention relates to sensors for evaluating charged species concentrations, in particular ion concentrations, for example lithium ion concentrations, in samples, such as blood that can be easily handled by a user, i.e. a patient. 
       BACKGROUND AND RELATED ART 
       [0002]    Inorganic ions are an essential requirement for life and are found in large amounts in drinking water, blood and cells of an organism as well as in the environment. For example, the presence of many ions, e.g. sodium, potassium, magnesium, and calcium, inside and outside of the cells is essential for a living organism. Consequently, a measurement of the ion concentration in the blood and in blood cells of animals and human beings is of high importance for a large variety of body functions. 
         [0003]    Normally lithium is not at all or solely as a trace element present in the blood plasma, but it is also used as a drug to treat bipolar mood disorder. It is estimated that worldwide over one million people take lithium on a daily basis. A disadvantage in the use of lithium is the very low therapeutic index, i.e., the ratio between the toxic concentration and the therapeutic concentration. Most patients respond well to a blood plasma concentration of 0.4-1.2 mmol/L lithium while a lithium concentration of above 1.6 mmol/L is considered toxic. A prolonged high blood lithium level can result in permanent damage to the nervous system and even death. Monitoring of the lithium concentration during treatment is therefore essential, with regular checks every couple of months to keep the lithium level at desired level. 
         [0004]    The direct measurement of lithium in whole blood and the determination of inorganic cations in blood plasma have been described and demonstrated by E. Vrouwe et al. in  Electrophoresis  2004, 25, 1660-1667 and in  Electrophoresis  2005, 26, 3032-3042. Using microchip capillary electrophoresis (CE) with defined sample loading and applying the principles of column coupling, the concentration of alkali metals in the blood was determined in a drop of whole blood. Blood collected from a finger stick was transferred onto a chip without extraction or removal of components from the blood. The lithium concentration can be determined in the blood plasma from a patient on lithium therapy without sample pre-treatment. Using a chip with conductivity detection, a detection limit of 0.1 mmol/L has been obtained for lithium in a 140 mmol/L sodium matrix. 
         [0005]    In these disclosures, the components of the blood sample are separated electrophoretically inside a micro-channel. A double T injection geometry is used to select the ion components of interest and to guide them to detection electrodes. 
         [0006]    A method and an apparatus for measuring the ion concentration in liquid samples is disclosed in the co-pending PCT application PCT/EP2006/011148 the teachings of which are included by reference herewith. This PCT application describes an apparatus for the measurement of a concentration of a charged species in a sample, the sample comprising a plurality of types of charged species and at least one insoluble component, the apparatus comprising at least one channel with at least one opening with a filter function, at least two electrophoresis electrodes arranged along the at least one channel, and at least one sensor for measuring at least one type of charged species in the at least one channel. 
         [0007]    The dimensions of the opening and the channels used in such an apparatus are usually very small in order to reduce the amount of liquid necessary and the size of the apparatus. Typical channel dimension are in the order of less than 1 cm in width and less than 100 μm in depth. Consequently the apparatus can be quite small as well in order to minimize the amount of material used for the apparatus. The material is often expensive as for example glass. 
         [0008]    The apparatus should also be easily usable by a patient or other user. In particular, the patients suffering from bipolar mood disorder or similar illnesses, often suffer from quivering or shaking hands and encounter problems in handling small pieces. 
         [0009]    Furthermore blood sample and consequently the channels can be easily contaminated by blood or other liquids and can not be reused without intensive cleaning and sterilisation. 
         [0010]    In contrast, the known prior measurement devices are complex microfluidic and electronic components that are expensive and therefore not suited for one-time use only. 
         [0011]    It is an object of the present invention to provide a device and a method for easy handling of liquid sample measurement devices for measuring small samples. 
         [0012]    It is a further object of the invention to provide measurement devices that can be used as disposables while advanced measurement techniques can be employed. 
       SUMMARY OF THE INVENTION 
       [0013]    These and other objects of the invention are met by a measurement sample handling device and a method for taking a liquid sample according to the invention, wherein the measurement sample handing device comprises a measurement device and a handling unit. 
         [0014]    The measurement device for taking the liquid samples comprises: a measurement portion with a measurement surface for being in use contacted with the liquid sample and a plug portion having a plurality of electrical contacts, wherein the plug portion is mountable to a socket of a measurement evaluation apparatus. The measurement surface may be arranged at a different position of the measurement device than the plug portion in order to avoid liquid of the liquid sample to come into contact with the electrical contacts. In particular, the plug portion may be arranged at a different side of the measurement device, than the measurement surface. 
         [0015]    The measurement surface and the measurement portion may be made form the same material, for example from glass and may be realized in one piece. The measurement device may further comprise a plurality of electrodes coupled to the electrical contacts. The measurement device may neither have any active electrical components, such as switches, transistors nor an electrical power supply. In some cases the measurement device may comprise some passive electrical components such as temperature sensors or the like. 
         [0016]    During assembly, the measurement device might be inserted into a handling unit the handling unit having a first opening for the measurement surface and at least a second opening for the plurality of electrical contacts. Thus when inserted into the handling unit, the measurement surface is accessible by a user or patient for placing a liquid sample. On the other side the plug portion is accessible through the second opening of the handling unit for allowing access to the electrical contact, for example by a socket. Thus, the handling unit may form an electrical contact seal for preventing liquid to come into contact with the electrical contacts at the plug portion of the measurement device. 
         [0017]    The handling unit may not comprise any electrical components as all electrical contacts are provided by the measurement device. In some cases, however, the handling unit may comprise electrical contacts and electrical components. 
         [0018]    The handling unit may be substantially large in size than the measurement device. Thus the handling unit can be of handy size for easy and safe handling of the measurement sample handling device even by patients suffering from shaking hands or similar. In the same time the measurement device can be kept small in order to minimize the amount of liquid sample necessary for reliable measurements. In addition the smaller measurement devices may be cheaper to produce. The measurement sample handling device can thus be a disposable device that is for few time or one-time use. This is in particular useful if the liquid sample is a body fluid such as blood or another sample that requires sterile and/or clean environment. 
         [0019]    The handling unit may also be adapted to accommodate a plurality of measurement devices, for carrying out a plurality of sample measurements in a row or in parallel. The measurement device may also be positioned at a particular side of the handling unit, for example such that the second opening provides in use easy access to the plug portion from the outside, for example by a plurality of electrical pins, when the measurement sample handling device is inserted into a socket of a measurement evaluation device. The plurality of electrical pins may be arranged to come into electrical contact with the plurality of electrical contacts of the measurement device, when the measurement device or the measurement sample handling device is mounted to the socket. 
         [0020]    The measurement evaluation device for evaluating at least one parameter of the liquid sample may comprise a power supply for the measurement device and all further electric and electronic means to carry out a measurement for evaluating the at least parameter. In particular, the measurement evaluation device may comprise control means for controlling and monitoring the electrodes in the measurement device, when the measurement device is inserted into the socket. 
         [0021]    The invention also comprises a method for evaluating at least one parameter of a liquid sample comprising: placing the liquid sample on a measurement surface of a measuring device, wherein the measuring device has a plurality of electrical contacts, inserting the measuring device into a socket having a plurality of electrical pins such that at least some of the plurality of electrical pins come into contact with at least some of the plurality of electrical contacts, and determining the at least one parameter by electrical measurements. 
         [0022]    The measurement device may also be part of a measurement sample handling device and comprise a handling unit. 
         [0023]    The method can be advantageously applied by patient or elderly users, even with shaking hands. A liquid sample, such a blood sample or another body fluid is placed on the measurement surface prior to insertion of the measurement device into the socket. Thus, no electrical power is present in the measurement device when handling the liquid sample. Furthermore, a measurement of the liquid sample can only be started once placing of the sample on the measurement surface has been finished. In some cases, the measurement surface may be concealed by a closure device to protect the liquid sample and/or to prevent evaporation. 
         [0024]    The invention also comprises a method for the assembly of the measurement sample handling device, the method comprising: filling at least one channel in a measurement device having a measurement surface and a plug portion, with a solution, the at least one channel having at least one channel opening in the measurement surface, inserting the measurement device into an opening of a handling unit, such that the measurement surface of the measurement device is accessible, and closing the channel opening with a protective layer to be removed prior to use of the measurement device. 
         [0025]    This allows for easy fast and cheap production of the measurement sample handling device. 
         [0026]    The insertion of the measurement device into the handling unit may be performed through the first opening. The measurement device may also be inserted through a third opening, for example on the opposite side of the handling unit. The second opening may also be enlarged or combined with the third opening to enable insertion of the measurement device into the handling unit. 
         [0027]    Inserting the measurement device into the opening of the handling unit and closing or sealing the channel opening which may be performed directly after filling the at least one channel in order to prevent evaporation of the liquid. 
         [0028]    The measurement environment may also be kept in a wet or humid environment prior to closing or sealing the channel opening may be performed directly after removing the measurement device from the wet or humid environment. 
         [0029]    The at least one channel in the measurement device may be filled with a solution prior to use. The solution may be an electrolyte solution (BGE). The solution may also comprise an electroosmotic flow suppressing substance or a dynamic coating such as poly vinyl alcohol (PVA). 
         [0030]    The term prior to use is in this respect understood as being prior to use of the measurement sample handling device by a patient or a user. Prior to use may also include prior to shipment to the user or the patient. 
     
    
     
       DESCRIPTION OF THE DRAWINGS 
         [0031]    The invention may be better understood with respect to the figures and the detailed description of preferred embodiments, which is illustrative only and not limiting to the invention and wherein: 
           [0032]      FIG. 1  shows a measurement system according to the invention comprising a measurement evaluation device with a socket for a measurement sample handling device comprising a handling unit and a measurement device. 
           [0033]      FIGS. 2   a  to  2   c  show the disposable device according to the invention in an exploded view, assembled and a portion of the disposable device in greater detail. 
           [0034]      FIGS. 3   a ,  3   b , and  3   c  show the measurement device in a perspective view, side view and top view, respectively. 
           [0035]      FIG. 4  shows a schematic view of the measurement device in greater detail. 
           [0036]      FIG. 5  shows a detailed view of a specific embodiment of two openings of the measurement device. 
           [0037]      FIG. 6  shows the plurality of electrical contacts of the measurement device according to the invention in more detail 
           [0038]      FIG. 7  shows the socket of measurement evaluation device in greater detail. 
           [0039]      FIGS. 8   a  and  8   b  shows a finger tip positioning tool on the handling unit and a plurality of opening and control electrodes at the opening. 
           [0040]      FIG. 9  shows a cross sectional view of the handling unit with the measurement device inserted and a sealing droplet. 
           [0041]      FIGS. 10   a  to  10   c  show variants of the sealing and a sealing droplet attached to the measurement device. 
           [0042]      FIG. 11  shows the handling unit with a locking device for fixing the measurement device in the handling unit. 
           [0043]      FIGS. 12   a  and  12   b  show the insertion of measurement device into the handling unit through a third opening in the handling unit. 
           [0044]      FIG. 13  shows a locking mechanism for closing the handling unit with the closure device. 
       
    
    
       [0045]    In the figures same reference numerals describe the same or similar objects. 
       DETAILED DESCRIPTION OF THE INVENTION 
       [0046]      FIG. 1  shows a measurement system comprising a combination of a measurement evaluation apparatus  100  having a socket  110  and a measurement sample handling device or disposable device  1  comprising a measurement device  10  (shown in  FIG. 2   a ) attachable to the socket  110 . The measurement evaluation apparatus  100  comprises electronics for computing and evaluating a species ion concentration taken from a sample in the measurement sample handling device  1 . The measurement evaluation apparatus  100  may comprise controls for controlling and checking the measurement and evaluation process. The measurement evaluation apparatus  100  may also comprise indication means, such as a display or similar, to indicate results and setting of the measurement system to a user. The indication means is not shown in the figure. The measurement evaluation apparatus  100  may also comprise interfaces for connecting the measurement system to a computer or a clinical data system (not shown) for data transfer and measurement system control. The measurement evaluation device  110  may also be a personal computer equipped with a socket  110  for receiving the measurement sample handling device  1 . 
         [0047]    The measurement sample handling device may be a one-time use disposable that is only used for one measurement. The disposable device may, however, also be used for several times, for example for repetitive or parallel measurements. The terms disposable device and measurement sample handling device are used as synonyms within this disclosure. 
         [0048]      FIGS. 2   a  to  2   c  show the measurement sample handling device  1  in more detail. In  FIG. 2   a  an exploded view is illustrated, an assembled view is illustrated in  FIG. 2   b  and in  FIG. 2   c  the portion of the measurement sample handling device  1  that can be attached to the socket  110  is illustrated in greater detail. The measurement sample handling device  1  also comprises a handling unit  200 . The handling unit  200  has a first opening  210  on a first side  202 , defined to be the measurement side, and a second opening  220  at a second side  204  of the handling unit  200  as illustrated in  FIGS. 2   a  and  2   c . The second surface  204  faces towards the socket  110  of the measurement evaluation device  100  when the measurement sample handling device  1  is mounted in the measurement evaluation apparatus  100 . The first opening  210  and the second opening  220  may also be arranged at the bottom face, at the edge of the bottom face and the second face  204  of the handling unit  200  or at any other side of the handling unit  200 . The openings may also be enlarged in size to enable the insertion of the measurement device  20  into the handling unit  200 . 
         [0049]    The first opening  210  and the second opening  220  are interconnected inside the handling unit  200  as illustrated by the dotted lines in  FIGS. 2   a  and  2   c.    
         [0050]    The measurement device  10  is inserted into the first opening  210  of the handling unit  200 . The measurement device  10  has a measurement surface  20  and a plug portion  40 . The measurement device  10  may also be inserted through second opening  220  or a third opening  230  as will be explained with respect to  FIGS. 9 and 12   a,b.  The measurement surface  20  is substantially in the same plane as the first side  202  of the handling unit  200  when the measurement device  10  is inserted in the handling unit  200 . Thereby, the plug potion  40  is accessible from the outside of the measurement sample handling device  1  through the second opening  220  of the handling unit  200 . The measurement device  10  is described in further detail below with respect to  FIG. 3 . 
         [0051]    The measurement device  10  may be made from a different material that the handling unit  200 . In particular, the measurement device  10  may be made partially or completely from glass material, whilst the handling unit  200  is made from plastics material. 
         [0052]    The measurement device  10  may also be formed from polymer material. 
         [0053]    The measurement device  10  is much smaller in size than the handling unit  20 . Thus millimetre dimensions of the measurement device  10  may be implemented, while the measurement device  10  can be easily handled with the handling unit  200 . The size of the handling unit  200  can be adapted to the needs of the user (patient). For example, the handling unit  200  may have dimensions that provide an easy handling even with shaking hands. For example, the size of the handling unit  200  may be larger than 1 cm, in particular about 4 cm or more in at least one dimension. In addition, at least the second side  204  of the handling unit  200  is adapted to fit into the socket  110 . The side faces or other geometrical parameters of the handling unit  200  may also be adapted to fit into the socket  110 . 
         [0054]    The socket  110  and the handling unit  200  may be formed in a way that there is only one possibility of inserting the disposable or measurement sample handling device  1  comprising the handling unit into the socket  110 . Thereby faulty operation by unexperienced or elderly users or patients can be excluded and measurement errors can be avoided. 
         [0055]    The measurement device  10  may be arranged close to the second side  204  when inserted inside the handling unit  200 . Thus, the measurement device is close to the socket  110  when the measurement sample handling device  1  is inserted into the socket  110 . The measurement device  10  may be arranged inside the handling unit  200  such that side of the measurement device  10  comprising the plug portion  40  is parallel to the second side  204  when inserted into handling unit  200 . 
         [0056]    The handling unit  200  and the measurement surface  20  might be covered by a permeable layer  32  (as seen clearly in  FIG. 2   a ) for providing access to the measurement surface  20  of the measurement device  10 . The permeable layer  32  may completely or partially cover the measurement side  202  and the measurement surface  20 . 
         [0057]    A sealing  34  is provided on top of the measurement side  202  for sealing the permeable layer  32  or the measurement surface  20  for preventing leakage or evaporation of fluids. The sealing layer  34  may be removed by the patient or user prior to use of the measurement device. The permeable layer  32  and the sealing  34  may be of different size. A person skilled in the art will understand that more or fewer layers may be arranged on top of the measurement surface  20  or the first surface  202 . 
         [0058]    A closure device  30  may be used for closing the measurement surface  20  prior to and/or after use. The sealing  34  and permeable layer  32  may be attached to the measurement device  10 , the closure device  30  or to the handling unit  200 . 
         [0059]    The handling device  200  and the closure device  30  may be made from the same material, for example plastics material. The handling device  200  and the closure device  30  may also be made in one piece. An integral hinge may be provided for separating the closure device portion form the handling device portion and for enabling folding of the closure device on top of the handling device in order to conceal or close the measurement surface  20 . 
         [0060]      FIGS. 3   a ,  3   b , and  3   c  show the measurement device  10  in a perspective view, a side view and a top view, respectively. 
         [0061]    The measurement device  10  has a first opening  25  in the measurement portion  15 . A microfluidic channel  60  (shown in  FIG. 4 ) is implemented in the measurement portion  15  inside the measurement device  10 . The first opening  25  provides an access from the surroundings of the measurement surface  20  to the microfluidic channel  60 . A person skilled in the art will understand that a plurality of openings  25  can be provided and that the microfluidic channel  60  can comprise a network of different ones of the channels  60  which are realized in the measurement device  10 . An example for a channel  60  with a first opening  25 , that is particularly useful with the present invention can be found in the patent application PCT/EP2006/011148. The measurement device  10  may be at least partially formed in glass material or another material that can be microstructured. 
         [0062]    The first opening  25  may be in the measurement surface  20 . The first opening  25  may also be in another side of the measurement portion  15  of measurement device  10  in close proximity to the measurement surface  20  to which the liquid sample is applied. In this case the liquid sample will go from the measurement surface  20  to the first opening  25   
         [0063]    The plug portion  40  is arranged at a different side of the measurement device  10  than the measurement surface  20  comprising the first opening  25 . Thus, when inserted into the handling unit  200 , the plug portion  40  is only accessible through the second opening  220  of the handling unit  200  while the measurement surface  20  is solely accessible through first opening  210  of the handling unit  200 . The handling unit  200  may thus provide a seal that ensures that the liquid sample that is in use added to the measurement surface  20  can not come into contact with any of the plurality of electrical contacts  50 . Thus, electrical short-circuits between two or more of the plurality of contacts  50  that would impair a measurement or control of functions of the measurement device  10  can be advantageously excluded. 
         [0064]    The plug portion  40  and the measurement surface  20  may also be arranged on the same side of the measurement device  10 . However, the plug portion  40  and the measurement surface  20  are separated form each other by a sealing portion of the handling unit  200  when the measurement device  10  is inserted into the handling unit  200 . Thus, liquids on the measurement surface  20  are prevented from coming into contact with electrical contacts of the plug portion  40 . 
         [0065]      FIG. 4  shows a schematic view of the measurement device  10  in the view of  FIG. 3   b  in greater detail. The microfluidic channel  60  is arranged between two microfluidic reservoirs  61  and  62 . The microfluidic channel  60  further has the first opening  25  in the measurement surface  20 . The first opening  25  may be connected via a sample channel  26  with the microfluidic channel  60 . 
         [0066]    In addition, electrodes  65  may be integrated in the measurement device  10 . The electrodes  65  may be constructed as electrophoresis electrodes  65   b  and  65   c  for separating charged species in the sample inside the microfluidic channel  60 . An electrophoresis electrode  65   b  may be integrated in each ones of the reservoirs  61 ,  62 ,  64 . The reservoirs  61 ,  62 ,  64  may be closed, such that the microfluidic channel  60  provides the only access to the reservoir  61 ,  62   64  In this way the liquid inside the reservoir is prevented from evaporation and gas formation. The reservoirs  61 ,  62 ,  64  may be substantially larger in size that the width, height or depth of the microfluidic channel  60 . 
         [0067]    Each ones of the electrodes  65   b  are in electrical contact via electrical path with electrical contact  50   b,    50   h  and  50   g,  respectively. Thus electrophoresis inside the microfluidic channels  60  can be controlled by applying voltages independently to each ones of the electrophoresis electrodes  65   b  by the measurement evaluation device  100  when the measurement device  10  is attached to the socket  110 . The opening electrode  65   c  may be integrated at the first opening  25  and connected with electrical contact  50   i.  The opening electrode  65   c  may also serve as an electrophoresis electrode or as a control electrode as will be explained later. 
         [0068]    The electrodes  65  may also be provided as conductivity electrodes  65   a  for measuring the conductivity in a section of the microfluidic channel  60  for determining a charge concentration in this section of the microfluidic channel  60 . The conductivity electrodes  65   a  are connected to and addressed by electrical contacts  50   a  and  50   d  (as illustrated in  FIG. 4 ) and thus controlled by measurement evaluation device  100  when the measurement device  10  is attached to the socket  110 . 
         [0069]    The electrophoresis electrodes  65   b  in capillary electrophoresis system may be based on material that can adsorb hydrogen atoms due to its intrinsic characteristics, for instance palladium or platinum. The adsorption makes it possible to prevent gas formation for example of hydrogen near the electrophoresis electrode  65   b  used as a cathode. 
         [0070]    The use of palladium or platinum as material is in particular useful for the electrophoresis electrode  65   b  used as a cathode but the other ones of the electrodes  65  may also be made from the same material. 
         [0071]    The electrophoresis electrode  65   b  and/or the opening electrode  65   c  used as anode may also be made from a different material in order to prevent oxygen gas formation. For instance, the electrophoresis electrode  65   b  used as anode may be a silver/silver chloride electrode or may be made from copper. In this case, chloride and solid silver or copper ions will be formed instead of oxygen. 
         [0072]    Palladium, platinum, nickel, silver/silver chloride and/or copper as well as further materials may also be mixed in one or more of electrodes  65  to combine the advantages of each material. 
         [0073]    One or more of the electrodes  65 ,  65   a,    65   b,    65   c  may also be provided with an adhesive layer made from en inert metal such as tantalum or chrome. 
         [0074]    The measurement device  10  may further comprise electric components, such as temperature sensors, pH sensors and others that may be electrically contacted and controlled with the remaining electrical contacts  50   c,    50   c  and  50   f.  It is obvious to a person skilled in the art that the number of the plurality of electrical contacts  50 ,  50   a  to  50   i  is purely exemplary and that more or less electrical contacts can be provided within the scope of the invention. 
         [0075]    It is an advantage of the present invention that the measurement device  10  can comprise solely passive electrical components such as wires, conductors and electrodes. No active component, such as transistors, diodes, flip-flops or similar other active electronic components are necessary. The measurement device  10  may be electronically controlled by the measurement evaluation device  100 . However, sensors may be integrated into measurement device  10  that can comprise semiconductor elements that may also be active semiconductor elements in some cases. 
         [0076]      FIG. 5  shows a detailed view of a specific embodiment of the first opening  25  of the measurement device  20  that is connected to the microfluidic channel  60  by the sample channel  26 . In addition, a second opening  27  may be provided, for example to prevent evaporation of fluids. The second opening  27  is fluidly connected to the sample channel  26  and the first opening  25 . The second opening  27  may be substantially larger in size than the first opening  25 . The difference in size results in different contact angles □ 1  and □ □  at first opening  25  and second opening  27 , respectively, when a liquid is filled into the microfluidic system and sample channel  26 . The difference in the contact angle □ 1  and □ □  will result in a pressure difference in the first opening  25  and the second opening  27  that will, when the liquid is allowed to evaporate from the first opening  25  and the second opening  27 , result in the level of the liquid remaining at essentially the same level in first opening  25  while the liquid level goes down in second opening  27  due to evaporation. 
         [0077]    A person skilled in the art will understand that further openings with different of identical sizes can be added on order to modify the evaporation behaviour at the first opening  25 . 
         [0078]      FIG. 6  shows the plurality of electrical contacts  50  in more detail. Each of the plurality of electrical contacts  50  may be arranged inside a hole  42  formed in the plug portion  40  of the measurement device  10 . For example an electrical contact may be provided at the bottom of the hole  42 . As illustrated each one of the plurality of electrical contacts  50  will be positioned in a separate hole  42 . In some cases, two or more of the plurality of electrical contacts  50  may also be arranged together in a single one of the holes  42 . In some cases, holes  42  may be provided without any contacts in case the measurement device  10  provides only some functionality. For example, the electrical contacts  50   d,    50   e  and  50   f  shown in  FIG. 4  may be left out if no further electrical component are used. However, the plug portion provides corresponding holes  42  providing space for the corresponding pins of the socket  110 . 
         [0079]    The hole  42  may be round and of cylindrical shape or conical shape or have any other shape known to a person skilled in the art. The conical shape may be used to align or guide pins of the socket  110  towards each of the plurality of contacts  50 . Other shapes of the holes  42  may also be implemented within the scope of the invention. 
         [0080]    Furthermore, the layout or arrangement of the electrical contacts may be varied and is by no means limited to the line-arrangement illustrated in the Figures. 
         [0081]    It is a feature of the present invention that all electrical contacts of the measurement sample handling device  1  are arranged in the measurement device  10  and that the handling unit  200  does not comprise any electrical components, such as contacts, wiring etc. 
         [0082]      FIG. 7  shows the socket  110  of measurement evaluation device  100  in greater detail. The socket  110  may be provided in a side wall of the measurement evaluation device  100  as illustrated in  FIG. 1  or may be provide in a separate socket container that is electrically connectable to the measurement evaluation device  100 . 
         [0083]    The socket  110  comprises a plurality of pins  120  that is arranged in a pattern corresponding to the plurality of contacts  50  of the measurement device  10  such that when the measurement sample handling device  1  is inserted into the socket  110 , at least a portion of the plurality of pins  120  comes into electrical contact with at least one of the plurality of contacts  50 . The number of the plurality of pins  120  may be inferior, equal or superior to the number of contacts  50  of the measurement device  10 . Thus, the same socket  110  and consequently the same measurement evaluation device  100  may be used with a plurality of different measurement devices  10 . The measurement devices  10  may differ in the number of electrical contacts  50 , for example due to additional sensors, like temperature, pH sensors or similar, that are integrated in the measurement device  10 , or due to a different number of electrodes  65  for different applications of the measurement device  10 . Although the number of electrical contacts  50  may vary, the number and shape of the holes  42  in the plug portion  40  might be adapted to the number and shape of pins  120  in the socket  110  in order to provide correct contact and positioning for each of the pins  120  when the measurement sample handling or measurement sample handling device  1  with the measurement device  10  is inserted into the socket  110 . 
         [0084]    The plurality of pins  120  may be made of electrical spring contacts in order to ensure the contact of the plurality of pins  120  with the corresponding ones of the plurality of electrical contacts  50  when the measurement device  100  is inserted into the socket  110 . The spring contacts may recede and thus prevent damage on the measurement device  10 , when the measurement device  10  is inserted into the socket  110  and the electrical contacts  50  are forced against the pins  120 . 
         [0085]    The plurality of pins  120  may be arranged inside the socket  110  as illustrated in  FIG. 6 . Thus, when the measurement sample handling device  1  or solely measurement device  10  is introduced into the socket  110 , the measurement device  10  is completely or partially positioned inside the socket  110 . In this case no modification to the sample on the measurement surface is possible after the measurement is started and no electric contacts are necessary in the handling unit  200  while keeping the measurement device  10  small and therefore cheap 
         [0086]    In addition, a direct electrical connection with a patient or other user is impossible. Therefore the measurement device can be safely used by a patient or other user without specific training or care. This is important because high voltages, e.g. in the range or 1000 Volts may be used during measurement of the sample. 
         [0087]    The measurement evaluation device  100  may only start a measurement when the measurement sample handling device  1  with the measurement device  10  is inserted correctly into socket  110 . For example, a measurement may only be started if the required ones of the contacts  50   a  to  50   i  are actually in contact with the corresponding pins. 
         [0088]    The actual measurement may only be started after successful control measurements are carried out in order to ensure correct operation of the measurement device  10 . A control measurement may be for example measuring the sodium concentration in the liquid sample  5 . The sodium concentration may be measured and evaluated substantially in parallel to the actual measurement of the lithium concentration. For a successful control measurement, the sodium concentration has to be in a range corresponding to that which is usually found in blood. In case a different sodium concentration is evaluated, something went wrong in the measurement and it can not be ensured that the evaluated lithium concentration is correct. The measurement would therefore be ignored. 
         [0089]    Additional and initial controls can be performed, for instance measuring the conductivity or the temperature of the background electrolyte solution (BGE), in order to check the correctness of for example sodium concentrations. 
         [0090]      FIG. 8   a  shows a specific embodiment of the invention with a finger tip positioning tool integrated in the handling unit  200  described in detail above with respect to  FIGS. 2   a  to  2   c . A rim  212  is provided on one or more sides of the first opening  210  in the measurement side  202  of the handling unit  200 . The rim  212  has the shape and height that it can easily be felt and or seen by a user (patient) using the measurement sample handling device  1  when putting a finger on top of the measurement side  202 . The rim  212  may be arranged along the first opening  210  around the position, at which the opening  25  is located when the measurement device  10  is inserted into the handling unit  200 . The rim  212  may thus serve as a positioning tool for depositing a liquid or blood sample onto the opening  25  at the measurement surface  20 , as it may be felt by the finger tip of a user or because the rim may be simply seen by eye. This is in particular useful because the opening  25  itself may be too small to be seen by the user (patient) by eye. 
         [0091]    A cavity or groove in the measurement surface  20  may also be used as positioning tool. The cavity or groove has the further advantage that the cavity or groove serves as collector for sample liquid and that can prevent sample liquid from leaking or spreading onto the measurement device. 
         [0092]    The opening electrode  56   c,  present at the first opening  25  as illustrated in  FIG. 4  or  FIG. 8   b , may be used to detect the presence of sample liquid on or around the first opening  25 . For example, the opening electrode  65   c  can be present at a certain position or height within the positioning cavity or groove. Thus the presence of a sample liquid  5 , and moreover, the presence of a certain amount of sample liquid can be checked in order to ensure that the required amount of sample liquid has been added, that is necessary for reliable measurements. 
         [0093]      FIG. 8   b  shows an example how additional electrodes can be arranged at the first opening  25 . In addition to the opening electrode  65   c,  at least one control electrode  65   d,    65   e,  and  65   f  can be used. The at least one control electrode  65   d,    65   e,    65   f  can be arranged close to the first opening  25 , for measuring additional parameters such as conductivity of the liquid sample. For example, the conductivity of a liquid sample can be measured between the control electrode  65   d  and the control electrode  65   e.  The electrode  65   f  can be from a different material or can have a coating for measuring a different parameter of the liquid sample. 
         [0094]    A channel electrode  65   g  may be provided in proximity to the first opening  25 . The channel electrode  65   g  is in contact with the solution inside the sample channel  26 , when the sample channel is filled with an electrolyte solution. In case evaporation of the electrolyte solution should occur, the level of the electrolyte solution would sink below the channel electrode  65   g,  which can be easily detected by conductivity measurements. 
         [0095]    The channel electrode  65   g  as well as the opening electrode  65   c  and the control electrodes  65   d,    65   e,  and  65   f  can thus be used for initial control measurements as for instance as indication for initial conductivity or evaporation and or gas bubble detection. 
         [0096]    The opening electrode  65   c  or the control electrode  65   d,    65   e  or  65   f  or the channel electrode  65   g  may also be used as electrophoresis electrode, for example for capillary electrophoresis inside the sample channel  26 . 
         [0097]      FIG. 9  shows a cross sectional view of the handling unit  200  with the measurement device  10  inserted. Prior to use, a sealing droplet  29  may be placed at least on top of the opening  25 . The sealing droplet  29  may be from silicone, PDMS or other material and covers the opening  25  and thus the microfluidic channel  60  in order to prevent evaporation and contamination. The sealing  34 , described above with respect to  FIG. 2   a , may be a sticky foil for covering the measurement surface prior to use. The sealing droplet  29  may stick to the sticking foil. The user (patient) may remove the sticky foil and in the same time the sealing droplet  29  sticking to it, thereby providing access to the opening  25 . 
         [0098]      FIGS. 10   a  to  10   c  show different arrangements of the sealing  34  and the sealing droplet  29  on the first opening  25  of measurement device  10 . As illustrated in  FIG. 10   a , a sealing droplet  29 , that may be from silicon material or the like, may be placed on the first opening  25  after the microfluidic network comprising the microfluidic channel  60  and the sample channel  26  has been filled with a liquid prior to use of the measurement device  10 . The sealing droplet  29  thus prevents any evaporation of liquid from the microfluidic network through the first opening  25 . A further sealing  34 , for example in form of a tape or foil may be applied on top of sealing droplet  29 . When a patient or user wants to use the measurement device  10 , he removes the sealing  34  and the sealing droplet  29  away, before applying the liquid sample  5  to the first opening  25 . The sealing droplet  29  may be attached to the sealing  34  in order to facilitate its removal. 
         [0099]    The sealing  34  may also comprise a hole  35  aligned substantially on top of the first opening  25  when the sealing  34  is placed on the measurement surface  20  of measurement device  10  as illustrated in  FIG. 10   b . In this case, the sealing droplet  29  may extend through the hole  35  in the sealing  34  for secure attachment. Thus the sealing droplet  29  is removed form the first opening  25  when a user or patient removes the sealing  34  prior to use of the measurement device  10 . 
         [0100]    The sealing  34  may also be directly attached to the measurement surface  20  of measurement device  10 . The sealing  34  may thus directly seal the first opening  25 . The sealing may be a tape or a foil, made from or covered by silicone or other suitable material. 
         [0101]    The sealing  34  and eventually the sealing droplet  29  may also be attached to the closure device  30 . In this case, the sealing is removed when the closure device  30  is opened prior to use of the measurement device  10 . The sealing may also be applied when closing the closure device  30  after placing the liquid sample  5  on the measurement surface  20  in order to prevent contamination and evaporation of the liquid sample  5 . 
         [0102]    A person skilled in the art will understand that the sealing  34  described above with respect to the first opening  25  can also be applied to further openings in the measurement device  10 , for example to the second opening  27  illustrated describe with respect to in  FIG. 5 . 
         [0103]      FIG. 11  shows the handling unit  200  of the present invention with a locking device  214  for fixing the measurement device  10  in the handling unit  200 . The measurement device  10  may be inserted through first opening  210  into handling unit  200 , as illustrated in  FIG. 2   a . A locking device  214  in form of a rim may be provided at the opening  210 . Thus, the width of the opening  210  in at least one direction may be somewhat smaller or equal to the corresponding size of the measurement device  10 . The locking device  214  may serve as a fixation or snap-in mechanism for the measurement device  10  in the handling unit  200 . 
         [0104]      FIGS. 12   a  and  12   b  shows the insertion of measurement device  10  into the handling unit  200  through a third opening  230  provided in the handling unit  200 . The third opening may be provided on an opposite side to first side  202  of handling unit  200 . Thus, the first opening  210  in handling unit  200  can be smaller in size and provide essentially only access to the first opening  25  on the measurement surface  20 . In this way, the contact seal for preventing sample liquid form coming into contact with the plug portion  40  can be substantially large in size. Furthermore, positioning of the measurement surface  20  and the first opening  25  can be carried out more precisely. 
         [0105]    The third opening  230  may also be combined with the second opening  220  to form one enlarged opening for the plug portion  40  and the insertion of the measurement device  10 . 
         [0106]    A locking device  234  that may be snap-in mechanism is provided at handling unit  200  and/or measurement device  10  in order to ensure fixation and correct positioning of the measurement device  10  inside the handling unit  200 , as illustrated in  FIG. 12   b . The seal  34 , the permeable layer  32  or other means provided in the handling unit  200  may provide a counterforce for when the measurement device  10  is inserted to ensure the closure of the first opening  25  in order to prevent contamination and evaporation 
         [0107]      FIG. 13  shows a locking mechanism for closing the handling unit  200  with the closure device  30 . The closure device  30  may be provided with a hook  38 , that may engage with a corresponding notch  238  at the handling unit  200 , when the closure device  30  is positioned on the first surface  202  of handling unit  200  in order to cover and protect the measurement surface  20  and opening  25 , in particular after a liquid sample has been placed on the opening  25  of the measurement device  10 . The hook  38  and the notch  238  may engage with each other in non-removable manner forming a snap-in locking device. In this case, after closing the closure device  30 , the handling unit  200  can not be reopened and thus not be reused. This prevents contamination of the sample as well as falsification of the measurement results. 
         [0108]    It is obvious that other snap-in or locking mechanisms can be used with the invention. For example, the locking mechanism may be provided as a mechanism that can be opened and closed several times for allowing multiple access to the measurement surface. Such mechanisms are commonly known and widely used. 
         [0109]    The invention has been described with respect to several embodiments. It will, however, be clear to those skilled in the art that the invention is not limited thereto. Rather the scope of the invention is to be interpreted in conjunction with the following claims.