Observation device body, cell culture vessel and cell observation device
The cell observation device with a removable cell culture vessel and magnetic connection ensures continuous observation and cost-effective data acquisition, addressing reproducibility and cost issues in existing technologies.
Patent Information
- Application Number
- JP2024089433
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- Filing Date
- 2024-05-31
- Publication Date
- 2025-12-11
AI Technical Summary
Existing cell observation devices require cells to be transferred from a culture environment to a microscope for observation, causing temperature and shock-induced changes, leading to loss of reproducibility and high costs due to the need for new devices after each use.
A cell observation device with a removable cell culture vessel that integrates a detection element and connection terminal, allowing continuous observation and data acquisition within a cell culture device, using magnetic attraction for secure connection and vertical placement to prevent spills and shocks.
Enables accurate, reproducible, and cost-effective cell observation by maintaining consistent conditions and allowing reuse of the observation device with the cell culture vessel.
Smart Images

Figure 2025181447000001_ABST
Abstract
Description
[Technical Field]
[0001] The present disclosure relates to an observation device body, a cell culture vessel, and a cell observation device. [Background technology]
[0002] Prior art cell observation devices are described, for example, in Patent Document 1 and Non-Patent Document 1. These prior art devices propose devices equipped with a sensor at the bottom of a cell culture vessel as devices for observing cells during culture. [Prior art documents] [Patent documents]
[0003] [Patent Document 1] Patent No. 6803164 [Non-Patent Document 1] K. Imai et al., A lens-free single-shot fluorescent imaging system using CMOS image sensors with dielectric multi-layer filter, 2017 19th International Conference on Solid-State Sensors, Actuators and Microsystems (TRANSDUCERS), Kaohsiung, Taiwan, 2017, pp. 139-142, doi:10.1109 / TRANSDUCERS.2017.7994007. Summary of the Invention [Problem to be solved by the invention]
[0004] In the prior art described in Patent Document 1 and Non-Patent Document 1, cell culture is performed by placing a dish or well in a cell culture device (also called an incubator), and then the dish or well is removed from the culture environment and observed under a microscope, which does not allow for continuous observation. In this case, the state of the cells changes due to temperature and shock caused by movement, and the reproducibility of cell culture under the same conditions is lost. Therefore, it is difficult to obtain necessary data about cells being cultured under the same conditions.
[0005] Furthermore, a clean dish or well is required to replace the cells or culture medium to be observed. The above-mentioned prior art also describes a configuration in which a signal processing circuit for processing detected signals is integrally formed in the dish or well to enable continuous observation, but the dish or well is discarded after use, and no consideration is given to reducing the cost of replacing the cell observation device with a new one.
[0006] Therefore, there is a demand for a cell observation device that can be installed directly in a cell culture device, can acquire desired data regarding cells being cultured with high precision, and can perform cell observation at low cost with high reproducibility. [Means for solving the problem]
[0007] The observation device main body (1) 104 according to the present disclosure is an observation device main body 104 on which a cell culture vessel 103 is placed, The apparatus comprises a mounting receptacle 108 on which a cell culture vessel 103 is removably placed, a positioning part 171 on at least one side of the mounting receptacle 108 for regulating the position of the cell culture vessel 103, and a connection terminal 150 of the observation device main body 104 for receiving an output signal from the cell culture vessel 103, and the positioning part 171 is located between the connection terminal 150 of the observation device main body 104 and the mounting receptacle in a plan view.
[0008] Further, the cell culture vessel (2) 103 according to the present disclosure is a cell culture vessel 103 to be placed on an observation device main body 104, The observation device comprises a bottom substrate 110 including a detection element 6 for detecting the characteristics of cells and culture media, a connection terminal 115 of a cell culture vessel 103 for outputting an output signal from the detection element 6 to the outside, and a support 132 for mounting the bottom substrate 110 on the upper side, and the support 132 is fixed to the observation device main body 104 by magnetic attraction.
[0009] Furthermore, the cell observation device 100 according to the present disclosure is a cell observation device in which the cell culture vessel 103 described in (2) is mounted on the observation device main body 104 described in (1), A connection terminal 150 of the observation device main body 104 and a connection terminal 115 of the cell culture vessel 103 are connected, and the support 132 is fixed to the observation device main body 104 by magnetic attraction. [Effects of the Invention]
[0010] According to the cell observation device 100 of the present disclosure, the cell culture container 103 is placed on the observation device main body 104 and installed inside the cell culture device 100, and desired data regarding the cells being cultured can be obtained with high accuracy, enabling cell observation to be performed at low cost and with high reproducibility.
[0011] The observation device main body 104 of the present disclosure is equipped with a mounting receiving portion 108 on which the cell culture vessel 103 is detachably placed, a positioning portion 171 on at least one side of the mounting receiving portion 108 that regulates the position of the cell culture vessel 103, and a connection terminal 150 of the observation device main body 104 that receives an output signal from the cell culture vessel 103.Therefore, even if the cell culture vessel 103 is replaced, the connection terminal 150 is always positioned in the correct position, and the data output signal can be properly acquired.
[0012] Furthermore, the cell culture vessel 103 of the present disclosure comprises a bottom substrate 110 including a detection element 6 that detects the characteristics of cells and culture medium, a connection terminal 115 of the cell culture vessel 103 that outputs an output signal from the detection element 6 to the outside, and a support 132 that mounts the bottom substrate 110 on the upper side, and since the support 132 is fixed to the observation device main body 104 by magnetic attraction, the connection between the connection terminals 115 and 150 can be maintained good even if the cell culture vessel 103 is replaced.
[0013] Furthermore, in the cell observation device 100 of the present disclosure, the connection terminal 150 of the observation device main body 104 is connected to the connection terminal 115 of the cell culture vessel 103, and the support 132 is fixed to the observation device main body 104 by magnetic attraction, so even if the cell culture vessel 103 after use is replaced or discarded for cleaning, the observation device main body 104 can be repeatedly used in common for multiple cell culture vessels 103. Therefore, a cell observation device 100 is realized that can acquire data with high accuracy and perform cell observation with high reproducibility at low cost.
[0014] The cell culture vessel 103 can be placed on the observation device main body 104 so that it can be removed vertically. This prevents lateral impacts on the cell culture vessel 103, which can prevent the cells and culture medium in the storage space 109 of the well member 101 from spilling out. [Brief explanation of the drawings]
[0015] [Figure 1] 1 is a perspective view showing the appearance of a cell observation device 100 according to an embodiment of the present disclosure, as viewed obliquely from the front. [Figure 2] FIG. 2 is a perspective view showing the appearance of the cell observation device 100, as viewed from the left side of FIG. 1 at an angle from the front. [Figure 3] FIG. 1 is a perspective view of a cell culture vessel 103. [Figure 4] 3. FIG. 3 is a front view of the cell culture vessel 103 as seen from the front (upstream in the longitudinal direction Y, lower left in FIG. 3). [Figure 5A] FIG. 2 is a perspective view of a well member 101. [Figure 5B] FIG. 2 is a perspective view of a sealing material 160. [Figure 5C] FIG. 1 is a perspective view of a slide glass 191. [Figure 5D] FIG. 10 is a perspective view of adhesive layer 176. [Figure 5E] FIG. [Figure 5F] FIG. 1 is a perspective view showing an assembly 180 of a portion of a cell culture vessel 103. [Figure 5G]FIG. [Figure 5H] FIG. [Figure 6] 10 is a bottom view showing the vicinity of a connection support portion 163 of a support body 132 on a bottom substrate 110. FIG. [Figure 7] FIG. 2 is a perspective view showing the appearance of the observation device main body 104, as seen obliquely from the front. [Figure 8] 1 is a plan view showing the front part (upstream part in the longitudinal direction Y) of the observation device main body 104. FIG. [Figure 9] FIG. 9 is a cross-sectional view taken along the line IX-IX in FIG. [Figure 10] 9 in the front part of the cell observation device 100 (the upstream part in the longitudinal direction Y, the right part in FIG. 9). [Figure 11] 11 is a cross-sectional view of the observation device main body 104 taken along the cutting line XI-XI in FIG. 10 with the cell culture vessel 103 removed. [Figure 12] 12 is a cross-sectional view taken along the line XII-XII in FIG. 10. [Figure 13] 11 is an enlarged cross-sectional view showing the upward connection terminal 150 of FIG. 10. FIG. [Figure 14] 1 is a cross-sectional view of a connecting body 181, showing a state in which a wiring board 182 is unfolded, in a simplified manner for ease of understanding. [Figure 15] 15 is a plan view showing a wiring board 182 of FIG. 14 with a portion thereof omitted. [Figure 16] 15 is a bottom view showing the wiring board 182 of FIG. 14 with a portion thereof omitted. [Figure 17] 1 is a simplified plan view showing a detection region 143 provided for each storage space 109 of a well member 101. FIG. [Figure 18] 10 is a block diagram showing the electrical configuration of the detection element circuit 107 on the bottom substrate 110 and the control board 116 built into the observation device main body 104. FIG. [Figure 19] FIG. 2 is a plan view showing the configuration of a pixel 3. [Figure 20] 20 is a cross-sectional view taken along the line XXa-XXb-XXc-XXd-XXe in FIG. 19. [Figure 21] FIG. 2 is a partial plan view showing the state of observation of the bottom substrate 110 using transmitted light. [Figure 22A] FIG. 1 is a plan view showing a cell culture vessel 103 having an auxiliary observation area outside the pixel area, which is made up of an inorganic film and an organic film or an inorganic film only. [Figure 22B] FIG. 10 is a plan view showing another example of a cell culture vessel 103 having an auxiliary observation area outside the pixel area, which is made up of an inorganic film and an organic film or only an inorganic film. [Figure 23] FIG. 2 is a circuit diagram showing a configuration of a sample-and-hold circuit 112. [Figure 24] 4 is a timing chart for explaining the operation of the sample and hold circuit 112. [Figure 25A] FIG. 2 is a diagram illustrating the photodetection circuit 30 in a reset state. [Figure 25B] FIG. 2 is a diagram illustrating the photodetection circuit 30 in an exposed state. [Figure 25C] FIG. 2 is a diagram illustrating the photodetection circuit 30 in an exposure readout state. [Figure 25D] FIG. 10 is a diagram illustrating the photodetection circuit 30 in a reset readout state. [Figure 26] 4 is a timing chart for explaining the operation of the pixel circuit 111. DETAILED DESCRIPTION OF THE INVENTION
[0016] Hereinafter, embodiments of the present disclosure will be described in detail with reference to the drawings. Note that the drawings used in the following description are schematic. The dimensional ratios and the like in the drawings do not necessarily correspond to the actual ones. In the following embodiments of the present disclosure, a "detection element" sometimes given a reference symbol 6 includes configurations other than a photodiode, and when a typical example is a photodiode, it may be called a "photodiode 6" with the same reference symbol 6, but this is not intended to limit the scope of the rights.
[0017] FIG. 1 is a perspective view showing the appearance of a cell observation device 100 according to an embodiment of the present disclosure, as viewed obliquely from the front, and FIG. 2 is a perspective view of the left side of the cell observation device 100 shown in FIG. 1, as viewed obliquely from the front. The cell observation device 100 includes a cell culture vessel 103 and an observation device main body 104, which can be called a controller module. The overall shape of the cell culture vessel 103 and the observation device main body 104 is generally rectangular in plan view. This rectangle has a short side in the width direction X and a long side in the longitudinal direction Y. The cell culture vessel 103 is placed on the observation device main body 104 so as to be detachable in the up-down direction Z.
[0018] Fig. 3 is a perspective view of the cell culture vessel 103, and Fig. 4 is a front view of the cell culture vessel 103 as seen from the front (upstream in the longitudinal direction Y, lower left in Fig. 3). The cell culture vessel 103 has a well member 101 and a bottom substrate 110 provided below the well member 101.
[0019] 5A to 5H are exploded perspective views showing the components of the cell culture vessel 103. FIG. 5A is a perspective view of a well member 101. The well member 101 has one or more walls 166 (for example, in this embodiment, two columns in the width direction X and four rows in the length direction Y, for a total of eight walls) that form bottomless storage spaces 109 extending in the up-down direction Z and that accommodate and culture cells and culture media, and flanges 167 that protrude from the lower part of the wall 166 to both outer sides in the width direction X (left-right directions in FIG. 5A ), and is made of synthetic resin. A rising piece 169 having a locking recess 175 for snapping due to the elasticity of the synthetic resin is provided at the outer end of the flange 167.
[0020] Cells cultured and observed according to the embodiments of the present disclosure may be either adherent or suspension-adherent. The cell types may be, for example, animal cells, plant cells, yeast cells, or bacterial cells. The cells may be stem cells suitable for regenerative medicine. The stem cells may be pluripotent stem cells such as induced pluripotent stem cells (iPS cells) or somatic stem cells such as mesenchymal stem cells (MSCs).
[0021] 5B is a perspective view of the sealant 160, and FIG. 5C is a perspective view of the slide glass 191. The detection element circuit 107 is formed on the upper surface of the slide glass 191. The slide glass 191 on which the detection element circuit 107 is formed forms the bottom of the storage space 109 of the well member 101. The sealant 160 is removably interposed between the lower end of the wall 166 of the well member 101 and the upper surfaces of the slide glass 191 and the detection element circuit 107, and prevents leakage of cells and culture medium from each storage space 109. Examples of glass materials used for the slide glass 191 include borosilicate glass, crystallized glass, and quartz.
[0022] FIG. 5D is a perspective view of the adhesive layer 176, and FIG. 5E is a perspective view of the support 132. The adhesive layer 176 shown in FIG. 5D may be a so-called double-sided tape structure in which adhesive is applied to both sides of a synthetic resin film, and an opening 174 is formed. The support 132 shown in FIG. 5E is made of a plate of a ferromagnetic material, such as stainless steel, iron, or nickel, and has an elongated shape in the longitudinal direction Y. The support 132 has a mounting portion 162 and a connection support portion 163. The support 132 has raised portions 165 on both sides to improve rigidity and strength. The adhesive layer 176, slide glass 191, sealant 160, and well member 101 are mounted on the mounting portion 162 in this order. An opening 168 is formed in the mounting portion 162. The connection support portion 163 of the support body 132 extends forward (diagonally downward left in FIG. 5E) closer to one end in the longitudinal direction Y than the mounting portion 162.
[0023] A reinforcing piece 170 for improving rigidity is fixed to the upper part of the connection support part 163. The reinforcing piece 170 may be made of a plate of ferromagnetic material, similar to the support body 132.
[0024] FIG. 5F is a perspective view showing an assembly 180 that is a part of the cell culture vessel 103, and FIG. 5G is a perspective view of a connecting body 181. The assembly 180 is configured by combining a support 132, an adhesive layer 176 (see FIG. 5D), a slide glass 191 on which the detection element circuit 107 is formed, a reinforcing piece 170, and a connecting body 181. The connecting body 181 has a flexible wiring board 182 and a holding piece 183 made of synthetic resin. The wiring board 182 has a connecting portion 184 that is disposed on the connection support portion 163 in the front in the longitudinal direction Y (diagonally lower left in FIGS. 5F and 5G) so as to cover part of the slide glass 191 and is electrically connected to the detection element circuit 107, a curved portion 185 that is continuous with the connecting portion 184 and convex in the front in the longitudinal direction Y (lower left in FIG. 5G), and a terminal portion 186 that is continuous with the curved portion 185. A holding piece 183 that faces the connection support part 163 in the assembled state is fixed to the terminal part 186, thereby reinforcing the terminal part 186. The holding piece 183 is fixed to the lower part of the connection support part 163 with, for example, an adhesive.
[0025] FIG. 5H is a perspective view of holder 129. Holder 129 is configured symmetrically with respect to the longitudinal direction Y, is made of synthetic resin, and is manufactured by, for example, injection molding. Holder 129 has a holding portion 187 on which mounting portion 162 of support body 132 is placed and held, wall protrusions 188-190 rising from the periphery of holding portion 187, and a pair of operating portions 193, 194 that perform a snap action to attach and detach well member 101. An opening 164 is formed in holding portion 187. Wall protrusion 188 is provided at the rear (diagonally upper right in FIGS. 5E, 5F, and 5H) near the other end of holding portion 187 in the longitudinal direction Y, and is positioned by abutting against the rear end of mounting portion 162. As a result, the connection support portion 163 of the support body 132 is held by the holder 129, protruding forward (diagonally downward left in FIGS. 5E and 5H) toward one end in the longitudinal direction Y. Both sides of the connection support portion 163 in the width direction X are positioned by wall protrusions 189 and 190 extending in the longitudinal direction Y. The lower surface of the holding portion 187 of the holder 129 forms the lower surface of the bottom substrate 110 of the cell culture vessel 103.
[0026] Operating portions 193, 194 are provided on both sides of holding portion 187 in the width direction X, at midpoints in the longitudinal direction Y of wall protrusions 189, 190. Operating portion 193 has an inward-facing operating portion 197 connected to a swinging portion 196 that is angularly displaced about an axis in the longitudinal direction Y by hinge portion 195, and operating portion 197 has a locking claw 179 formed on it. By swinging knob 198 of operating portion 193 toward well member 101 by hinge portion 195, locking claw 179 of holder 129 is fitted into and hooked into locking recess 175 (Fig. 5A) of well member 101 by the elasticity of the synthetic resin, achieving a snap action that is a releasable mechanical connection. Next, conversely, by swinging the knob 198 away from the well member 101 via the hinge portion 195, the locking claws 179 of the holder 129 can be released from the locking recesses 175 of the well member 101, to which they are mechanically connected, due to the elasticity of the synthetic resin. For observation with an optical microscope, the cell culture vessel 103 is removed from the observation device main body 104, the medium in the storage space 109 is aspirated with a pipette, and then the well member 101 and sealing material 160 can be removed from the bottom substrate 110 by operating the operating portions 193 and 194. This allows cells to be observed while adjusting the distance between the slide glass 191 of the bottom substrate 110 and the objective lens barrel of an upright microscope or the like so that it is at a focal position appropriate for observation. With an inverted microscope or the like, cell observation is possible without necessarily removing the well member 101 and sealing material 160. However, if they interfere with the uniformity of the microscope's light source light, removing them allows for accurate cell observation.
[0027] Light from light source 102 (see Figures 7 and 9 described below) travels from bottom to top through opening 164 in holder 129, opening 168 formed in mounting portion 162 of support 132, and opening 174 in adhesive layer 176, passing through slide glass 191 having detection element circuit 107 and reaching storage space 109 of well member 101. This allows observation of the cells and culture medium in storage space 109. Light source 102 may be dimmed.
[0028] Examples of synthetic resin materials used for the well member 101 and the bottom substrate 110 include epoxy resin, polyimide resin, polyamide resin, acrylic resin, polycarbonate resin, etc. Examples of ceramic materials used for the well member 101 and the bottom substrate 110 include alumina (Al2O3), zirconia (ZrO2), silicon nitride (Si3N4), silicon carbide (SiC), aluminum nitride (AlN), etc.
[0029] 6 is a bottom view showing the vicinity of the connection support portion 163 of the support body 132 in the bottom substrate 110. A plurality of downward-facing connection terminals 115 (for example, in this embodiment, 24 in total, arranged in eight columns in the width direction X and three rows in the length direction Y) are formed on the terminal portion 186 of the wiring board 182 of the connector 181. The lower surface of the holding portion 187 of the holder 129 forming the lower surface of the bottom substrate 110 of the cell culture vessel 103 and the lower surface including the downward-facing connection terminals 115 are located within a single imaginary plane. This makes it easy to remove the cell culture vessel 103 upward from the observation device main body 104 and to grasp the contact and separation state between the downward-facing connection terminals 115 and the upward-downward connection terminals 150. Furthermore, for example, the cell culture vessel 103 can be moved to a flat surface and placed stably, preventing impacts on the cells and culture medium. In other embodiments, the lower surface of the holding portion 187 of the holder 129 and the lower surface including the downward connection terminal 115 do not have to be on the same imaginary plane.
[0030] 7 is a perspective view showing the appearance of the observation device main body 104 as seen obliquely from the front, and Fig. 8 is a plan view looking down from above at the front part (upstream part in the longitudinal direction Y) of the observation device main body 104. The observation device main body 104 is provided with a mounting receiver 108 that faces upward. The mounting receiver 108 is made of transparent flat glass, and its upper surface forms a horizontal mounting surface 108a. The lower surface of the holding part 187 of the holder 129, which is the lower surface of the bottom substrate 110 of the cell culture vessel 103, is placed on this mounting surface 108a.
[0031] The cell culture vessel 103 is placed on the placement receiver 108 so as to be vertically detachable. Inside the case 202 of the observation device main body 104, the light source 102 is provided below the placement receiver 108. The case 202 may be made of synthetic resin or metal.
[0032] The upper part 203 of the case 202 of the observation device main body 104 has guide parts 135 and 136 that guide both sides in the width direction X of the cell culture vessel 103 in the longitudinal direction Y. In addition, the upper part 203 of the case 202 is formed with a rear end regulating part 205 that regulates the rear end of the cell culture vessel 103 in the longitudinal direction Y.
[0033] As shown in FIG. 8, the upward connection terminals 150 are arranged in the same manner as the downward connection terminals 115 (in this embodiment, 24 terminals in total, 8 columns in the width direction X and 3 rows in the length direction Y).
[0034] 6, a pair of indicators 204 for positioning during assembly are provided on the underside of the connection support portion 163. The indicators 204 indicate, in an L-shape, the attachment positions of the corners of both side edges in the width direction X and the free end edge in the longitudinal direction Y with respect to the terminal portion 186 of the wiring board 182, in order to align the attachment positions of the holding pieces 183 (FIG. 5G, FIG. 10 described below) fixed to the underside of the connection support portion 163. Note that the number of indicators 204 is not limited to a pair, but may be one, and the shape is not limited to an L-shape, but may be a U-shape or a line. Furthermore, the indicators 204 may be formed, for example, by shallow grooves. Therefore, when the cell culture container 103 is positioned and placed on the mounting receiving portion 108 of the observation device main body 104 by the guide portion 136 and the rear end regulating portion 205, and by the stop portion 171, the downward connection terminals 115 of the terminal portion 186 individually contact the upward connection terminals 150 of the observation device main body 104.
[0035] 9 is a cross-sectional view taken along the cutting line IX-IX in FIG. 1, and FIG. 10 is an enlarged cross-sectional view of a portion of FIG. 9 at the front part (the upstream part in the longitudinal direction Y, the part on the right in FIG. 9) of the cell observation device 100. A stop portion 171 is provided between the bottom substrate 110 and the observation device main body 104 to prevent displacement of the cell culture vessel 103 in the longitudinal direction Y at a contact position where the downward connection terminal 115 and the upward connection terminal 150 come into contact with each other and to maintain that contact state. This stop portion 171 is also referred to as a positioning portion that regulates the position of the support 132. Referring mainly to FIG. 10, the stop portion 171 is formed on the upper part 203 of the case 202 of the observation device main body 104, and the protrusion 173 and the recess 172 are formed adjacent to each other. The upward connection terminal 150 is disposed in the recess 172, and the downward connection terminal 115 of the cell culture vessel 103 is located at this position. A connection terminal portion of the cell culture vessel 103 is formed by interposing a holding piece 183 between the support 132 of the cell culture vessel 103 and the downward connection terminal 115. This connection terminal portion determines the connection position between the downward connection terminal 115 and the upward connection terminal 150 by adjusting the thickness of the holding piece 183. This connection terminal portion is fitted into a recess 172 so as to be freely insertable and detachable in the vertical direction, and its position in the Y direction is regulated by a protrusion 173. By disposing and separating a stopper 171 between the connection portion of the upward connection terminal 150 and the downward connection terminal 115 and the cell culture observation portion, the position of the connection portion in the vertical and Y directions can be easily and reliably regulated.
[0036] 11 is a cross-sectional view of the observation device main body 104 from the cutting line XI-XI in FIG. 10 with the cell culture vessel 103 removed. A permanent magnet piece 133 is fixed to the lower part of the protrusion 173 within the case 202 via a spacer 206. The support 132 made of a ferromagnetic material of the cell culture vessel 103 and the permanent magnet piece 133 provided on the protrusion 173 constitute a magnetic force generator 161 that exerts a magnetic attraction force in a direction in which the downward-facing connection terminal 115 and the upward-facing connection terminal 150 approach each other. The upward-facing connection terminals 150 are arranged along the width direction X, and the permanent magnet piece 133 is formed in an elongated rectangular parallelepiped shape with its magnetic poles aligned along the width direction X. The permanent magnet piece 133 is positioned so that the magnetic attraction force in the width direction X where the downward-facing connection terminal 115 and the upward-facing connection terminal 150 are in elastic contact is uniformly distributed. The spacer 206 is realized by, for example, a double-sided tape structure, and by adhering one or more sheets, the vertical distance between the support 132 and the permanent magnet piece 133, and therefore the strength of the magnetic attractive force, can be adjusted. The magnetic attractive force between the support 132 and the permanent magnet piece 133 ensures contact between the downward connection terminal 115 and the upward connection terminal 150.
[0037] In the upper portion 203 of the case 202, a pair of guide members 135, 136 guide both side portions of the cell culture vessel 103 in the width direction X in the longitudinal direction Y. A central position 146 between the guide members 135, 136 and a central position 147 of the permanent magnet piece 133 are configured to coincide along the width direction X. Therefore, the magnetic attraction force is equal on the left and right of the central positions 146, 147 along the width direction X. Furthermore, these central positions 146, 147 are near the center of gravity along the width direction X of the cell culture vessel 103 placed on the observation device main body 104. Therefore, when an operator grasps both side portions of the cell culture vessel 103 with the fingers of one hand at positions indicated by the operation notches 137, 138 (FIGS. 1, 7, and 12) and moves the cell culture vessel 103 up and down, for example, there is no risk of the cell culture vessel 103 undesirably tilting to the left or right of the central positions 146, 147 along the width direction X. This prevents the cell culture vessel 103 from being subjected to an impact, and prevents the cells and culture medium from shaking and spilling out of the storage space 109.
[0038] The permanent magnet piece 133 may be a permanent magnet such as an alloy magnet, a ferrite magnet, a rare earth magnet, etc. The material of the magnet may be metal, a sintered body, a plastic magnet made by mixing a ferromagnetic material with plastic, or a rubber magnet made by mixing a ferromagnetic material with rubber.
[0039] A detection hole 177 is formed in the rear (left side in FIG. 11) of the case 202 of the observation device main body 104. One or more (e.g., two) control boards 116a, 116b (collectively indicated by reference numeral 116) are fixed inside the case 202 of the observation device main body 104 by mounting seats 225, 226 ( FIG. 9 ), 227 ( FIG. 11 ) extending downward from the upper part 203 of the case 202. A culture environment detection element 178 facing the external culture environment through the detection hole 177 is provided on the control board 116a. The culture environment detection element 178 may be configured to detect, for example, at least one of the temperature, humidity, carbon dioxide (CO2) concentration, and atmospheric pressure of the culture environment, and the acceleration of the observation device main body 104, and therefore the cell culture vessel 103. The detection output of the culture environment detecting element 178 is given to a memory circuit 121 and a processing circuit 142 in a signal processing circuit 201 shown in Fig. 18, which will be described later, and can be extracted by communicating with an external circuit via a connection terminal 220. By providing such a culture environment detecting element 178 in the observation device main body 104, if a problem occurs in the quality control of the cultured cells due to a malfunction of the cell culture device or the like, the cause can be identified based on the detection value of the culture environment detecting element 178, and the effect on the cells can be known.
[0040] Figure 12 is a cross-sectional view taken along the cutting line XII-XII in Figure 10. Operation notches 137 and 138 are formed in the upper part 203 of the case 202 of the observation device main body 104 near the protrusion 173 where the above-mentioned permanent magnet piece 133 is disposed. The positions where these operation notches 137 and 138 are formed are near the center of gravity along the longitudinal direction Y of the cell culture vessel 103 placed on the observation device main body 104.
[0041] The operation notches 137, 138 are formed, for example, slightly offset from the protrusion 173 and rearward toward the other end in the longitudinal direction Y (diagonally upper right in FIG. 7 , leftward in FIGS. 9 and 10 ), on both sides in the width direction X, recessed downward at substantially the same position in the longitudinal direction Y. As clearly shown in the above-mentioned FIG. 7 , one operation notch 137 has a semicircular shape with a base corresponding to the thumb of the operator's right hand, while the other operation notch 138 is elongated in the longitudinal direction Y corresponding to the aligned index finger and middle finger of the operator's right hand. The operation notches 137, 138 clearly indicate the locations on the outer walls 166 of the cell culture vessel 103 in the width direction X to be grasped with the fingers when the cell culture vessel 103 placed on the observation device main body 104 is displaced upward to be removed, and when the cell culture vessel 103 is displaced downward to be placed on the observation device main body 104. This allows the operator to pinch and grasp both sides of the cell culture vessel 103 with the fingers of one hand.
[0042] By selecting the positions where the operation notches 137, 138 are formed in this manner, even if the magnetic attractive force suddenly changes depending on the distance between the ferromagnetic support 132 of the cell culture vessel 103 and the permanent magnet piece 133 at the stopper 171 when the operator displaces the cell culture vessel 103 up and down or moves it sideways relative to the observation device main body 104, accurate observation can be performed without applying any shock to the cells and culture medium in the storage space 109, and it is also easy to keep the cell culture vessel 103 in a desired position, for example, a horizontal position. Therefore, shaking and overflow of the cells and culture medium from the storage space 109 is prevented.
[0043] The test plate with wells in the aforementioned Patent Document 1 is equipped with an edge card connector, and electrical connection is achieved by inserting its contacts into sockets through horizontal lateral displacement. Therefore, in Patent Document 1, there is a risk that cells and culture medium in the wells may spill out due to lateral impact during electrical attachment and detachment. In this embodiment, electrical connection is achieved by the operation of placing and detaching the cell culture vessel 103 up and down relative to the observation device main body 104, so no lateral impact is applied to the cell culture vessel 103, and the problem with the cell culture vessel 103 is solved. In other embodiments of the present disclosure, a connector that achieves electrical connection through lateral displacement may be used.
[0044] FIG. 13 is an enlarged cross-sectional view showing the upward connection terminal 150 of FIG. 10. The upward connection terminal 150, sometimes called a pogo pin, includes a terminal pin 151, a cylindrical body 152, and a terminal spring 153. The terminal pin 151 has a contact portion 155 that contacts the downward connection terminal 115, and a bulge portion 156 that is connected to the lower portion of the contact portion 155 and has a larger outer diameter than the contact portion 155. The cylindrical body 152 has an insertion portion 157 through which the contact portion 155 passes, a cylindrical portion 158 that is connected to the lower portion of the insertion portion 157 and through which the bulge portion 156 passes, and a base portion 159 that closes the lower portion of the cylindrical portion 158. The terminal spring 153 is interposed within the cylindrical portion 158 between the bulge portion 156 and the base portion 159 of the terminal pin 151 and applies an upward elastic force to the terminal pin 151. The outer peripheral surface of the terminal pin 151 and the inner peripheral surface of the cylindrical portion 158 of the cylindrical body 152 come into contact with each other, thereby establishing electrical continuity. In a natural, non-contact state, the top of the contact portion 155 is located above a plane including the mounting surface 108a. When the cell culture vessel 103 is placed on the observation device main body 104, the weight of the cell culture vessel 103 and the magnetic attraction force between the ferromagnetic support 132 of the cell culture vessel 103 and the permanent magnet piece 133 at the stop portion 171 cause the terminal spring 153 to reliably achieve resilient contact between the top of the contact portion 155 and the downward connection terminal 115.
[0045] The gasket 134 is disposed between the upper portion 203 of the case 202 of the observation device main body 104 and the outer peripheral surface of the cylindrical portion 158. This prevents liquid containing the culture medium from entering the case 202, and protects the control board 116 and other components inside the case 202.
[0046] 9 to 13, bases 159 of upward connection terminals 150 are erected on control board 116a and connected to analog front end 119 of signal processing circuit 201 via wiring 117 (FIG. 18). A secondary battery 224 such as a lithium battery is mounted on control board 116b. The lower part of case 202 is closed by bottom cover 228.
[0047] In other embodiments, the upward connection terminal 150 is not limited to the above-described configuration, and may have any configuration that achieves electrical connection by resilient contact with the downward connection terminal 115. In other embodiments, the contact between the upward connection terminal 150 and the downward connection terminal 115 does not have to be resilient.
[0048] FIG. 14 is a cross-sectional view of the connection body 181, showing the wiring board 182 unfolded, in a simplified form for ease of understanding. FIG. 15 is a plan view of the wiring board 182 of FIG. 14 with a portion thereof omitted, and FIG. 16 is a bottom view of the wiring board 182 of FIG. 14 with a portion thereof omitted. The wiring board 182 connects the detection element circuit 107 to the upward connection terminal 150 of the observation device main body 104 via the downward connection terminal 115 connected thereto. In the wiring board 182, the conductor 212 formed on the lower surface of the base film 211 in FIG. 14 is connected to the downward connection terminal 115 formed on the upper surface in FIG. 14 via a through-hole conductor 213 that penetrates the base film 211 in the thickness direction at the terminal portion 186. Insulating layers 214 and 215 formed on the base film 211 protect the conductor 212 and the downward connection terminal 115.
[0049] The conductor 212 forms terminal conductors 216 exposed from the insulating layer 214 near the other end in the longitudinal direction Y (left side in FIG. 14 ) in the connection portion 184 of the wiring board 182. The terminal conductors 216 are individually connected in the thickness direction to terminal conductors 217 of the detection element circuits 107 formed on the slide glass 191 via anisotropic conductive films 218. The insulating layer 219 of the detection element circuits 107 protects the terminal conductors 217 of the detection element circuits 107.
[0050] FIG. 17 is a simplified plan view showing the detection region 143 provided in each storage space 109 of the well member 101. The detection element circuit 107 formed on the glass slide 191 of the bottom substrate 110 has a detection region 143 for each storage space 109. A typical example of a detection element in an embodiment of the present disclosure is a photodiode 6. The light-receiving region of each photodiode 6 that receives reflected light, scattered light, or transmission holes from cells or the culture medium is called a pixel 3. In each detection region 143, the photodiodes 6, and therefore the pixels 3, are arranged in a matrix at a pitch P (e.g., six columns in the width direction X and six rows in the length direction Y, for a total of 36), as shown in FIG. 17. One or more pixels 3 can be combined to determine the presence or absence of light, the intensity of the received light, and obtain a two-dimensional image. The pitch P of the pixels 3 is not limited, but may be, for example, 300 μm, 150 μm, 120 μm, 100 μm, 90 μm, 60 μm, etc., and can be set according to the required specifications of the detection element.
[0051] 18 is a block diagram showing the electrical configuration of the detector circuit 107 on the bottom substrate 110 and the control substrate 116 built into the observation device main body 104. The detector circuit 107 on the bottom substrate 110 may be realized by an imaging element such as a CMOS (Complementary Metal-Oxide Semiconductor) image sensor, and includes a pixel circuit 111 that amplifies a light-receiving signal representing the amount of light received, generated by the photodiode 6 of the pixel 3, a sample-and-hold circuit 112 that further amplifies the signal amplified by the pixel circuit 111, a row-selection shift register 113, a column-selection shift register 114, and a downward connection terminal 115, and may further include an arithmetic processing circuit. With this configuration, to output a signal to the outside of the bottom substrate 110, the image signal transferred row by row is held in the sample-and-hold circuit 112, and is then read out by sequentially outputting the signal horizontally for each pixel by column selection. Because the signal is amplified by the sample-and-hold circuit 112, it is possible to reduce external noise that is introduced into the downward connection terminal 115 on the bottom substrate 110, the upward connection terminal 150 on the observation device main body 104, and the wiring 117 connected to the signal processing circuit 201 on the control substrate 116. The signal processing circuit 201 on the control substrate 116 includes a power supply circuit 118, an analog front end (AFE) 119 connected to the power supply circuit 118, a logic circuit (Field Programmable Gate Array; FPGA) 120, a memory circuit 121, and a processing circuit (Micro Controller Unit; MCU) 142 serving as a control unit. An output signal from the processing circuit 142 can be communicated with and extracted from an external circuit via a connection terminal 220. This communication can be performed, for example, via Bluetooth (registered trademark), infrared, near field communication (NFC), a wireless local area network (LAN), a wired LAN, a wide area network (WAN), the Internet, or any other communication medium, or any combination thereof. It is also possible to use USB (Universal Serial Bus) as an interface.In this way, the detection element circuit 107 and the control board 116 can exchange signals via the wiring 117. The observation device main body 104 is provided with a secondary battery 224 in association with the power supply circuit 118.
[0052] 1, a power button 105 is provided on one side of the case 202 of the observation device main body 104, in front of and closer to one end in the longitudinal direction Y than the operation notch 138. One or more (for example, three) indicator lights 221 are provided on the upper part 203 of the case 202, behind and closer to the other end in the longitudinal direction Y than the operation notch 137. The indicator lights 221 may indicate, for example, the operating state, such as power-on by the power button 105, charging of the secondary battery 224, and dimming control of the light source 102.
[0053] The detection element circuit 107 can be realized by an integrated circuit with a relatively simple circuit configuration, because the signal obtained therefrom is a detection value at each time. Therefore, when the cells and culture medium to be observed are replaced, the used well member 101 and / or bottom substrate 110 are discarded and disposed of, and even if a new cell culture vessel 103 is replaced, the disposal cost can be kept low. In contrast, the observation device main body 104 is equipped with a control board 116, includes a circuit configuration more complex than that of the detection element circuit 107, and includes integrated circuits such as a Si substrate, and is commonly used for multiple replaced cell culture vessels 103. Therefore, even if the used well member 101, bottom substrate 110, and cell culture vessel 103 are discarded, the observation device main body 104 continues to be used repeatedly, thereby successfully achieving cost reduction effects. In this way, the cell observation device 100 can be installed in the culture environment of a cell culture device, and desired data on the cultured cells can be obtained with high precision, enabling low-cost, highly reproducible cell observation. Examples of cell characteristics include obtaining the culture conditions such as the presence of cells, the state of cell growth, and the state of cell death in cell observation. Also, examples of culture medium characteristics include obtaining the culture environment conditions such as the temperature of the culture medium and the pH value of the culture medium. Therefore, by using the cell observation device 100, it is possible to monitor the state of cells being cultured in the cell culture device and the culture environment in real time, and to manage the quality of cells being cultured, which was difficult with conventional technology.
[0054] FIG. 19 is a plan view showing the configuration of a pixel 3, and FIG. 20 is a cross-sectional view taken along the section line XXa-XXb-XXc-XXd-XXe in FIG. 9. A plurality of pixels 3, each including a photodiode 6 as a detector element, are arranged in a matrix at a pitch P, as shown in FIG. 17, in a detector circuit 107 on a base substrate 110. The photodiode 6 includes a cathode electrode 63 and wirings 7, 8, 9, and 10. The cathode electrode 63 is made of metal and does not transmit light, so light passes through gaps between the cathode electrode 63 and the wirings 7, 8, 9, and 10 that conduct currents and control signals for driving each pixel 3. The detector circuit 107 includes a first insulating layer 5, a second insulating layer 20, a third insulating layer 23, a fourth insulating layer 21, and a fifth insulating layer 25. A second insulating layer 20 is laminated on the second surface 5b of the first insulating layer 5, and a third insulating layer 23 and a fourth insulating layer 21 are laminated on the first surface 20b of the second insulating layer 20. The first insulating layer 5, the second insulating layer 20, the third insulating layer 23, the fourth insulating layer 21, and the fifth insulating layer 25 may be made of an inorganic insulating layer such as silicon oxide (SiO2) or silicon nitride (Si3N4), or an organic insulating layer such as an acrylic resin or a polycarbonate resin. With this configuration, light from the specimen, which is the cells and culture medium in one well member 101, is received by multiple pixels 3, allowing the state and changes of the specimen to be reliably observed.
[0055] The detector circuit 107 includes a light-transmitting region covered with a transparent inorganic film or a transparent organic film. The light-receiving section 106 of the pixel 3 includes a plurality of photodiodes 6 serving as light-receiving elements. Each of the photodiodes 6 includes a cathode electrode 63 serving as a lower electrode, a semiconductor layer 61 serving as a photoelectric conversion layer located on the cathode electrode 63, and an anode electrode 62 serving as an upper electrode located on the semiconductor layer 61. The cathode electrode 63 and the anode electrode 62 are electrically connected to a plurality of wirings 7, 8, 9, and 10 arranged so as to overlap the cathode electrode 63 in a planar view. A light-transmitting region is located between each photodiode 6, and light from the light source 102 is irradiated onto the cell-containing medium through the light-transmitting region. The anode electrode 62 serving as an upper electrode may be formed of a transparent conductive film material to efficiently supply light reflected or scattered by the cell-containing medium to the semiconductor layer 61.
[0056] The multiple wirings 7 are power supply lines for supplying a power supply voltage VDD to the pixels 3. The power supply lines 7 are connected to an external power supply circuit 118 (FIG. 18). In addition, the power supply lines 7 are arranged for each pixel column of the pixels 3 and are connected to the pixels 3 in each column. The power supply lines 7 may be connected to the power supply circuit 118 via a drive circuit 4 described next.
[0057] The driving circuit 4 may be included in the light receiving unit 106. The driving circuit 4 may be configured to generate control signals to be supplied to each of the plurality of pixels 3 and to read out detection signals (voltage signals) from each of the plurality of pixels 3. The driving circuit 4 may include a sample-and-hold circuit 112, a row selection shift register 113, and a column selection shift register 114 shown in FIG. 18, and may be located on one main surface 52a of the substrate 52 (FIG. 20). The driving circuit 4 may include, for example, an integrated circuit (IC), a large-scale integration (LSI), or the like. The driving circuit 4 may be mounted on one main surface 52a of the substrate 52 by means of, for example, a chip-on-glass (COG) method, or may be mounted on the other main surface 52b opposite to the one main surface 52a. The driving circuit 4 may be a thin-film circuit formed on the one main surface 52a by a thin-film formation method such as a chemical vapor deposition (CVD) method.
[0058] The multiple wirings 8 are readout signal lines for reading out each voltage signal READ1(m) (where m is a natural number) generated in each pixel 3. The readout signal lines 8 are arranged for each pixel column of pixels 3 and are connected to the pixels 3 in each column. The readout signal lines 8 are connected to the drive circuit 4.
[0059] The multiple wirings 9 are reset signal lines for resetting voltage signals READ1(m) (here, m is a natural number, collectively referred to as "READ") of the pixels 3 in each row of the multiple pixels 3. The multiple reset signal lines 9 are arranged for each pixel row of the multiple pixels 3 and are connected to the pixels 3 in each row. The multiple reset signal lines 9 are connected to the drive circuit 4 and supply reset signals RST(n) (here, n is a natural number) generated by the drive circuit 4 to the pixels 3 in each row. The multiple wirings 10 are selection signal lines for setting (selecting) the readout period of each voltage signal READ generated in each of the multiple pixels 3.
[0060] The multiple power supply lines 7, the multiple readout signal lines 8, and the multiple reset signal lines 9 may be located between the detection element circuit 107 and the first insulating layer 5 that is laminated thereon, may be located inside the first insulating layer 5, or may be located on the first insulating layer 5. The power supply lines 7, the readout signal lines 8, the reset signal lines 9, and the selection signal lines 10 may be made of a metal such as gold (Au), tantalum (Ta), neodymium (Nd), tungsten (W), titanium (Ti), molybdenum (Mo), aluminum (Al), chromium (Cr), silver (Ag), or an alloy thereof.
[0061] Each of the plurality of pixels 3 includes a first insulating layer 5, a photodiode 6, an amplifier transistor 11, a reset transistor 12, and a selection transistor 13.
[0062] The first insulating layer 5 is located on one main surface 52a of the substrate 52. The first insulating layer 5 has a first surface 5a facing the substrate 52 and a second surface 5b opposite to the first surface 5a. The first insulating layer 5 may be made of an inorganic material such as silicon oxide (SiO2) or silicon nitride (Si3N4), or may be made of an organic material such as an acrylic resin or a polycarbonate resin.
[0063] The photodiode 6 is located on the second surface 5b of the first insulating layer 5. The photodiode 6 has a semiconductor layer 61, an anode electrode 62, and a cathode electrode 63. The semiconductor layer 61 is stacked on the cathode electrode 63 on the second surface 5b of the first insulating layer 5. The semiconductor layer 61 has a third surface 61a facing one major surface 63a of the cathode electrode 63, and a fourth surface 61b opposite the third surface 61a. The anode electrode 62 is located on the fourth surface 61b of the semiconductor layer 61, and the cathode electrode 63 is located on the third surface 61a of the semiconductor layer 61. The semiconductor layer 61 may be made of, for example, silicon (Si), germanium (Ge), gallium arsenide (GaAs), indium gallium arsenide (InGaAs), or the like. The anode electrode 62 may be a transparent conductive layer made of, for example, indium tin oxide (ITO), indium zinc oxide (IZO), etc. The cathode electrode 63 may be a non-transparent metal layer made of, for example, a metal such as Ta, Nd, W, Ti, Mo, Al, Cr, Ag, etc., or an alloy of these.
[0064] The photodiode 6 may be a PN-type photodiode or a PIN-type photodiode. In the light receiving unit 106 of this embodiment, the photodiode 6 is a PIN-type photodiode, and the semiconductor layer 61 has a structure in which an intrinsic semiconductor layer (I-type semiconductor layer) 61e is sandwiched between a P-type semiconductor layer 61c and an N-type semiconductor layer 61d. Compared to PN-type photodiodes, PIN-type photodiodes have the advantages of a faster response speed and a smaller dark current.
[0065] The amplifier transistor 11 and the reset transistor 12 are three-terminal elements having a gate electrode, an input electrode, and an output electrode. The amplifier transistor 11 and the reset transistor 12 may be configured as thin film transistors (TFTs). In the light receiving unit 106 of this embodiment, the amplifier transistor 11 and the reset transistor 12 are configured as n-channel TFTs. Hereinafter, the amplifier transistor 11 and the reset transistor 12 may be collectively referred to as TFTs 11 and 12.
[0066] The amplifier transistor 11 has a gate electrode connected to a cathode electrode 63, an input electrode (drain electrode) connected to one of a plurality of power supply lines 7, and an output electrode (source electrode) connected to one of a plurality of read signal lines 8.
[0067] The reset transistor 12 has a gate electrode connected to one of the multiple reset signal lines 9, an input electrode (drain electrode) connected to the power supply line 7, and an output electrode (source electrode) connected to the cathode electrode 63 and the gate electrode of the amplifier transistor 11.
[0068] As shown in FIG. 20 , the TFTs 11 and 12 may include a gate electrode 15, a gate insulating layer 16, a semiconductor layer 17, a source electrode 18, and a drain electrode 19. The gate electrode 15 is located on one major surface 52a of a substrate 52. The gate insulating layer 16 is made of, for example, SiO 2 or the like, and covers the one major surface 52a of the substrate 52 and the gate electrode 15. The semiconductor layer 17 is located on the gate insulating layer 16 and covers the gate electrode 15. The semiconductor layer 17 is made of, for example, low-temperature polysilicon (LTPS) or the like. The semiconductor layer 17 has a channel region (also referred to as a channel portion) 17a located directly above the gate electrode 15, a source region 17b located at one end of the channel portion 17a, and a drain region 17c located at the other end opposite the one end of the channel portion 17a. The source region 17b and the drain region 17c are made of, for example, n+-type LTPS or the like. The semiconductor layer 17 may have a lightly doped drain (LDD) region 17d between the channel portion 17a and the source region 17b and between the channel portion 17a and the drain region 17c. The source electrode 18 and the drain electrode 19 are made of a metal such as tantalum (Ta), neodymium (Nd), tungsten (W), titanium (Ti), molybdenum (Mo), aluminum (Al), chromium (Cr), or silver (Ag), or an alloy thereof. The source electrode 18 and the drain electrode 19 are connected to the source region 17b and the drain region 17c, respectively. The source electrode 18 and the drain electrode 19 are connected to the power supply line 7, the readout signal line 8, the reset signal line 9, or connection wiring formed in the pixel 3. The source electrode 18 and the drain electrode 19 may be formed integrally with the wiring.
[0069] 20, the pixel 3 has a passivation film 24 that covers the TFTs 11 and 12 and the gate insulating layer 16, and an insulating film (fifth insulating layer) 25 that covers the passivation film 24. The passivation film 24 may be made of, for example, silicon oxide (SiO2), silicon nitride (Si3N4), or the like. The insulating film 25 may be made of, for example, acrylic resin, polycarbonate resin, or the like.
[0070] The semiconductor layer 17 is not limited to LTPS, and may be made of, for example, amorphous silicon (a-Si), indium gallium zinc oxide, etc. In addition, although the example in Fig. 7 shows a case where the TFTs 11 and 12 are bottom gate type (inverted staggered type), the TFTs 11 and 12 may also be top gate type (staggered type).
[0071] The pixel 3 generates a light-receiving voltage VPD corresponding to the charge accumulated in the photodiode 6 at the gate electrode of the amplifier transistor 11. The amplifier transistor 11 is a source follower transistor that amplifies the light-receiving voltage VPD and outputs the amplified light-receiving voltage VPD as a voltage signal READ to the readout signal line 8. The gate electrode of the amplifier transistor 11 is connected to the output electrode of the reset transistor 12. As a result, after the amplifier transistor 11 outputs one frame's worth of voltage signal READ, the reset signal RST(n) can be set to a high (H) signal to turn the reset transistor 12 into a conductive (ON) state, thereby resetting the light-receiving voltage VPD and the voltage signal READ.
[0072] 17, 19, and 20, the pixel 3 further includes a first contact hole 14 and a second contact hole 22. The first contact hole 14 penetrates the first insulating layer 5 in the thickness direction from the second surface 5b to the first surface 5a, and electrically connects the cathode electrode 63 to the gate electrode of the amplifier transistor 11 and the output electrode (source electrode) of the reset transistor 12. As shown in FIG. 20, for example, the first contact hole 14 is located between the amplifier transistor 11 and the reset transistor 12 in the extension direction of the power supply line 7 (the vertical direction in FIG. 19).
[0073] In the light receiving section 106, the elements (photodiode 6, amplifier transistor 11, reset transistor 12, etc.) and wiring (power supply line 7a, read signal line 8a, reset signal line 9a, etc.) that constitute the pixel 3 can be efficiently arranged. As a result, the pixel pitch P of the multiple pixels 3 can be reduced.
[0074] The first contact hole 14 and the second contact hole 22 are formed so as not to overlap each other in a plan view. The photodiode 6 is fabricated by sequentially stacking a metal layer serving as the cathode electrode 63, a semiconductor layer 61, and a transparent conductive layer serving as the anode electrode 62 on the first contact hole 14. Therefore, a recess corresponding to the shape of the first contact hole 14 is inevitably present on the upper surface 62a of the photodiode 6 (the surface facing the second insulating layer 20). Therefore, when the first contact hole 14 and the second contact hole 22 are formed by etching, the resist used in the etching may remain in the recess, which may reduce the reliability of the electrical connection between the anode electrode 62 and the conductive layer 22a. Forming the first contact hole 14 and the second contact hole 22 so as not to overlap each other allows for a good connection between the anode electrode 62 and the conductive layer 22a, thereby improving the reliability of the photodetection circuit 30 (see FIGS. 25A to 25D, described below) associated with the photodiode 6.
[0075] As shown in FIG. 20 , the first contact hole 14 may include a conductive layer 14a disposed on the inner circumferential surface of a recess 5c formed in a predetermined portion of the first insulating layer 5, and a filler 14b filled in the recess 5c (i.e., the space surrounded by the conductive layer 14a). The first contact hole 14 is a so-called penetrating conductor and is provided in the recess 5c as a through-hole. The recess 5c may be formed by an etching method such as dry etching. The dry etching method used to form the recess 5c may be reactive ion etching. The conductive layer 14a may be composed of a metal such as Ta, Nd, W, Ti, Mo, Al, Cr, or Ag, or an alloy thereof. The conductive layer 14a may be formed by extending a portion of the cathode electrode 63 of the photodiode 6 into the recess 5c, as shown in FIG. 20 . Filler 14b filled in recess 5c may be made of an organic material such as acrylic resin, silicone resin, polyimide, polyimideamide, benzocyclobutene, polysiloxane, or polysilazane, or may be made of a photosensitive organic resin, a thermosetting resin, etc. Filler 14b may be formed by, for example, as shown in FIG. 20 , having a part of N-type semiconductor layer 61d and a part of intrinsic semiconductor layer 61e embedded in recess 5c.
[0076] The light receiving unit 106 may further include a plurality of selection signal lines 10. The plurality of selection signal lines 10 are wirings for setting (selecting) the readout period of each voltage signal READ generated in each of the plurality of pixels 3. The plurality of selection signal lines 10 are arranged for each pixel row of the plurality of pixels 3 and are connected to the pixels 3 in each row. The plurality of selection signal lines 10 are connected to the drive circuit 4 and supply the selection signal RS(n) generated by the drive circuit 4 to the pixels 3 in each row.
[0077] Each of the multiple pixels 3 may have a selection transistor 13. The selection transistor 13 may be a three-terminal element having a gate electrode, an input electrode, and an output electrode. The selection transistor 13 may be configured as an n-channel TFT, similar to the amplifier transistor 11 and the reset transistor 12. Hereinafter, the amplifier transistor 11, the reset transistor 12, and the selection transistor 13 may be collectively referred to as TFTs 11, 12, and 13.
[0078] The selection transistor 13 may have a gate electrode connected to one of a plurality of selection signal lines 10, an input electrode (drain electrode) connected to the output electrode of the amplifier transistor 11, and an output electrode (source electrode) connected to a readout signal line 8. The output electrode of the amplifier transistor 11 may not be directly connected to the readout signal line 8 but may be connected to the readout signal line 8 via the selection transistor 13. The pixel 3 can output a voltage signal READ to the readout signal line 8 while the selection signal RS(n) is a high (H) signal and the selection transistor 13 is in a conductive (ON) state. This makes it possible to read out each voltage signal READ1(m) generated in the pixels 3 of each row of the plurality of pixels 3.
[0079] FIG. 21 is a partial plan view showing the state of observation of a specimen by light transmitted through the bottom substrate 110. With the bottom substrate 110, cells and foreign matter such as dirt, indicated by reference symbol G, can be confirmed by light transmitted through the bottom substrate 110 in the region where only transparent inorganic and organic films are formed. From such observation results, it can be determined whether the cell culture vessel 103 should be replaced. Therefore, if it is determined that replacement is necessary, the inexpensive cell culture vessel 103 can be separated from the expensive observation device main body 104 and replaced with a new cell culture vessel 103. From the viewpoint of ease of observation of foreign matter such as dirt, it is preferable that the pixel pitch P is large, and the transparent spacing between the pixel 3 and the adjacent pixel 3 is small. Δ 1. Δ 2 may be larger than the width of pixel 3. In other words, in order to enlarge the light-transmitting region, the width of the light-receiving element through which light does not pass is made smaller, and the width of the light-transmitting region through which light passes is made smaller. Δ 1.Δ 2 may be made larger than the width of the light receiving element.
[0080] FIG. 22A is a plan view showing a cell culture vessel 103 having an auxiliary observation region outside the pixel region that is composed only of an inorganic film and an organic film, or an inorganic film. FIG. 22B is a plan view showing another example of a cell culture vessel 103 having an auxiliary observation region outside the pixel region that is composed only of an inorganic film and an organic film, or an inorganic film. The cell culture vessel 103 shown in FIG. 22A has a pixel region 1135A including six storage spaces 109 in a plan view. The area outside this pixel region 1135A is designated as auxiliary observation region 1135B, which is indicated by diagonal lines and is composed only of an inorganic film and an organic film or an inorganic film. The cell culture vessel 103 shown in FIG. 22B has a pixel region 1135C including six pixels 3 and half of the remaining two storage spaces 109 in a plan view. The area outside this pixel region 1135C is designated as auxiliary observation region 1135D, which is indicated by diagonal lines and is composed only of an inorganic film and an organic film or an inorganic film. Therefore, while organic films have a light or yellowish color, inorganic films are colorless and are therefore not affected by coloring like organic films. Unlike pixels 3, auxiliary observation regions 1135B and 1135D do not have lower electrodes or wiring formed therein, and therefore can efficiently guide light irradiated from below bottom substrate 110 to above the culture medium, allowing for microscopic observation other than observation using photodiode 6. The observation results of auxiliary observation regions 1135B and 1135D can also be used to verify the observation results using photodiode 6.
[0081] 23 is a circuit diagram showing the configuration of the sample and hold circuit 112, and FIG. 24 is a timing chart for explaining the operation of the sample and hold circuit 112. The sample and hold circuit 112 includes a first transistor 122, a second transistor 123, a first capacitor 124, a second capacitor 125, a third transistor 126, an amplifier 127, and a fourth transistor 128.
[0082] The sample-and-hold circuit 112 outputs a differential signal between the exposure data and the reset data. During period A between times t1 and t2, the exposure readout signal from pixel 3 is transferred to the node at point α by turning on the second transistor 123. At the same time, the node at point β is reset to VGH by turning on the third transistor 126. During period B between times t2 and t3, the reset readout signal from pixel 3 is transferred to the node at point α. At this time, the node at point β is floating by turning off the third transistor 126, so a differential signal between the reset readout signal and the exposure readout signal is written by coupling with the first capacitor 124. During period C after time t3, a voltage corresponding to the differential voltage is output for each sequentially selected column.
[0083] Fig. 25A is a diagram illustrating the photodetection circuit 30 in a reset state, Fig. 25B is a diagram illustrating the photodetection circuit 30 in an exposure state, Fig. 25C is a diagram illustrating the photodetection circuit 30 in an exposure readout state, and Fig. 25D is a diagram illustrating the photodetection circuit 30 in a reset readout state. Fig. 26 is a timing chart for explaining the operation of the pixel circuit 111. The light-sensing circuit of this embodiment includes a photodetection circuit 30, a differential circuit, and a control circuit.
[0084] As shown in FIGS. 25A to 25D, the photodetection circuit 30 includes a photodiode 6, an amplifier transistor 11, a reset transistor 12, and a selection transistor 13.
[0085] The photodiode 6 has an anode electrode 62 and a cathode electrode 63. A bias voltage generated by the control board 116 may be applied to the anode electrode 62.
[0086] The amplifier transistor 11, the reset transistor 12, and the selection transistor 13 are three-terminal elements having a gate electrode, a source electrode, and a drain electrode. The amplifier transistor 11, the reset transistor 12, and the selection transistor 13 may be configured as thin film transistors (TFTs). The amplifier transistor 11, the reset transistor 12, and the selection transistor 13 may be configured as n-channel TFTs.
[0087] The amplifier transistor 11 has a gate electrode connected to the cathode electrode 63, a source electrode connected to the drain electrode of the selection transistor 13, and a drain electrode connected to the power supply line 7. The reset transistor 12 has a gate electrode connected to a reset signal line 9, a source electrode connected to the cathode electrode 63, and a drain electrode connected to the power supply line 7. The selection transistor 13 has a gate electrode connected to a selection signal line 10, a source electrode connected to a readout signal line 8, and a drain electrode connected to the source electrode of the amplifier transistor 11.
[0088] The photodetection circuit 30 has a reset state shown in Fig. 25A, an exposure state shown in Fig. 25B, an exposure readout state shown in Fig. 25C, and a reset readout state shown in Fig. 25D. The control circuit controls the states of the photodetection circuit 30 by controlling each of the reset signal RST(n) and the selection signal RS(n).
[0089] As shown in FIG. 25A, the reset state is a state in which the reset signal RST(n) is a high (High: H) signal and the selection signal RS(n) is a low (Low: L) signal. The H signal may be a signal with the same voltage as the first voltage VDD. The L signal may be a signal with the same voltage as the second voltage VSS. In the reset state, the reset transistor 12 is in a conductive state and the selection transistor 13 is in a non-conductive state. In the reset state, the voltage of the gate electrode of the amplifier transistor 11 (also called the gate voltage) is VDD-V TH1 Here, V TH1 refers to the threshold voltage of the reset transistor 12.
[0090] As shown in FIG. 25B, the exposure state is a state in which both the reset signal RST(n) and the selection signal RS(n) are set to L signals. In the exposure state, the reset transistor 12 and the selection transistor 13 are in a non-conductive state. In the exposure state, a current corresponding to the amount of light received by the photodiode 6 is output from the cathode electrode 63. Therefore, the gate voltage of the amplifier transistor 11 fluctuates according to the amount of light received by the photodiode 6, and is equal to or lower than VDD-V TH1 -V PHOTO Here, V PHOTO indicates the fluctuation of the gate voltage of the amplifier transistor 11 due to the current output from the cathode electrode 63. PHOTO is also called the exposure voltage.
[0091] As shown in FIG. 25C, the exposure read state is a state in which the reset signal RST(n) is an L signal and the selection signal RS(n) is an H signal. In the exposure read state, the reset transistor 12 is in a non-conductive state and the selection transistor 13 is in a conductive state. In the exposure read state, the gate voltage of the amplifier transistor 11 is a voltage (i.e., VDD-V TH1 -V PHOTO ), and the selection transistor 13 outputs a voltage corresponding to the gate voltage of the amplifier transistor 11 to the read signal line 8. The voltage in the exposure read state (hereinafter referred to as the exposure read voltage V EXP (also called VDD-V TH1 -V PHOTO -V TH2 where V TH2 indicates the threshold voltage of the amplifier transistor 11.
[0092] As shown in FIG. 25D, the reset read state is a state in which both the reset signal RST(n) and the selection signal RS(n) are H signals. In the reset read state, the reset transistor 12 and the selection transistor 13 are in a conductive state. In the reset read state, the gate voltage of the amplifier transistor 11 is a constant predetermined voltage VDD-V that is independent of the amount of light received by the photodiode 6.TH1 The selection transistor 13 outputs a voltage corresponding to the gate voltage of the amplifier transistor 11 to the read signal line 8. The voltage in the reset read state (hereinafter referred to as the reset read voltage V RST (also called VDD-V TH1 -V TH2 is given by
[0093] In other embodiments of the present disclosure, instead of the electrical connection by mechanical contact between the downward connection terminal 115 and the upward connection terminal 150 described above, an electrical connection may be achieved without mechanical contact by wireless communication, electromagnetic induction, or the like, to transmit and receive electrical signals between the detection element circuit 107 and the observation device main body 104, and to supply power from the observation device main body 104 to the detection element circuit 107. Even in such an embodiment without mechanical contact, the cell culture vessel 103 can be placed on the observation device main body 104 so that it can be detached vertically, thereby avoiding lateral impact on the cell culture vessel 103 and thereby preventing the cells and culture medium from spilling out from the storage space 109 of the well member 101.
[0094] In another embodiment, the light source 102 may be arranged above the well member 101 instead of below the well member 101 and may be configured to irradiate light into the accommodation space 109 .
[0095] The present disclosure can be implemented with the following configurations (1) to (26).
[0096] (1) An observation device main body 104 on which a cell culture vessel 103 is placed, a placement receiving portion 108 on which the cell culture vessel 103 is removably placed; a positioning portion 171 for regulating the position of the cell culture vessel 103 on at least one side of the placement receiving portion 108; a connection terminal 150 of the observation device main body 104 for receiving an output signal from the cell culture vessel 103; An observation device main body, wherein the positioning portion 171 is located between the connection terminal 150 of the observation device main body 104 and the receiving portion 108 in a plan view.
[0097] (2) The observation device main body according to (1) above, wherein the positioning portion 171 is a protrusion 173 that protrudes upward from the receiving portion 108.
[0098] (3) The observation device body according to (2) above, wherein a magnet 133 is disposed below the protrusion 173, and fixes the cell culture vessel 103 by magnetic attraction.
[0099] (4) The observation device body according to (1) above, wherein the connection terminal 150 of the observation device body 104 is an upward-facing connection terminal that resiliently contacts and connects with the connection terminal 115 provided on the cell culture vessel 103.
[0100] (5) A cell culture vessel 103 to be placed on the observation device main body 104, a base substrate 110 containing sensing elements 6 for detecting characteristics of cells and culture media; a connection terminal 115 of the cell culture vessel 103 for outputting an output signal from the detection element 6 to the outside; a support 132 for mounting the bottom substrate 110 on its upper side; The cell culture vessel has a support 132 fixed to the observation device main body 104 by magnetic attraction.
[0101] (6) The support body 132 includes a mounting portion 162 on which the bottom substrate 110 is mounted and a connection support portion 163; The cell culture vessel according to (5) above, wherein the connection support part (163) is made of at least a magnetic material, and the magnetic attraction force is fixed at the connection support part (163).
[0102] (7) A cell culture vessel described in (6) above, in which a wiring board 182 having a connection terminal 115 of the cell culture vessel 103 is arranged on the connection support portion 163, and the connection terminal 115 of the cell culture vessel 103 is located on the lower side of the support 132.
[0103] (8) The cell culture vessel according to (7) above, wherein the wiring board 182 is arranged from the upper side to the lower side of the support 132 so as to cover the edge of the support 132.
[0104] (9) A cell observation device 100 in which the observation device main body 104 described in (1) is equipped with the cell culture vessel 103 described in (5), The connection terminal 150 of the observation device main body 104 is connected to the connection terminal 115 of the cell culture vessel 103, The cell observation device in which the support 132 is fixed to the observation device main body 104 by magnetic attraction.
[0105] (10) The positioning portion 171 is a protrusion 173 that protrudes upward from the receiving portion 108, the protrusion 173 is located between the connection terminal 150 of the observation device main body 104 and the receiving portion 108 in a plan view, The support 132 includes a mounting portion 162 for mounting the bottom substrate 110 and a connection support portion 163, The cell observation device according to (9) above, wherein the connection support part 163 is made of at least a magnetic material, and the magnetic attraction force is fixed between the protrusion 173 and the connection support part 163.
[0106] (11) The connection terminal 150 of the observation device main body 104 is an upward connection terminal 150 facing the cell culture device, The connection terminal 115 of the cell culture vessel 103 is a downward connection terminal 115 facing the observation device main body 104, The cell observation device according to (9) above, wherein the upward connection terminal 150 and the downward connection terminal 115 are in elastic contact and electrically connected.
[0107] (12) A cell observation device as described in (11) above, in which a wiring board 182 equipped with the downward connection terminal 115 is arranged on the connection support part 163, and the downward connection terminal 115 is positioned on the lower side of the support 132.
[0108] (13) The upward connection terminal 150 is disposed at the position of the recess 172 adjacent to the protrusion 173, A cell culture device as described in (12) above, in which a retaining piece 183 is interposed between the downward terminal 115 and the support 132 to form a connection terminal portion 186 of the cell culture vessel 103, and the connection terminal portion 186 of the cell culture vessel 103 is fitted into the recess 172.
[0109] (14) The cell observation device according to (12) above, wherein the wiring board 182 is arranged from the upper side to the lower side of the support 132 so as to cover the edge of the support 132.
[0110] (15) (a) A cell culture vessel 103, (a1) a well member 101 forming one or more storage spaces 109 for storing and culturing cells and culture media; (a2) a bottom substrate 110 provided at the bottom of the well member 101, having a detection element circuit 107 including a detection element 6 for detecting characteristics of a cell or a culture medium contained in the containing space 109, and deriving an output signal related to the detection of the detection element 6; A cell culture vessel 103 having (b) An observation device main body 104, (b1) a placement receiving portion 108 on which the cell culture vessel 103 is removably placed; (b2) a signal processing circuit 201 that receives and processes an output signal related to the detection of the detection element 6 in the cell culture vessel 103 placed on the placement receiving portion 108; and an observation device main body 104 having A cell observation device comprising:
[0111] (16) The bottom substrate 110 has a connector 181 provided with a downward-facing connection terminal 115 that is connected to the detection element circuit 107, The placement receiving portion 108 is provided facing upward, The observation device main body 104 has an upward connection terminal 150 facing upward and connected to a signal processing circuit 201, The upward connection terminal 150 faces the downward connection terminal 115 of the cell culture vessel 103 placed on the receiving portion 108, and in this placed state, the downward connection terminal 115 and the upward connection terminal 150 come into elastic contact and are electrically connected, in the cell observation device described in (15).
[0112] (17) The cell observation device described in (16) above, wherein a magnetic force generator 161 is provided in the cell culture vessel 103 and the observation device main body 104, which generates a magnetic attraction force in a direction in which the downward connection terminal 115 and the upward connection terminal 150 approach each other.
[0113] (18) The lower surface of the bottom substrate 110 of the cell culture vessel 103 and the lower surface including the downward connection terminal 115 are in a virtual plane, The upper surface of the mounting receiving portion 108 is a mounting surface 108a on which the lower surface of the bottom substrate 110 is placed. The cell observation device described in (17) above, wherein the contact portion 155 of the upward connection terminal 150 that comes into contact with the downward connection terminal 115 is located above a plane including the placement surface 108a in a natural state when not in contact with the downward connection terminal 115, and achieves the resilient contact with the downward connection terminal 115 in the placement state.
[0114] (19) (c) The overall shape of the cell culture vessel 103 is rectangular in plan view; (d) the bottom substrate 110 is (d1) a slide glass 191 provided with the detection element circuit 107, forming the bottom of the accommodation space 109 of the well member 101, and removable from the well member 101; (d2) a support 132 having a mounting portion 162 that supports the slide glass 191, and a connection support portion 163 that is connected to the mounting portion 162, extends closer to one end of the longitudinal direction Y along the long side of the rectangle than the slide glass 191, and on which the connector 181 is arranged; (d3) a holder 129 that holds the mounting portion 162 of the support body 132 with the connection support portion 163 protruding toward the one end in the longitudinal direction Y and forms the lower surface of the bottom substrate 110; (e) the observation device main body 104 has a guide part 136 that guides the cell culture vessel 103 in the longitudinal direction Y; (f) A cell observation device as described in (18), wherein the bottom substrate 110 and the observation device main body 104 are provided with a stop portion 171 that prevents displacement of the cell culture container 103 in the longitudinal direction Y at a contact position where the downward connection terminal 115 and the upward connection terminal 150 come into contact.
[0115] (20) The stop portion 171 is The observation device comprises a protrusion 173 formed on the upper portion 203 of the observation device body 104 and a recess 172 adjacent to the protrusion 173, The support 132 is configured to be removably fitted, The cell observation device according to (19) above, wherein the magnetic force generator 161 is constituted by a permanent magnet piece 133 provided on the protrusion 173 and is magnetically attracted to the support 132 made of a ferromagnetic material.
[0116] (21) The upward connection terminals 150 are arranged in plurality at intervals in the width direction X perpendicular to the longitudinal direction Y in the observation device main body 104, The downward connection terminals 115 are arranged in plurality to correspond to and individually contact the upward connection terminals 150, The cell observation device according to (20) above, wherein the permanent magnet pieces 133 are arranged so that the distribution of the magnetic attractive force in the width direction X is uniform.
[0117] (22) The cell observation device described in (217) above, wherein the upper portion 203 of the observation device main body 104 is formed with downwardly recessed operation notches 137, 138 on both sides in the width direction X at a position near the protrusion 173 in the longitudinal direction Y, allowing an operator to grasp the cell culture vessel 103 with their fingers.
[0118] (23) (g) The upward connection terminal 150 is (g1) a terminal pin 151 having a bulging portion 156 connected to a lower portion of the contact portion 155 and having an outer diameter larger than that of the contact portion 155; (g2) a cylindrical body 152 having an insertion portion 157 through which the contact portion 155 is inserted, a cylindrical portion 158 connected to a lower portion of the insertion portion 157 and through which the bulging portion 156 is inserted, and a base portion 159 closing the lower portion of the cylindrical portion 158; (g3) a terminal spring 153 that is interposed between the terminal pin 151 and the base 159 in the cylindrical portion 158 and applies an upward elastic force to the terminal pin 151; (h) The cell observation device according to (20) above, wherein a gasket 134 is disposed between the upper portion 203 of the observation device main body 104 and the outer circumferential surface of the cylindrical portion 158.
[0119] (24) A light source 102 is provided below the mounting receiving portion 108 within the observation device body 104, The holder 129 and the support 132 are formed with openings 164 and 168, respectively, for guiding light from the light source 102 into the accommodation space 109 of the well member 101. The cell observation device described in (19) above, wherein the detection element 6 receives light from the light source 102 that is reflected, scattered, or transmitted by the cells or the culture medium, and derives a detection signal corresponding to the amount of light received to measure the characteristics of the cells or the pH of the culture medium.
[0120] (25) The cell observation device according to (15), wherein the detection element 6 detects the temperature of the cell or the culture medium based on an electrical characteristic that changes depending on temperature.
[0121] (26) The cell observation device described in (15) above, wherein the observation device main body 104 has a culture environment detection element 178 for detecting at least one of the external temperature, humidity, carbon dioxide (CO2) concentration and atmospheric pressure, and the acceleration of the cell culture container 103.
[0122] Although the embodiments of the present disclosure have been described in detail above, the present disclosure is not limited to the above-described embodiments, and various modifications and improvements are possible within the scope of the gist of the present disclosure. It goes without saying that all or part of the components constituting each of the above-described embodiments can be combined as appropriate within the scope of not contradicting each other. [Explanation of symbols]
[0123] 6 Detector element 100 Cell observation device 101 Well component 102 Light source 103 Cell culture vessels 104 Observation device body 107 Detector element circuit 108 Placement receiving part 108a Placement surface 109 Containment Space 110 Bottom board 115 Downward connection terminal 129 Holder 132 Support 133 Permanent magnet piece 134 Gasket 136 Information Department 137, 138 Operation notch 150 upward connection terminal 151 terminal pin 152 Cylinder 153 Terminal spring 155 Contact part 156 Bulge 157 Insertion part 158 Cylinder part 159 Base 161 Magnetic generator 162 Mounting section 164, 168 Openings 171 Stop part 172 recess 173 protrusion 178 Culture environment detection element 181 Connectors 186 Connection terminal 191 Glass slide 201 Signal Processing Circuit 203 Upper
Claims
1. An observation device main body on which a cell culture vessel is placed, a placement receiving portion on which the cell culture vessel is removably placed; a positioning portion for regulating the position of the cell culture vessel on at least one side of the placement receiving portion; a connection terminal of an observation device body that receives an output signal from the cell culture vessel; The observation device main body, wherein the positioning portion is located between the connection terminal of the observation device main body and the receiving portion in a plan view.
2. 2. The observation device body according to claim 1, wherein the positioning portion is a protrusion that protrudes upward from the receiving portion.
3. 3. The observation device body according to claim 2, wherein a magnet is disposed below the protrusion, and the cell culture vessel is fixed by magnetic attraction.
4. 2. The observation device body according to claim 1, wherein the connection terminals of the observation device body are upward-facing connection terminals that are brought into elastic contact for connection.
5. A cell culture vessel to be placed on an observation device body, a base substrate including sensing elements for detecting characteristics of cells and medium; a connection terminal of the cell culture vessel for outputting an output signal from the detection element to the outside; a support for mounting the bottom substrate on an upper side thereof; The support is fixed to the observation device body by magnetic attraction.
6. the support body includes a mounting portion on which the bottom substrate is mounted and a connection support portion, 6. The cell culture vessel according to claim 5, wherein the connection support part is made of at least a magnetic material, and the connection support part is fixed by a magnetic attraction force.
7. The cell culture vessel according to claim 6, wherein a wiring board having connection terminals for the cell culture vessel is disposed on the connection support part, and the connection terminals for the cell culture vessel are located below the support.
8. The cell culture vessel according to claim 7 , wherein the wiring substrate is arranged from the upper side to the lower side of the support so as to cover the edge of the support.
9. A cell observation device comprising the observation device body according to claim 1 and the cell culture vessel according to claim 5, a connection terminal of the observation device body and a connection terminal of the cell culture vessel are connected to each other; The cell observation device in which the support is fixed to the observation device body by magnetic attraction.
10. the positioning portion is a protrusion that protrudes upward from the receiving portion, the protrusion is located between the connection terminal of the observation device main body and the receiving portion in a plan view, the support body includes a mounting portion on which the bottom substrate is mounted and a connection support portion, 10. The cell observation device according to claim 9, wherein the connection support part is made of at least a magnetic material, and the protrusion and the connection support part are fixed by a magnetic attraction force.
11. the connection terminal of the observation device body is an upward connection terminal facing the cell culture device, The connection terminal of the cell culture device is a downward connection terminal facing the observation device main body, The cell observation device according to claim 9 , wherein the upward connection terminal and the downward connection terminal are in elastic contact and electrically connected.
12. The cell observation device according to claim 11, wherein a wiring board having the downward-facing connection terminals is disposed on the connection support part, and the downward-facing connection terminals are located below the support.
13. the upward connection terminal is disposed in a recess adjacent to the protrusion, The cell culture device according to claim 13, wherein a retaining piece is interposed between the downward terminal and the support to form a connection terminal portion of the cell culture vessel, and the connection terminal portion of the cell culture vessel is fitted into the recess.
14. The cell observation device according to claim 12, wherein the wiring board is arranged from the upper side to the lower side of the support so as to cover the edge of the support.
Citation Information
Patent Citations
Multi-detection bioelectronic test plate
JP6803164B2