SENSOR UNIT AND CELL CULTURE ANALYZING DEVICE PROVIDED WITH SAME

A sensor unit includes a sensor, a probe, and a probe holder. The probe makes contact with electrodes of a connection terminal part of the sensor and applies a specific voltage. The probe holder holds the probe so that the probe protrudes toward the connection terminal part of the sensor, has an opposing surface that is disposed opposite the connection terminal part of the sensor, and forms a non-capillary space between the opposing surface and the connection terminal part of the sensor to allow communication with the space facing the adjacent electrodes of the connection terminal part of the sensor.

TECHNICAL FIELD

The present invention relates to a sensor unit for analyzing cultured cells, and to a cell culture analyzing device provided with the same.

BACKGROUND ART

A conventional cell culture analyzing device is configured such that a measurement device is disposed inside an incubator, a culture module equipped with a sensor and in which cells are cultured is placed in the measurement device, and in this state the progress of the cell culture is measured (the culture status is analyzed) using a glucose sensor while the cells are being cultured.

For instance, Patent Literature 1 discloses a cell culture device including a plurality of culture units, each including a canister that is disposed in a thermostatic bath, and a culture cassette that is housed in the canister.

With the cell culture device disclosed in Patent Literature 1, the culture cassette has a culture bag containing cells to be cultured, and is inserted into the canister. The cells in the culture bag are cultured in an independent culture environment for each canister.

CITATION LIST

Patent Literature

Patent Literature 1: International Patent Application No. WO 2007-052716

SUMMARY

Technical Problem

However, the following problem is encountered with the above-mentioned conventional cell culture device.

With the cell culture device disclosed in the above publication, no consideration whatsoever is given to the occurrence of leakage current attributable to condensation between the measurement electrodes that occurs on the surface of the sensor used in an environment of high temperature and high humidity.

For example, when a sensor that has been placed under a room temperature (25° C.) environment has been immersed in a culture medium in a culture container and is then placed in an environment of high heat and humidity in an incubator (37° C., humidity of at least 90%), the temperature of the sensor surface will remain close to room temperature for a time, and is therefore lower than the temperature inside the incubator. Consequently, condensed moisture on the sensor surface may electrically connect the measurement electrodes, resulting in current leakage.

If such a current leak should occur between the measurement electrodes in a cell culture analyzing device that measures minute currents to perform cell culture analysis, etc., there is the risk that various kinds of measurement cannot be performed with high accuracy.

It is an object of the present invention to provide a sensor unit and a cell culture analyzing device provided with the same, with which the occurrence of leakage current attributable to condensation can be effectively suppressed even when the device is used in an environment of high temperature and high humidity.

Solution to Problem

The sensor unit according to the first invention is a sensor unit for measuring components of a liquid sample placed in a culture container, including a sensor, a connection part, and a connection part holder. The sensor has a main body, a sensing part that is disposed on the main body and is immersed in the liquid sample, and a connection terminal part including a plurality of electrodes that are electrically connected to the sensing part and to which a specific voltage is applied when the components of the liquid sample are measured. The connection part makes a contact with the electrodes of the connection terminal part of the sensor and applies a specific voltage. The connection part holder holds the connection part so that the connection part protrudes toward the connection terminal part of the sensor, has an opposing surface that is disposed opposite the connection terminal part of the sensor, and forms a non-capillary space between the opposing surface and the connection terminal part of the sensor to allow communication with a space facing the adjacent electrodes of the connection terminal part of the sensor.

Advantageous Effects

With the sensor unit of the present invention, the occurrence of leakage current due to condensation can be effectively suppressed even when the device used in an environment of high temperature and high humidity.

DESCRIPTION OF EMBODIMENTS

The cell culture analyzing device1provided with a sensor unit28according to an embodiment of the present invention will now be described with reference toFIGS.1to26.

General Description of Cell Culture Analyzing Device1

The cell culture analyzing device1electrochemically senses the concentration of a specific component (such as glucose or lactic acid) contained in the culture medium (liquid sample) X (seeFIG.9) filling a well plate25(seeFIG.7) including a plurality of wells (culture containers)25a,in a state in which a sensor30(seeFIG.8, etc.) is partially immersed in the culture medium X, and analyzes the culture state. As shown inFIG.1, the cell culture analyzing device1includes an analysis unit2, a culture incubator3in whose internal space the analysis unit2is placed, and a control unit4that controls the analysis unit2and displays the analysis result. The analysis unit2and the control unit4are connected by an electric cable5.

A transparent door3athat is attached to the front of the culture incubator3is opened and the analysis unit2is placed in the internal space. The control unit4connected to the analysis unit2via the electric cable5is disposed outside the culture incubator3.

This allows the user to analyze the culture state inside the culture incubator3with the control unit4without having to open and close the door3aof the culture incubator3, which prevents contamination of the air inside the culture incubator3.

The analysis unit2is designed to be short in the horizontal (width) direction, low in the height direction, and long in the depth direction so that a plurality of analysis units2can be installed in the culture incubator3.

As shown inFIGS.2and3, the analysis unit2includes a sensor-equipped culture module20, a main body21, a drawer22, and a lifting mechanism23.

As shown inFIG.1, the main body21is disposed in the culture incubator3in advance, and is connected to the control unit4by the electric cable5. During cell culture analysis, the assembled sensor-equipped culture module20is placed in the main body21inside the culture incubator3by the user as shown inFIG.3.

The analysis unit2is configured such that in a state in which the sensor-equipped culture module20has been pulled into the main body21by the drawer22, this module can be lifted by the lifting mechanism23toward a probe holder (connection part holder)10(discussed below).

As shown inFIG.4, the sensor-equipped culture module20is assembled inside a safety cabinet C1under a room temperature environment (such as a temperature of 25° C.) after the well plate25has been filled with culture medium X (seeFIG.9) and seeded with cells. The assembled sensor-equipped culture module20is placed in the analysis unit2inside the culture incubator3, which is held at an environment of high temperature and high humidity (37° C. and a humidity of at least 90%). That is, the assembled sensor-equipped culture module20is moved from a room temperature environment to an environment of high temperature and high humidity (such as a temperature of 37° C. and a humidity of at least 90%).

The configuration for suppressing the occurrence of current leakage attributable to condensation that occurs when the sensor-equipped culture module20is moved from a room temperature environment to an environment of high temperature and humidity will be described in detail below.

As shown inFIGS.5A and5B, the lifting mechanism23includes a mounting base23adisposed inside the main body21, and a link mechanism formed by linking a plurality of arms23b,23c,23d,and23e.

The sensor-equipped culture module20that has been pulled into the internal space of the main body21by the drawer22, which can move from the main body21into the external space, is placed on the mounting base23a,and the mounting base23amoves up and down when the link mechanism is driven.

More specifically, with the lifting mechanism23, when the arm23cis driven counterclockwise in the drawing by a drive unit (not shown), the right end of the arm23blinked via the arm23dlinked to the other end of the arm23c,one end of which serves as the rotation center, is pushed down. At this point, the left end of the arm23bis linked to the side surface of the mounting base23a.

Consequently, the right end of the arm23bis pushed down around the rotation center23ba,and the left end is pushed up, which allows the mounting base23aon which the sensor-equipped culture module20is placed to be lifted upward.

At this point, a probe holder10having a probe (connection part)10a(discussed below) protruding downward is provided in the upper space in which the sensor-equipped culture module20has been raised in the analysis unit2.

This allows the lifting mechanism23to lift the sensor-equipped culture module20so that the probe10acomes into contact with the electrode31cof the sensor30included in the sensor-equipped culture module20.

As shown inFIG.6, the sensor-equipped culture module20is configured such that an adaptor bottom24, a well plate25, an adaptor top26, a bottom plate27, a sensor30, and a top plate29are disposed in that order, starting from the bottom.

The adaptor bottom24is connected to the adaptor top26via a hinge portion24a,and the well plate25is sandwiched between the adaptor bottom24and the adaptor top26.

As shown inFIG.7, the well plate25is configured to include a total of 24 wells (culture containers)25ain four vertical rows and six horizontal rows. There are several types of well plate25, including general-purpose plates, and the adaptor bottom24and the adaptor top26are selected to suit the type of well plate25.

As described above, the adaptor top26is attached to the adaptor bottom24via the hinge portion24aso as to be openable and closable. The adaptor top26has through-holes41aprovided to line up with the positions of the plurality of wells25aincluded in the well plate25, and positioning through-holes41bprovided at the four corners of the flat plate.

The through-holes41aare provided in four vertical rows and six horizontal rows to line up with the positions of the 24 wells25aincluded in the well plate25. The sensors30are immersed in the culture medium X in the wells25athrough the through-holes41a.

The legs40of the bottom plate27to which the sensors30are attached are inserted into the through-holes41b,and this positions the sensors30relative to the wells25a.

The bottom plate27is disposed over the top surface of the adaptor top26in a state in which the plurality of sensors30are attached to the top surface (first surface) of the bottom plate27.

The sensors30are configured, for example, by sputtering a carbon electrode layer onto the upper surface of a PET (polyethylene terephthalate) film, which is a resin material. As shown inFIG.8, the sensors30each have a main body31, a sensing part31a,a connection terminal part31b,a bent portion32, and a linking portion33.

The main body31is a substantially rectangular flat member, and is linked at its upper end portion to the bent portion32.

As shown inFIG.9, the sensing part31ais provided on the surface of a wide portion at the lower end of the downwardly facing, substantially T-shaped main body31, and includes measurement electrodes (a working electrode, a counter electrode, and a reference electrode). The sensing part31ais immersed in the culture medium X contained in the well25a,and a specific voltage is applied to the measurement electrodes, the result being that the concentration of a specific component (such as glucose or lactic acid) contained in the culture medium X is electrochemically measured.

The measurement electrodes included in the sensing part31aare formed by applying an electrode layer by vapor deposition with a laser and then dividing the electrodes. The measurement electrodes may have an electrode pattern formed by screen printing in order to improve insulation between wirings.

Here, when the concentration of glucose contained in the culture medium X is measured, the reagent layer immobilized on the surface of the working electrode may contain, as a glucose oxidizing enzyme, glucose oxidase (GOx) or glucose dehydrogenase (GDH), as well as a redox mediator, for example.

The glucose concentration is measured as follows. The glucose that has permeated from the culture medium X through the protective membrane is oxidized in a reaction with the enzyme (such as, GOx or GDH) in the reagent layer and becomes gluconolactone, and the electrons generated by the oxidation reaction of hydrogen peroxide or the reduced form of the redox mediator produced at the same time is converted into a current value.

As shown inFIG.8, the bent portion32is the portion that links the main body31and the linking portion33, and is bent at a substantially right angle along a specific bending line. Consequently, the linking portion33is disposed at a substantially right angle to the main body31.

As shown inFIG.8, the linking portion33links the upper ends of the main bodies31of the four sensors30disposed in the horizontal direction to each other via the bent portions32.

A connection terminal part31bhas four electrodes31cdisposed in a set of four, corresponding to the measurement electrodes of the sensing part31aof one sensor30. The four electrodes31care electrically connected to the measurement electrodes (working electrode, counter electrode, and reference electrode) included in the sensing part31adisposed at the lower portion of the main body31of the sensor30.

As shown inFIG.8, the plurality of sensors30included in the sensor unit28of this embodiment each include the main body31, the sensing part31athat is disposed on the lower end side of the main body31and is immersed in the culture medium X to measure a component of the culture medium X, and the linking portion33that connects a plurality of sensors30to each other on the upper end side of the main body31.

Consequently, the sensors30are attached to the upper surface of the bottom plate27in a state of being linked together by the linking portions33, so the positions of the sensors30that are linked together can be accurately determined.

Consequently, the sensors30can be positioned (position, angle, etc.) more accurately with respect to the plurality of wells (culture containers)25aincluded in the well plate25.

As a result, the sensors30are immersed at a more or less consistent depth in the culture medium X filling the wells25a,which affords more stable measurement results.

As shown inFIGS.6and10, the top plate29is disposed so as to cover the upper surface of the sensors30attached to the upper surface of the bottom plate27. The top plate29has pressing portions29athat press the upper side of the bent portions32of the sensors30downward, and through-holes29b.

As shown inFIG.10, the sensors30are disposed so as to be sandwiched between the upper surface of the bottom plate27and the lower surface of the top plate29, in a state in which the linking portions33are bent.

At this time, each sensor30is held between a support portion27bon the bottom plate27side and the pressing portion29aon the top plate29side, as shown inFIG.10.

That is, the support portion27bthat supports the lower side of the bent portion32of the sensor30is provided at the opening edge of a through-hole27ain the bottom plate27. The pressing portion29athat presses the upper side of the bent portion32of the sensor30downward is provided at the portion of the top plate29that is opposite the support portion27b.

Consequently, the upper surface of the sensor30is supported by the pressing portion29aprovided on the lower surface side of the top plate29, and the lower surface of the sensor30is supported by the support portion27bprovided on the upper surface side of the bottom plate27.

The support portion27bhas an upper surface curved portion shape including a curved surface on the upper surface as shown inFIG.10. The pressing portion29ahas a lower surface curved portion shape including a curved surface on the lower surface as shown inFIG.10.

Consequently, when the sensor30is sandwiched between the top plate29and the bottom plate27as shown inFIG.10, the bent portion32of the sensor30is held in a state of being sandwiched between the support portion27band the pressing portion29a.

The bent angle of the sensor30is therefore accurately defined, so the sensing part31aprovided at the lower end of the main body31of the sensor30is positioned in a stable state. Structure for Suppressing Leakage Current due to Moisture Produced by Condensation

Here, as discussed above, a configuration for suppressing the occurrence of leakage current caused by condensation that occurs when the sensor-equipped culture module20is brought from a room temperature environment to an environment of high temperature and humidity will be described.

That is, when the sensor-equipped culture module20assembled at room temperature (such as 25° C.) is placed in the analysis unit2inside the culture incubator3maintained at an environment of high temperature and high humidity (37° C., humidity of at least 90%), the surface of the sensor30, which is close to room temperature, is lower than the temperature inside the culture incubator3, and condensation may occur on the surface of the sensor30(seeFIGS.17A and17B). If the electrodes31cof the sensor30are connected by condensation, there is the risk that a current leak will occur, making it impossible to make measurements using a very small current (cell culture analysis) properly.

In view of this, the cell culture analyzing device1of this embodiment suppresses the occurrence of leak current with the following configuration.

That is, as shown inFIGS.6and8, in the sensor-equipped culture module20, the top plate29has a plurality of the through-holes29bprovided to line up with the positions of the connection terminal parts31bof the sensors30, as mentioned above.

As shown inFIG.11, the connection terminal parts31bof the sensors30attached to the upper surface of the bottom plate27are disposed in the through-holes29bso as to be exposed when viewed from the upper surface side of the top plate29. That is, the connection terminal parts31bare disposed at the bottom portions of the through-holes29b.

As shown inFIGS.15and16, voltage is applied in a state in which the distal ends of the above-mentioned probes10aare in contact with the electrodes31cconstituting the connection terminal parts31bvia the through-holes29bin the top plate29, and the culture medium X is measured by the measurement electrodes electrically connected to the electrodes31cof the connection terminal parts31b.

The probes10ainserted into the through-holes29bare held by the probe holder10, which is made of resin, for example. As shown inFIG.12, the probe holder10is integrated with a metal plate12and in this state is provided so that the plurality of probes10aprotrude from the metal plate12.

As shown inFIG.13, the probe holder10has a metal plate12attached to its lower surface, and has on its upper surface a box-shaped probe box10bthat is open at the top.

A board11to which the plurality of probes10aare soldered is disposed on the bottom surface of the probe box10b.That is, the probes10aprotrude from the bottom surface of the probe box10bas shown inFIG.14, and are electrically connected to the board11by being soldered in a state in which the board11is set on the bottom surface of the probe box10b(see the portions in dashed circles inFIG.16).

The upper and lower surfaces of the board11may be molded from resin to make them resistant to water and moisture (see the dots portions inFIG.16).

When the probe holder10is placed on the upper surface of the top plate29in a state in which the probes10ahave been soldered to the board11, the distal ends of the probes10acome into contact with the electrodes31cincluded in the connection terminal parts31bof the sensors30, as shown inFIG.15.

That is, when the probe holder10holding the probes10ain a state of protruding downward is disposed on the upper surface of the top plate29, as shown inFIG.16, the probes10aare inserted into the through-holes29bin the top plate29and make contact with the electrodes31cconstituting the connection terminal parts31bof the sensors30disposed at the bottom portions of the through-holes29b.

The probes10aare biased downward by a spring (not shown), and move upward upon contact with the electrodes31c,so their contact state with the electrodes31cis maintained.

As shown inFIG.16, a specific space S1is formed between the upper surface of the top plate29and the lower surface (metal plate12) of the probe holder10. The top plate29is provided with the through-holes29bthat connect the specific space S1side with the bottom plate27side. Consequently, the connection terminal parts31bof the sensors30are exposed in the specific space S1on the bottom plate27via the through-holes29b.

Only the probes10aprotruding downward from the probe holder10are in the space S1formed between the upper surface of the top plate29and the lower surface of the probe holder10.

Here, the space S1is formed so that its height is greater than the thickness of the top plate29, for example.

Consequently, open spaces S1are formed above the electrodes31cconstituting the connection terminal parts31bto which voltage is applied via the probes10a.

This means that even if condensation should occur on the surface of the sensor-equipped culture module20when the module is moved from a room temperature environment to the culture incubator3having an environment of high temperature and humidity, air permeability can be ensured by the open spaces S1. Accordingly, the vicinity of the connection terminal part31bmore readily adapts to the environment of high temperature and humidity, good ventilation makes it less likely that the condensed moisture will grow, and therefore it is less likely that adjacent electrodes31cwill be electrically connected by condensation.

As a result, leakage current is less likely to be caused by condensation that occurs when the sensor-equipped culture module20is moved from a room temperature environment to an environment of high temperature and high humidity, so more accurate measurement can be performed.

Also, with the configuration of this embodiment, the probe holder10has small diameter portions10c,which have a smaller outside diameter than the upper portions, at the portions where the vicinity of the distal ends of the multiple probes10aare held.

This minimizes the volume of the distal end portion of the probe holder10in the spaces S1above the electrodes31cconstituting the connection terminal parts31bwith which the distal ends of the probes10amake contact, and ensures the spaces S1can be as large as possible.

This prevents the growth of moisture condensed around the electrodes31cconstituting the connection terminal parts31bof the sensors30, and effectively suppresses the occurrence of leakage current.

Furthermore, in this embodiment, the through-holes29bin the top plate29into which the probes10aare inserted are formed so as to communicate with the space above two adjacent electrodes31c.That is, the through-holes29bare formed so that one hole covers the range of two of the electrodes31c.

Consequently, the spaces S1formed above the electrodes31care opened up wider, making it possible to effectively suppress the growth of moisture condensed on the electrode surface where the electrodes31care disposed.

As shown inFIG.17A, the electrodes31cconstituting the connection terminal parts31bof the sensors30are provided such that the distance L between the electrodes31cis greater than the width W of each electrode31c.

This increases the distance between the electrodes31cand makes it less likely that a water film formed by condensed moisture will electrically connect the electrodes31c,which prevents leakage current from flowing between the electrodes31c.

Furthermore, a water-repellent resist (water-repellent layer)35is provided on the surface of the base material34(PET sheet) of the sensors30.

As shown inFIG.17B, the moisture condensed on the electrode surfaces of the sensors30turns into spherical water droplets W1due to the water repellency of the water-repellent resist35. This effectively prevents the water droplets W1from joining together between the electrodes31cand forming a water film, which would otherwise allow leakage current to flow.

Furthermore, the water-repellent resist35is formed so that its thickness is greater than the thickness of the electrodes31c.

This extends the creepage distance between the electrodes31cand more effectively suppresses the occurrence of leakage current between the electrodes31c.

Also, since the surfaces of the electrodes31care located lower than the water-repellent resist35, it is less likely that the moisture condensed on the surface of the electrodes31cwill join up with the moisture condensed on the surface of the water-repellent resist35.

Furthermore, the water-repellent resist35is provided with convex portions35athat protrude upward at the edge portions adjacent to the outer periphery of the electrodes31c.

Consequently, moisture condensed on the surface of the water-repellent resist35collects on the surface of the water-repellent resist, making it less likely that the moisture will join up on the electrode31cside.

The convex portions35aformed at the edge portions of the water-repellent resist35may be formed, for example, as shown inFIG.18, by making use of a step formed in a cutout cross section when the water-repellent resist35formed on a base52is punched out using a pinnacle (common name)51.

Alternatively, the convex portions35aof the water-repellent resist35may be formed by screen printing while pressing a plate54against the upper surface of a form53as shown inFIG.19Bin a state in which a resist material R1has been put into the form53placed on a base55as shown inFIG.19A.

In this case, as shown inFIG.19B, when the form53is lifted up from the base55, the protruding portion formed at the end of the water-repellent resist35due to the saddle phenomenon may be used as the convex portion35a.

The thicker is the water-repellent resist35, the more the ends of the protruding portion will naturally rise up due to the saddle phenomenon, so these raised portions can be utilized as the convex portions35a.

Main Features

In order to suppress the occurrence of leakage current due to condensation and perform analysis properly, the sensor unit28of this embodiment includes the sensors30, the bottom plate27, the top plate29, and the probe holder10, as shown inFIG.16. The sensors30have the connection terminal parts31bincluding a plurality of electrodes31cthat are electrically connected to the sensing parts31aand to which a specific voltage is applied when measuring a component of the culture medium X. The bottom plate27has an upper surface to which the connection terminal parts31bare attached and a lower surface that is on the opposite side form the upper surface. The top plate29has the through-holes29binto which are inserted the probes10athat make contact with the electrodes31cand apply a specific voltage, and is disposed so as to sandwich the connection terminal parts31balong with the bottom plate27. The probe holder10holds the probes10aso that the probes10aprotrude toward the connection terminal parts31b,has the metal plate12disposed opposite the connection terminal parts31bof the sensors30, and is disposed so that the specific spaces S1are formed between the lower surface of the metal plate12and the top plate29.

Consequently, condensation occurs on the surface of the sensor unit28that has been placed in a room temperature environment or an environment of high temperature and humidity, but the specific spaces S1are formed at the portions opposite the connection terminal parts31bincluding the plurality of electrodes31c.Accordingly, as shown inFIG.20A, it is less likely that the moisture (water droplets W1) condensed on the surface of the sensor30will grow to the point of electrically connecting the electrodes31c.

Consequently, even when the device is used in an environment of high temperature and high humidity, as shown inFIG.20B, the moisture condensed between the electrodes31cforms a water film W2, which effectively suppresses leakage current, and this allows various kinds of measurement related to cell culture analysis to be performed very accurately.

The main components of the sensor unit28in this embodiment will now be described in further detail.

FIG.21Ais a cross-sectional view of the sensor unit28immediately before used sensors30are replaced.

The sensor unit28of this embodiment is a device constituting part of the cell culture analyzing device1that is disposed inside the culture incubator3. The sensor unit28is configured to include a disposable part (the members below the dashed line inFIG.21A) and a reusable part (the members above the dashed line inFIG.21A).

The cell culture analyzing device1estimates the cell culture state by measuring metabolic components of the culture medium with the sensor unit28while culturing the target cells in a culture medium in a plurality of wells (culture containers)25ain the culture incubator3. When replacing the target cells, the wells (culture containers)25aand the sensors30of the sensor unit28are the primary portions that are replaced, and the other connection parts electrically connected to the sensors30(the members above the dashed line in the drawing) are reused.

The disposable part (below the dashed line in the drawing) mainly includes the sensors30, the culture medium60(as a liquid sample) in which the sensing parts31aof the sensors30are immersed for measurement, and the wells (culture containers)25afor holding this culture medium.

The reusable portion (above the dashed line in the drawing) mainly includes the probes (connection parts)10athat directly make contact with the electrodes31cof the connection terminal parts31bof the sensors30, and the probe holder (connection part holder)10.

Here, the disposable part and the reusable part are configured to be detachable, and the user replaces the disposable part inside the culture incubator3.

As discussed above, the inside of the culture incubator3is an environment of high temperature and high humidity (37° C., humidity 90%). In replacing the disposable part in such an environment of high temperature and high humidity, the disposable part is stored in a refrigerator or at room temperature immediately before use. Therefore, in the hot and humid environment of the culture incubator3, condensation is likely to occur on the disposable part due to the temperature difference between the inside of the culture incubator3and the disposable part.

Also, if the reusable part is not allowed to stand long enough to reach the internal temperature after being installed in the culture incubator3, there is a risk of condensation forming on the surface.

In particular, the probes10aincluded in the reusable part are made of a conductive metal, have a large thermal capacity, and take time to reach the temperature inside the culture incubator3, and as such are more susceptible to the adhesion of moisture. Therefore, if the reusable part is used in the culture incubator3without allowing it to stand for a sufficient time after being installed, the probes10aon which a large amount of condensation has occurred will be electrically connected to the electrodes31cwhose temperature is still close to room temperature.

As a result, after the disposable part has been replaced, moisture adhering to the reusable part and condensation caused by temperature changes in the disposable part may cause a short circuit or leakage current between electrical contacts.

If the electrical contacts between the connection terminal parts31bof the sensors30and the probes10athat make contact with the connection terminal parts31bare sealed in a waterproof structure, then any moisture adhering to the reusable part will be sealed in the waterproof structure at the time of replacement. This ends up making it more likely that a short circuit or leakage current will occur between the electrical contacts as a result of the sealed-in moisture.

In view of this, in the sensor unit28of this embodiment, the connection terminal parts31bof the sensors30, which are electrical contact portions, and the area around the probes10athat make contact with the connection terminal parts31bare more open to the atmosphere of the culture incubator3. As a result, even if condensation should occur, the moisture that is generated at that time can be dried by the air current circulating within the culture incubator3.

FIG.21Bis a cross-sectional view of the sensor unit28after the sensors30have been replaced.

As shown inFIG.21B, the sensor unit28measures a component in the culture medium60in a state in which the lower ends of the sensors30are immersed in the culture medium60(serving as a liquid sample) contained in the wells (culture containers)25a.

The configuration of the disposable part of the sensor unit28will now be described.

As shown inFIG.8, a sensor30has a main body31, sensing parts31athat are disposed on the main body31and immersed in the culture medium60, and connection terminal parts31bthat are electrically connected to the sensing parts31aand include a plurality of electrodes31c(seeFIG.11) to which a specific voltage is applied when measuring a component of the culture medium60.

Next, the configuration of the reusable portion of the sensor unit28will be described.

The probes10aapply a specific voltage to the connection terminal parts31bof the sensor30while in contact with the connection terminal parts31b.

The probe holder10holds the upper portions of the probes10aso that the probes10aprotrude toward the connection terminal parts31bof the sensor30.

The probe holder10also has an opposing surface61disposed opposite the connection terminal parts31bof the sensor30. Consequently, spaces S1are formed between the opposing surface61and the connection terminal parts31bof the sensor30, which communicate with the spaces faced by the adjacent electrodes31cof the connection terminal parts31bof the sensor30.

As discussed above, the probe holder10holds the probes10aso that the probes10aprotrude toward the connection terminal parts31b.Consequently, a specific height is formed between the opposing surface61and the connection terminal parts31bof the sensor30, and the spaces S1become non-capillary spaces in which capillary action does not work on the liquid near the spaces S1.

Since the spaces S1are non-capillary spaces, moisture is not absorbed between the opposing surface61and the connection terminal parts31bof the sensor30. This prevents excess moisture from entering around the connection terminal parts31bthrough capillary action.

In the cell culture analyzing device1, the spaces S1are configured to be spaces that are open to the outside of the device in a substantially horizontal direction. This causes the circulating air current inside the culture incubator3to be generated in the spaces S1as well. Consequently, the spaces S1connect the spaces faced by the adjacent electrodes31cof the connection terminal parts31bof the sensor30in a substantially horizontal direction, so any moisture produced around the electrodes31ccan be evaporated and dried. As a result, short circuits between electrical contacts and leakage current can be effectively prevented.

FIG.22is an oblique view of the probes10aand the probe holder10, in a state in which the probes10aare facing upward.

Here, the connection terminal parts31bon the sensor30side where the probes10amake contact is provided with four electrodes31cfor each sensor30.

Similarly, as shown inFIG.22, the probes10aeach have four electrodes, and are arranged in four rows in the X direction and six in the Y direction.

The adjacent probes10aare provided in spaces that communicate with each other. Also, the probes10aare provided in spaces that are open to the outside of the device so that circulating air can easily flow in the directions indicated by the arrows in the X and Y directions inFIG.22(that is, the substantially horizontal direction of the device when in use state).

As a result, in the spaces S1, the spaces facing the adjacent electrodes31cincluded in the connection terminal parts31bof the sensor30, and the adjacent probes10aof the probe holder10communicate with each other. Consequently, any moisture generated around the electrodes31cand the corresponding probes10acan be evaporated and dried, and the occurrence of short circuits and leakage current between electrical contacts can be effectively prevented.

FIG.23is a cross-sectional view of the state when the sensors30and the probe holder10have been set on the well plate25.

As shown inFIG.23, the probes10acan be directly seen from the side of the device, that is, the spaces S1form a passageway for the circulating air current in the culture incubator3because they are spaces that are open in the substantially horizontal direction of the device when in use state.

Furthermore, any moisture generated around the electrodes31cand the corresponding probes10aprovided in the spaces communicating within the spaces S1is effectively evaporated and dried by the circulating airflow. As a result, short circuits and leakage current between electrical contacts can be effectively prevented.

FIG.24Ais an oblique view of a connection terminal part31bof a sensor30.

FIG.24Bis a cross-sectional view of the connection terminal part31balong the A-A′ line inFIG.24A.

As shown inFIGS.24A and24B, the electrodes31cincluded in the connection terminal part31bare disposed so that the distance between adjacent electrodes31cis greater than the width of the electrodes31c.

Also, the water-repellent resist35is located between the electrodes31c,and the electrode31cportion is located lower than the portion of the water-repellent resist35between the electrodes31c.Consequently, the electrodes31care disposed in recesses formed in the base material34, and the portion of the water-repellent resist35between the electrodes31cis formed as a convex portion of the base material34.

That is, the length of the water-repellent resist35in the substantially horizontal direction is greater than the length of the electrode31cin the substantially horizontal direction, and the thickness of the water-repellent resist35is greater than the thickness of the electrodes31c.

This causes any moisture generated by condensation to accumulate in the recesses of the base material34in which the electrodes31care provided, effectively preventing the occurrence of short circuits or leakage current between the electrodes31c.Also, since the length of the water-repellent resist35in the substantially horizontal direction is greater than the length of the electrodes31cin the substantially horizontal direction, a sufficient distance is ensured between the electrodes31c,effectively preventing the occurrence of short circuits or leakage current between the electrodes31c.

FIG.25Ashows a detail cross-sectional view of the sensor unit28immediately before replacement of the used sensors30.

Sodium, potassium, chlorine, and the like adhere to the probes10aover long-term use. Therefore, condensed water W3, in which an electrolyte component is dissolved and through which leakage current easily flows, clings to the probes10a.This condensed water W3also clings to the connection terminal parts31bof the sensor30below.

Here, the probes10aare biased downward in the drawing by a spring or other such elastic member, and upon making contact with the electrodes31c,slide inside the probe holder10. Consequently, even if the positions of the multiple electrodes31cvary in the height direction, the probes10acan absorb this positional variance, allowing a stable electrical connection to be achieved.

On the other hand, when the probes10aand the electrodes31care electrically connected, the probes10aslide into the small diameter portion10cof the probe holder10, so that the condensed water W3containing electrolyte component clinging to the probes10ais scraped off by the lower end of the small diameter portion10cin the direction of the electrodes31c.

Therefore, as shown inFIG.25B, in a state in which the probes10aand the electrodes31care electrically connected (in the sensor unit28after the sensors30have been replaced), the condensation water droplets W3adhering to the probes10aare scraped off by the lower end of the small diameter portion10c,and condense on the electrodes31cinto droplets.

As shown inFIG.25B, the diameter of the distal end of the probe10athat makes contact with the electrode31cis smaller than the size of the electrode31cin the radial direction.

Consequently, the condensed water W3produced by the above-mentioned sliding action can be held within the recesses in which the electrodes31care provided, which effectively prevents the occurrence of short circuits or leakage current between the electrodes31cdue to condensation.

Also, as discussed above, the probe holder10has the small diameter portion10c,whose outside diameter where the probes10aare held is smaller than the upper end (second end) side on the opposite side from the lower end, at the lower end (first end) on the electrode31cside in the portion for holding the probes10a.

This allows a gap63to be formed between the small diameter portion10cand the electrodes31c.As a result, even if there is a large amount of condensed water W3, a large amount of water can be held in the gap63by the strong adsorptive force of the meniscus (liquid bridge) generated in the gap63. This effectively prevents the occurrence of short circuits or leakage current between the electrodes31c.

FIG.25Cis a detail view of the distal end of a probe10a.

The probe10ahas a crown shape including a plurality of sharp protrusions10aaat its distal end. Consequently, the sharp protrusions10aapenetrate the oxide film formed on the surface of the electrode31cor the probe10a,which ensures electrical connection between the electrode31cand the probe10a.

Furthermore, the occurrence of poor electrical connection, which can happen when dust (loose fibers) adhering to the probes10athrough long-term use becomes embedded, can be effectively prevented, for example.

Also, even if the electrodes31care made of a material that is easily transferred, such as carbon or solder, the self-cleaning effect will prevent the accumulation of such materials on the distal ends of the probes10a.

Here, the probes10aare preferably made of a highly corrosion-resistant material such as an SUS alloy, a palladium alloy, palladium, rhodium, iridium, tungsten, or titanium, all of which are resistant to corrosion by moisture.

This allows highly reliable electrical connection to be performed even when the electrical connection is made in an environment of high temperature and high humidity inside the culture incubator3where poor contacts may result.

FIG.26is a graph of the relation between the elapsed time during replacement of the disposable sensors30and the temperature of the disposable parts including the sensors30.

After the sensors30are replaced with new ones, condensation occurs on the surface of the disposable part including the new sensors30while the temperature of this part gradually approaches the temperature inside the culture incubator3, which is a high-temperature and high-humidity environment, until the dewpoint temperature is finally reached. During this process, as discussed above, moisture such as the condensed water W3is actively drawn into the recesses in which the electrodes31cof the connection terminal parts31bare provided.

Then, after the disposable part including the sensors30has reached the temperature inside the culture incubator3, as mentioned above, the moisture in the spaces S1open to the outside is evaporated and dried by the circulating airflow that is formed in the culture incubator3in a substantially horizontal direction.

Consequently, moisture such as the condensation water W3generated in the spaces S1grows up until the sensor unit28reaches the dewpoint temperature, but once the dewpoint temperature is reached, the circulating airflow generated within the culture incubator3can evaporate and dry the generated condensation water, etc.

As a result, the occurrence of short circuits or leakage current between the electrodes31cdisposed in the spaces S1can be effectively prevented.

As described above, with the sensor unit28in this embodiment, after the sensors30have been replaced, the above-mentioned two-stage technique (the holding of the condensation water W3, and its evaporation and drying) can effectively prevent the occurrence of short circuits or leakage current between the electrodes31c.

Other Embodiments

An embodiment of the present invention was described above, but the present invention is not limited to or by the above embodiment, and various modifications are possible without departing from the gist of the invention.(A)

In the above embodiment, an example was given in which the water-repellent resist35was formed on the electrode surface on which the plurality of electrodes31cconstituting the connection terminal parts31bof the sensors30were arranged. However, the present invention is not limited to this.

For example, the configuration may be such that the electrode surface on which the connection terminal parts are provided has no water-repellent layer.

Nevertheless, as described in the above embodiment, a configuration in which a water-repellent layer is provided on the electrode surface is preferable because condensed moisture will be less prone to changing into droplets and forming a water film.(B)

In the above embodiment, an example was given in which the through-holes29bin the top plate29into which the probe10awas inserted were formed so as to communicate with the space above two adjacent electrodes31c.However, the present invention is not limited to this.

For example, the through-holes in the top plate may be provided one for each electrode, or one for three or more electrodes.(C)

In the above embodiment, an example was given in which the upper ends of four sensors30were linked by a linking portion33so that the four sensors30formed a set. However, the present invention is not limited to this.

For example, the number of sensors linked by the linking portion may be three or fewer, or may be five or more.

In any case, the positions of the mutually linked sensors will be accurately defined, so the positional accuracy of the sensors can be improved.(D)

In the above embodiment, an example was given in which the sensors30were used in a state of having been bent at the bent portions32. However, the present invention is not limited to this.

For example, the configuration may be such that the sensors are used without being bent.

Here again, configuring the sensors to be linked by linking portions at the upper end portions of the main bodies of the sensors provides the same effect as above, that of improving the positional accuracy of the sensors.(E)

In the above embodiment, an example was given in which the sensors30had a substantially inverted T shape, but the present invention is not limited to this.

For example, a sensor that is substantially I-shaped or substantially L-shape may be used instead.(F)

In the above embodiment, an example was given in which the sensor-equipped culture module20placed in a room temperature (25° C.) environment was put under an environment of high temperature and high humidity (37° C., a humidity of at least 90%) in the culture incubator3. However, the present invention is not limited to this.

For example, the environment to which the sensor module is placed before being put in a high-temperature environment is not limited to one of room temperature, and may be any environment suitable for a pre-culture treatment of the sensor module.

Alternatively, the same effect as above can be obtained when a sensor module that has been pretreated at a temperature lower than room temperature is placed in an environment of room temperature, or of a temperature and humidity higher than room temperature.

INDUSTRIAL APPLICABILITY

The sensor unit of the present invention exhibits the effect that the occurrence of leakage current attributable to condensation can be effectively suppressed even when used in an environment of high temperature and high humidity, and is therefore widely applicable to a variety of sensor units used in cell culture analysis.

REFERENCE SIGNS LIST