Sensor Module

Abstract

To collectively evaluate susceptibilities to drugs by considering the concentrations of the solution of each drug.SOLUTION: A sensor module (1) has a plurality of sensor ICs (103A-103F) arranged on a substrate (100), and a plurality of micro wells (102A, 102B) formed so as to cover the surface edge of each sensor IC (103A-103F) for storing a specimen (106A, 106B) to be measured by each sensor IC (103A-103F).SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention relates to a sensor module for evaluating drug susceptibility to a drug that inhibits the growth of microorganisms. [Background technology]

[0002] Microorganisms such as bacteria have various benefits in food and medicine. When bacteria are pathogens, drugs can be used for treatment by suppressing bacterial growth with the addition of effective drugs.

[0003] Drug susceptibility (resistance) tests are performed to evaluate drugs that are effective in inhibiting bacterial growth. Drug susceptibility tests generally involve placing a culture medium containing bacteria in a dish, and measuring the zone of inhibition of bacterial culture growth that appears around the solid drug. This allows the antibacterial activity of drugs to be evaluated, as an inhibition zone can be observed around effective drugs, indicating that no bacterial growth occurs.

[0004] In addition to this inhibition zone determination method, broth microdilution is sometimes used as a drug susceptibility test method for efficiently evaluating the presence or absence of drug susceptibility and the optimal drug concentration. This broth microdilution is a testing system that evaluates drug susceptibility based on the change in turbidity caused by bacterial growth in a multi-well having multiple wells, and can evaluate drug susceptibility for each drug, taking into account the drug solution concentration, for example.

[0005] The microdilution method has the problem that it takes time for bacteria to grow because the evaluation criteria are the turbidity observation in the multi-well, and the result of the proliferation of microorganisms is confirmed. In addition, there are problems such as the need for a high-resolution microscope and image discrimination, and the lack of quantitativeness because real-time observation is not possible. Furthermore, the number of wells that can be used in the multi-well used in the microdilution method is fixed, such as 96 wells or 384 wells, and when the number of tests or the number of chemical solutions are flexibly changed, there may be unnecessary empty holes.

[0006] Instead of the broth microdilution method that evaluates turbidity, there is also a drug susceptibility test method that evaluates the fluorescence that appears when a fluorescent reagent is inserted and the composition of proteins, etc. changes. However, this method of evaluating fluorescence has the problem that it requires a microscope with high resolution and fluorescence sensitivity, and image discrimination, to confirm the change in the evaluation target.

[0007] In any case, in order to perform drug susceptibility testing using the above-mentioned broth microdilution method or other methods, it is necessary to confirm changes in protein composition by bacterial growth, which poses the problem that real-time observation is difficult.

[0008] In recent years, biosensors using integrated circuit (IC) technology have been actively developed. For example, Patent Document 1 discloses a sensor IC that measures changes in the complex dielectric constant of a liquid as an evaluation target by placing the liquid on the surface of the IC. This sensor IC is provided with an LC oscillator that performs an oscillation operation within the range of 30 GHz to 200 GHz. The sensor IC senses changes in the dielectric constant of the evaluation target liquid from changes in the oscillation frequency of the LC oscillator.

[0009] Furthermore, the sensor IC described in Patent Document 2 has LC oscillator sensor elements with nearly uniform performance characteristics arranged in an array, which makes it possible to obtain not only the sensing results evaluated by the sensor elements, but also data such as their distribution, average, standard deviation, and changes over time.

[0010] Also, Patent Document 3 discloses a sensor IC that uses a sensor element that uses an ion-sensitive field effect transistor (ISFET) having a charge-sensitive component such as a floating gate to evaluate the amount of ions in the liquid on the surface of the sensor IC, and senses the concentration of various analytes in the target liquid.

[0011] The sensor IC described in Patent Document 1 senses the change in the dielectric constant of the liquid. The sensor IC described in Patent Document 3 senses the change in the ion concentration of the liquid. In these sensor ICs, the change in the composition of the bacteria itself before they grow is reflected in the change in dielectric constant or ion concentration. This solves the problem of the time it takes for bacteria to grow, making real-time observation possible. In addition, since the evaluation is performed using a sensor IC that outputs the sensed numerical value, it is possible to perform evaluation over time and with high sensitivity. [Prior art documents] [Patent documents]

[0012] [Patent Document 1] Patent No. 6416398 (registered October 12, 2018) [Patent Document 2] Patent No. 6671063 (registered March 5, 2020) [Patent Document 3] JP 2017-166972 A (Published on September 21, 2017) Summary of the Invention [Problem to be solved by the invention]

[0013] However, the sensor ICs described in Patent Documents 1 and 3 are ICs made of semiconductors and therefore often have a flat configuration. For this reason, a single well is created on a single IC for evaluation, which poses a problem that it is difficult to evaluate a reference culture medium containing only a liquid medium, a culture medium of bacteria without the addition of a drug, a culture medium of bacteria with the addition of a drug, etc. under the same conditions.

[0014] The sensor IC described in Patent Document 2 does not require a well, and bacteria are applied to a solid such as an agar medium, and the agar medium is attached to the surface of the sensor IC for evaluation. However, in order to perform a drug susceptibility test to evaluate a large amount of drugs, multiple agar media must be prepared. Since the sensor IC generally has a small area, in order to prepare multiple agar media, it is necessary to prepare an agar medium that is even smaller than the sensor IC and attach it to the sensor IC, which is not easy to achieve. Thus, it is impossible to use an agar medium to evaluate drug susceptibility taking into account the drug solution concentration for each drug at once.

[0015] An object of one aspect of the present invention is to provide a sensor module capable of evaluating drug susceptibility for each drug at once, taking into account the drug concentration. [Means for solving the problem]

[0016] In order to solve the above problems, a sensor module according to one embodiment of the present invention is characterized in that it comprises a plurality of sensor ICs arranged on a substrate to measure physical properties of a liquid in order to evaluate the drug susceptibility of a drug that inhibits microbial growth, and a plurality of microwells formed on the substrate corresponding to each sensor IC so as to cover the periphery of the surface of each sensor IC in order to contain the liquid to be measured by each sensor IC.

[0017] In order to solve the above problems, another sensor module according to one embodiment of the present invention is characterized in that it comprises a plurality of sensor ICs arranged to cover the other main surface side of a plurality of through holes penetrating from one main surface to the other main surface of a substrate, in order to measure physical properties of a liquid for evaluating drug susceptibility to a drug that inhibits microbial growth, and a plurality of microwells formed by the inner walls of the through holes corresponding to each sensor IC to contain the liquid to be measured by each sensor IC. Effect of the Invention

[0018] According to one aspect of the present invention, drug susceptibility can be evaluated for each drug at once, taking into account the drug concentration. [Brief description of the drawings]

[0019] [Figure 1] FIG. 1 is a perspective view of a sensor module according to a first embodiment. [Diagram 2] 2 is a cross-sectional view taken along the plane A'B' shown in FIG. 1. [Diagram 3] 4 is a cross-sectional view showing a state in which liquid is contained in a microwell formed in the sensor module. FIG. [Figure 4] FIG. 11 is a cross-sectional view showing a state in which liquid overflowing from the microwells is pooled in grooves formed between the microwells. [Diagram 5] 10 is a cross-sectional view showing the relationship between the microwell and a chip component mounted on a substrate on which a sensor IC of the sensor module is formed. FIG. [Figure 6] 2 is a diagram for explaining a configuration of a surface of the sensor IC. FIG. [Figure 7] FIG. 2 is a cross-sectional view showing a state in which a lid is placed on the microwell. [Figure 8] FIG. 11 is a cross-sectional view showing a state in which another lid is placed on the microwell. [Figure 9] FIG. 2 is a plan view illustrating an external shape of the sensor module. [Figure 10] FIG. 11 is a plan view showing a modified example of the sensor module. [Figure 11] FIG. 11 is a plan view showing another modified example of the sensor module. [Figure 12] FIG. 11 is a plan view showing still another modified example of the sensor module. [Figure 13] FIG. 11 is a plan view of a sensor module according to a second embodiment. [Figure 14] FIG. 11 is a plan view showing a modified example of the sensor module. [Figure 15] FIG. 11 is a plan view showing a modified example of the sensor module. [Figure 16] FIG. 11 is a cross-sectional view of a sensor chip provided in a sensor module according to a third embodiment. [Figure 17] 4 is a cross-sectional view of a sensor module on which a plurality of the sensor chips are mounted. FIG. [Figure 18] 11 is a cross-sectional view of the sensor module to which a resin part has been added. FIG. [Figure 19] FIG. 11 is a plan view of a sensor IC according to a fourth embodiment. [Figure 20] 2 is a block diagram showing a schematic configuration of a sensor element formed in the sensor IC. FIG. [Figure 21] 11 is a cross-sectional view showing a procedure for evaluating drug susceptibility on a sensor chip having microwells formed in a sensor IC according to embodiment 5. FIG. [Figure 22] 10 is a cross-sectional view showing a procedure for evaluating drug susceptibility on a sensor chip having microwells formed in the sensor IC. FIG. [Figure 23] 10 is a cross-sectional view showing a procedure for evaluating drug susceptibility on a sensor chip having microwells formed in the sensor IC. FIG. [Figure 24] 10 is a cross-sectional view showing a procedure for evaluating drug susceptibility on a sensor chip having microwells formed in the sensor IC. FIG. [Diagram 25] 10 is a cross-sectional view showing a procedure for evaluating drug susceptibility on a sensor chip having microwells formed in the sensor IC. FIG. [Figure 26] 10 is a cross-sectional view showing a procedure for evaluating drug susceptibility on a sensor chip having microwells formed in the sensor IC. FIG. [Figure 27] 10 is a cross-sectional view showing a procedure for evaluating drug susceptibility on a sensor chip having microwells formed in the sensor IC. FIG. [Figure 28] FIG. 13 is a plan view of a sensor IC provided with an ion-sensitive field effect transistor according to a sixth embodiment. [Figure 29] FIG. 2 is a cross-sectional view of the ion-sensitive field effect transistor. [Diagram 30] FIG. 13 is a cross-sectional view of a sensor module according to a seventh embodiment. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0020] [Embodiment 1] An embodiment of the present invention will be described in detail below. Fig. 1 is a perspective view of a sensor module 1 according to the first embodiment. Fig. 2 is a cross-sectional view taken along the plane A'B' shown in Fig. 1. Fig. 3 is a cross-sectional view showing a state in which test subjects 106A-106B (liquid) are contained in microwells 102A-102B formed in the sensor module 1. Fig. 4 is a cross-sectional view showing a state in which test subjects 106A-106B that have overflowed from the microwells 102A-102B are pooled in a groove 105 formed between the microwells 102A-102B. Fig. 5 is a cross-sectional view showing the relationship between the microwells 102A-102B and a chip component 109 (electronic component) mounted on a substrate 100 on which sensor ICs 103A-103F of the sensor module 1 are formed.

[0021] The sensor module 1 comprises six sensor ICs 103A-103F arranged in two rows and three columns on a substrate 100 for measuring physical properties of a liquid in order to evaluate drug susceptibility to a drug that inhibits microbial growth, and six microwells 102A-102B formed in two rows and three columns on the substrate 100 corresponding to each of the sensor ICs 103A-103F so as to cover the peripheral edges of the surface of each of the sensor ICs 103A-103F and to accommodate test specimens 106A-106B (liquids) to be measured by each of the sensor ICs 103A-103F.

[0022] In this embodiment, an example in which six sensor ICs 103A to 103F are mounted on one sensor module 1 will be described, but the number of sensor ICs to be mounted can be set to the number required for the target drug susceptibility test, etc., so that the sensor ICs can be mounted efficiently and flexibly to meet the needs. The number of sensor ICs may be any number as long as it is more than one.

[0023] The sensor module 1 further includes a groove 105 formed between adjacent microwells 102A and 102B to prevent contamination of the test object 106A contained in the microwell 102A with the test object 106B contained in the microwell 102B.

[0024] The sensor module 1 further includes a chip component 109 mounted on the substrate 100. The microwells 102A and 102B are formed to cover the chip component 109.

[0025] The heights of the microwells 102A and 102B from the substrate 100 are equal to each other.

[0026] The sensor module 1 is controlled by communication with an external control unit 110 .

[0027] Each of the sensor ICs 103A to 103F is connected to wiring on the substrate 100 via, for example, a number of wire bonds 104A-104B for power supply and external communication. For external communication and connection to a power source, a connector (not shown) or the like connected to the wiring on the substrate 100 is used to exchange data with an external control unit 110.

[0028] A resin part 101 formed integrally with the microwells 102A and 102B is placed on the substrate 100. This resin part 101 is formed so as to cover the substrate 100, the periphery of the surfaces of the sensor ICs 103A-103F, and the wire bonds 104A-104B. The resin part 101 is placed to prevent contact between the test objects 106A-106B, which will be described later, and the wire bonds 104A, 104B, and to increase the rigidity of the sensor module 1.

[0029] In this embodiment, the surfaces of the sensor ICs 103A-103F are not covered with microwells 102A-102B except for the periphery. This is because sensor elements 108, which will be described later, are disposed on the surfaces of the sensor ICs 103A-103F. Wells 102A-102B are formed on the periphery of the surfaces of the sensor ICs 103A-103F. These wells 102A-102B are provided to hold test objects 106A-106B on the sensor ICs 103A-103F. Grooves 105 are formed between the wells 102A-102B.

[0030] Appropriate amounts of the test objects 106A and 106B are injected into the wells 102A and 102B as shown in Fig. 3. Then, the characteristics of the test objects 106A and 106B are evaluated by sensor elements 108 (Figs. 6 and 20) formed in the sensor ICs 103A to 103F.

[0031] 4, if the test objects 106A and 106B overflow from the wells 102A and 102B due to injection of too much test objects 106A and 106B into the wells 102A and 102B, the overflowing test objects 106A and 106B are collected in the groove 105 as test objects 107. Therefore, the test object 106A contained in the well 102A and the test object 106B contained in the well 102B do not mix with each other. This makes it possible to prevent contamination of the solutions of the test objects 106A and 106B.

[0032] Furthermore, since the resin portion 101 is formed on the substrate 100 so as to cover the wire bonds 104A, 104B and the chip components 109, it is possible to prevent the test objects 106A, 106B spilling out of the wells 102A, 102B from coming into contact with the wire bonds 104A, 104B and the chip components 109.

[0033] 6 is a diagram for explaining the configuration of the surfaces of the sensor ICs 103A and 103B. The sensor IC 103A has a plurality of sensor elements 108 that sense the physical properties of the test object 106A, and a control circuit 111 for controlling the plurality of sensor elements 108. The sensor IC 103A forms a sensor array in which N sensor elements 108 are arranged on an array.

[0034] Sensor ICs 103B to 103F are configured similarly to sensor IC 103A.

[0035] The sensor module 1 further includes an external control unit 110 that communicates with each control circuit 111 via a bus 112 to obtain data representing the physical properties of the test objects 106A-106 sensed by the sensor elements 108.

[0036] Each control circuit 111 includes a serial bus interface such as I2C, controls each sensor element 108, acquires data, transfers data, and communicates with an external control unit 110 via a bus 112. The external control unit 110 assigns a unique address to each of the sensor ICs 103A-103F, and acquires data of the sensor elements 108 provided in each of the sensor ICs 103A-103F by performing serial communication by specifying the unique address.

[0037] 7 is a cross-sectional view showing the state in which the lid 120 is placed on the microwells 102A-102B. The lid 120 is used to prevent the test objects 106A-106B from evaporating while the physical properties of the test objects 106A-106B are measured over a long period of time. In this case, since the lid 120 is plate-shaped, it is desirable that the heights of the wells 102A-102B from the substrate 100 be uniform.

[0038] Fig. 8 is a cross-sectional view showing another lid 121 placed on the microwells 102A-102B. As shown in Fig. 8, the lid 121 may be formed so as to protrude toward and come into contact with the upper surfaces of the test objects 106A-106B. In this case as well, it is convenient to form the lid 121 if the heights of the wells 102A-102B from the substrate 100 are uniform.

[0039] 9 is a plan view for explaining the external shape of the sensor module 1. The external shape of the substrate 100 of the sensor module 1 is configured with short sides measuring 20 mm to 30 mm and long sides measuring 70 mm to 80 mm. Therefore, the sensor module 1 can be set on a stage for placing a sample of an upright optical microscope that uses a general slide glass. Therefore, the sensor module 1 has optimal dimensions for observation from above with an upright optical microscope, making it highly versatile.

[0040] Fig. 10 is a plan view showing a modified example of the sensor module 1. Fig. 11 is a plan view showing another modified example of the sensor module 1. Fig. 12 is a plan view showing yet another modified example of the sensor module 1.

[0041] In the sensor module 1 described above, as shown in Fig. 9, an example is shown in which the outer and inner peripheries of the wells 102A and 102B are formed in a square shape, but as shown in Fig. 10, the outer and inner peripheries of the wells 102A and 102B may be formed in a circular shape. Also, as shown in Fig. 11, the wells 102A and 102B may be formed with rounded corners on the inner periphery. Furthermore, as shown in Fig. 12, in addition to the inner corners, the outer corners may also be formed in a rounded shape.

[0042] [Embodiment 2] Other embodiments of the present invention will be described below. For ease of explanation, the same reference numerals are given to members having the same functions as those described in the above embodiment, and the description thereof will not be repeated.

[0043] FIG. 13 is a plan view of a sensor module 1A according to a second embodiment. The sensor ICs 103A to 103F according to the first embodiment have been described as being configured by arranging the same sensor elements 108 in an array shape. In the sensor module 1A according to the second embodiment, as shown in FIG. 13, different types of sensor elements 108, 108a, 108b, 108c, and 108d are arranged in an array shape to configure each sensor IC. For example, in the example shown in FIG. 13, three sensor ICs in which a plurality of sensor elements 108 are arranged in an array are arranged in the leftmost column. Then, three sensor ICs in which a plurality of sensor elements 108a are arranged in an array are arranged in the second column from the left. Then, three sensor ICs in which a plurality of sensor elements 108b are arranged in an array are arranged in the third column from the left, three sensor ICs in which a plurality of sensor elements 108c are arranged in an array are arranged in the fourth column from the left, and three sensor ICs in which a plurality of sensor elements 108d are arranged in an array are arranged in the rightmost column.

[0044] In this manner, the sensor ICs, each having different sensor elements 108, 108a, 108b, 108c, and 108d arranged therein, are arranged in five rows (the arrangement is not limited to five rows). In this case, since five different types of sensor ICs exist in the sensor module 1A, when checking the same change over time in the test object at the same time, for example, it is possible to measure the change in dielectric constant in the test object in the row of sensor elements 108 and to measure the change in ion sensitivity in the test object in the row of sensor elements 108a. This makes it possible to obtain composite information about the test object from different perspectives.

[0045] 14 and 15 are plan views showing modified examples of the sensor module 1A. A plurality of different types of sensor elements may be arranged on one sensor IC. For example, in the example shown in Fig. 14 and Fig. 15, a plurality of sensor elements 108 and a plurality of sensor elements 108a are arranged on one sensor IC.

[0046] In this case, multiple pieces of compound information on drug susceptibility testing can be obtained for the test specimen under the same evaluation conditions in the same well, which makes it possible to identify new characteristics of the microorganism.

[0047] [Embodiment 3] Further, for the sake of convenience, the same reference numerals are given to the members having the same functions as those described in the above embodiment, and the description thereof will not be repeated.

[0048] Fig. 16 is a cross-sectional view of the sensor chip 10 provided in the sensor module 1B according to embodiment 3. Fig. 17 is a cross-sectional view of the sensor module 1B on which a plurality of sensor chips 10 are mounted. Fig. 18 is a cross-sectional view of the sensor module 1B to which a resin part 101 is added.

[0049] The sensor module 1B includes a plurality of sensor chips 10 mounted on a substrate 100. Each sensor chip 10 includes a sensor IC 103, a plurality of electrodes 118 mounted on the substrate 100, a plurality of wire bonds 114 connecting the surface of the sensor IC 103 to the electrodes 118, and a microwell 102 formed to cover the periphery of the surface of the sensor IC 103, the plurality of wire bonds 114, and the plurality of electrodes 118. In this manner, the sensor chip 10 is configured so that a solution of the test subject can be contained on the surface of the sensor IC 103 in the microwell 102.

[0050] In this way, a single sensor module 1B can be equipped with a plurality of sensor chips 10. The number of sensor chips 10 to be mounted can be set to the number required for the target drug susceptibility test or the like, so that the sensor ICs 103 can be mounted and handled efficiently and flexibly.

[0051] 18, resin parts 101 may be added between the microwells 102 of the sensor chip 10 on the substrate 100. This prevents a test object such as a liquid (not shown) from directly contacting the substrate 100 even if the test object overflows from the microwells 102, thereby reducing the risk of electrical leakage.

[0052] [Embodiment 4] Further, for the sake of convenience, the same reference numerals are given to the members having the same functions as those described in the above embodiment, and the description thereof will not be repeated.

[0053] (Configuration of sensor element 108) Fig. 19 is a plan view of the sensor IC 103 according to embodiment 4. Fig. 20 is a block diagram showing a schematic configuration of a sensor element 108 formed in the sensor IC 103.

[0054] The sensor IC 103 corresponds to the above-mentioned sensor ICs 103A to 103F. The sensor element 108 of the above-mentioned sensor ICs 103A to 103F can be configured by an oscillation circuit 130. The oscillation circuit 130 includes a differential circuit 19 and a resonator 13 including an inductor 14 and a capacitor 15.

[0055] The oscillator circuit 130 changes the oscillation frequency according to the physical property (dielectric constant) of the test object, and functions as a sensor section that senses the physical property. The resonator 13 is an LC circuit formed between the differential inputs of the differential circuit 19. The differential circuit 19 may be a known differential circuit, such as a differential circuit made of cross-coupled transistors. The sensor IC 103 can obtain a distribution map of the evaluation results of the physical property of the test object on the surface of the sensor IC 103 by arranging the oscillator circuits 130, which are the sensor elements 108, in an array.

[0056] [Embodiment 5] Further, for the sake of convenience, the same reference numerals are given to the members having the same functions as those described in the above embodiment, and the description thereof will not be repeated.

[0057] 21 to 27 are cross-sectional views showing the procedure for performing drug susceptibility assessment on a sensor chip 10 in which microwells 102 are formed in a sensor IC 103. For simplicity, a case will be described in which drug susceptibility assessment is performed on a sensor chip 10 in which microwells 102 are formed in a sensor IC 103 shown in FIG.

[0058] First, a reference liquid 116A containing bacteria is injected into a well 102 as shown in FIG. 22. Next, a drug A is administered to the reference liquid 116A to generate a mixed solution 116B as shown in FIG. 23. Then, after confirming that the ambient temperature and state of the mixed solution 116B have stabilized, it is evaluated as an initial state. In the case of the oscillator circuit 130 which is the sensor element 108 shown in FIG. 20, the oscillation frequency of each effective oscillator circuit 130 is recorded. From this initial state, bacteria on which the drug A has no effect are multiplying, so as time passes, the effect of the drug A can be confirmed.

[0059] Fig. 24 shows an example in which bacterial growth is suppressed by drug A. In this case, even after several hours and days, the solution 116C does not change much from the solution 116B, so the oscillation frequency when the solution 116C is evaluated by the oscillation circuit 130 shown in Fig. 20 does not differ significantly from the oscillation frequency of the oscillation circuit 130 when the solution 116B in Fig. 23 is evaluated. Therefore, it is determined that the drug A is effective in suppressing bacterial growth.

[0060] Next, an example of uncontrolled bacterial growth is given.

[0061] First, the reference liquid 116A containing bacteria is injected into the well 102 as shown in FIG. 25, and then the drug B is administered to the reference liquid 116A to generate the mixed solution 117B as shown in FIG. 26. Then, after confirming that the ambient temperature and state of the mixed solution 117B are stable, it is evaluated as an initial state. Next, after several hours and days have passed, the solution 117C shows a large change compared to the solution 117B due to bacterial growth, and the oscillation frequency evaluated by the oscillation circuit 130 shown in FIG. 20 shows a large difference from the oscillation frequency of the oscillation circuit 130 that evaluated the mixed solution 117B in FIG. 26. It is determined that the drug B administered onto the sensor IC 103 including the oscillation circuit 130 in which the difference in the oscillation frequencies of the two mixed solutions 117B and 117C is larger than the frequency determined in advance by experiments cannot suppress the bacterial growth.

[0062] [Embodiment 6] Further, for the sake of convenience, the same reference numerals are given to the members having the same functions as those described in the above embodiment, and the description thereof will not be repeated.

[0063] Fig. 28 is a plan view of a sensor IC 103 provided with an ion-sensitive field effect transistor (ISFET) 131 according to embodiment 6. Fig. 29 is a cross-sectional view of the ISFET 131.

[0064] The multiple sensor elements 108 arranged in an array in the sensor IC 103 may be multiple ISFETs 131 that detect the amount of specific ions in the liquid. The ISFET 131 that serves as the sensor element 108 is a sensor that selectively responds to specific ions in the liquid and generates an electrode potential corresponding to the concentration of the specific ions in a gate electrode 132. The ISFET 131 can detect the amount of specific ions in the liquid by detecting the value of a current that flows through a channel 135 between a source electrode 133 and a drain electrode 134.

[0065] By arranging a plurality of ISFETs 131 in an array on the sensor IC 103, a distribution map of the evaluation results on the surface of the sensor IC 103 can be obtained.

[0066] [Embodiment 7] Fig. 30 is a cross-sectional view of a sensor module 1C according to embodiment 7. Fig. 30 shows a cross-section of another example of the sensor ICs 103A and 103B taken along the plane A'B' shown in Fig. 1.

[0067] The sensor module 1C includes a plurality of sensor ICs 103A-103B arranged to cover the other main surface side of a plurality of through holes 136 penetrating from one main surface to the other main surface of the substrate 100C, in order to measure physical properties of a liquid for evaluating drug susceptibility to a drug that inhibits microbial growth, and a plurality of microwells 102C-102D formed by the inner walls of the through holes 136 corresponding to each sensor IC 103A-103B to contain the liquid to be measured by each sensor IC 103A-103B.

[0068] In the sensor module 1C, through holes 136 are opened in the substrate 100C, and the sensor ICs 103A and 103B are mounted on the back side of the substrate 100C with multiple bumps 141 so as to cover the through holes 136. The bumps 141 are then filled with underfill 142 made of resin or the like to prevent water from entering the bumps 141. The microwells 102A and 102B formed in the sensor module 1C become the through holes 136 opened in the substrate 100C. Walls 143 made of resist or the like are arranged around the through holes 136 that will become the microwells 102A and 102B so as to surround the through holes 136, forming grooves 105 between the microwells 102C and 102D. When a test subject (liquid) not shown is placed in the microwells 102C·102D, even if the test subject overflows from the microwells 102C·102D, the test subject can be collected in the groove 105 formed between the microwells 102C·102D.

[0069] 〔summary〕 The sensor modules 1, 1A, 1B of the present invention according to aspect 1 comprise a plurality of sensor ICs 103, 103A-103F arranged on a substrate 100 for measuring the physical properties of a liquid (test specimens 106A-106B) for evaluating the drug susceptibility of a drug that inhibits the growth of microorganisms, and a plurality of microwells 102, 102A, 102B formed on the substrate 100 corresponding to each of the sensor ICs 103, 103A-103F so as to cover the peripheral edge of the surface of each of the sensor ICs 103, 103A-103F and to contain the liquid (test specimens 106A-106B) to be measured by each of the sensor ICs 103, 103A-103F.

[0070] According to this feature, a plurality of sensor ICs for measuring the physical properties of a liquid to evaluate drug susceptibility to a drug that inhibits the proliferation of microorganisms are arranged on a substrate. Then, a plurality of microwells covering the periphery of the surface of each sensor IC are formed on the substrate corresponding to each sensor IC to accommodate the liquid to be measured by each sensor IC. Therefore, a plurality of types of liquids containing a plurality of types of drugs and microorganisms to be measured can be accommodated in a plurality of microwells corresponding to a plurality of sensor ICs. Therefore, drug susceptibility can be evaluated at once for each drug, taking into account the drug solution concentration.

[0071] It is preferable that the sensor modules 1, 1A, and 1B according to aspect 2 of the present invention, in aspect 1 above, further comprise a groove 105 formed between adjacent microwells 102A and 102B to prevent mixing of a liquid (test object 106A) contained in one of the plurality of microwells (microwell 102A) with a liquid (test object 106B) contained in another of the plurality of microwells (microwell 102B).

[0072] According to the above configuration, liquid that overflows from the microwells can be collected in the groove.

[0073] It is preferable that the sensor modules 1, 1A, and 1B according to aspect 3 of the present invention further include, in aspect 1 above, an electronic component (chip component 109) mounted on the substrate 100, and that the microwells 102, 102A, and 102B are formed so as to cover the electronic component (chip component 109).

[0074] According to the above configuration, it is possible to prevent the liquid spilling out of the microwells from coming into contact with the electronic components.

[0075] In the sensor modules 1, 1A, and 1B of aspect 4 of the present invention, in aspect 1 above, it is preferable that the substrate 100 has electrodes 118 formed on its surface, and further includes wire bonds 104A, 104B connecting the surfaces of the sensor ICs 103, 103A-103F to the electrodes 118, and the microwells 102, 102A, and 102B are formed to cover the wire bonds 104A, 104B.

[0076] According to the above configuration, it is possible to prevent the liquid spilling out of the microwells from coming into contact with the wire bonds.

[0077] In the sensor modules 1, 1A, and 1B of aspect 5 of the present invention, in the above-mentioned aspect 1, each of the sensor ICs 103, 103A to 103F has a plurality of sensor elements 108 that sense the physical properties of the liquid (test objects 106A and 106B) and a control circuit 111 for controlling the plurality of sensor elements 108, and preferably further includes an external control unit 110 that communicates with each control circuit 111 to obtain data representing the physical properties of the liquid (test objects 106A and 106B) sensed by the sensor elements 108.

[0078] According to the above configuration, the physical properties of the liquid for evaluating drug susceptibility to a drug that inhibits the proliferation of microorganisms can be measured by a plurality of sensor elements.

[0079] In the sensor modules 1, 1A, and 1B according to a sixth aspect of the present invention, in the above-mentioned first aspect, it is preferable that the heights of the plurality of microwells 102, 102A, and 102B are equal to each other.

[0080] According to the above configuration, a lid for preventing evaporation of liquid during long-term measurement can be provided with a simple structure.

[0081] In the sensor modules 1, 1A, and 1B according to a seventh aspect of the present invention, in the above-mentioned first aspect, it is preferable that the substrate 100 is formed in a rectangular shape with short sides of 20 mm to 30 mm and long sides of 70 mm to 80 mm.

[0082] According to the above configuration, the substrate has an optimum size for observation under a microscope, and the versatility of the sensor module is increased.

[0083] The sensor modules 1 / 1A / 1B of aspect 8 of the present invention are preferably such that, in aspect 5 above, the physical properties of the liquid (test objects 106A / 106B) include a first physical property and a second physical property, and a portion of the sensor elements 108 of the plurality of sensor ICs 103, 103A-103F are sensor elements configured to measure the first physical property of the liquid, and another portion of the sensor elements 108 of the plurality of sensor ICs 103, 103A-103F are sensor elements configured to measure the second physical property of the liquid (test objects 106A / 106B).

[0084] According to the above configuration, since the first physical property and the second physical property can be measured, it is possible to obtain composite information about the liquid from different viewpoints.

[0085] The sensor modules 1 / 1A / 1B of aspect 9 of the present invention are preferably configured in such a manner that, in aspect 5 above, the physical properties of the liquid (objects under test 106A / 106B) include a first physical property and a second physical property, and some of the multiple sensor elements 108 of the sensor ICs 103, 103A-103F are sensor elements configured to measure the first physical property of the liquid (objects under test 106A / 106B), and other some of the multiple sensor elements 108 are sensor elements configured to measure the second physical property of the liquid (objects under test 106A / 106B).

[0086] According to the above configuration, multiple pieces of composite information related to drug susceptibility tests can be obtained for liquids in the same microwell under the same evaluation conditions, which makes it possible to identify new characteristics of microorganisms.

[0087] In the sensor modules 1, 1A, and 1B according to aspect 10 of the present invention, in the above-mentioned aspect 9, it is preferable that the first physical property includes a dielectric constant of the liquid (test objects 106A and 106B) and the second physical property includes ion sensitivity of the liquid (test objects 106A and 106B).

[0088] According to the above configuration, since the dielectric constant and the ion sensitivity can be measured, composite information of the liquid can be obtained from different perspectives.

[0089] In the sensor modules 1 / 1A / 1B according to aspect 11 of the present invention, in the above-mentioned aspect 5, it is preferable that the sensor element 108 includes at least one of an oscillator circuit 130 that changes the oscillation frequency in accordance with the dielectric constant of the liquid (test objects 106A / 106B) and an ion-sensitive field effect transistor 131 that detects specific ions in the liquid (test objects 106A / 106B).

[0090] According to the above configuration, at least one of the dielectric constant and the ion sensitivity can be measured.

[0091] The sensor module of aspect 12 of the present invention comprises a plurality of sensor ICs 103A-103B arranged to cover the other main surface side of a plurality of through holes 136 penetrating from one main surface to the other main surface of a substrate 100C, in order to measure physical properties of a liquid for evaluating drug susceptibility to a drug that inhibits microbial growth, and a plurality of microwells 102C-102D formed by the inner walls of the through holes 136 corresponding to each sensor IC 103A-103B to contain the liquid to be measured by each sensor IC 103A-103B.

[0092] According to this feature, a plurality of sensor ICs for measuring the physical properties of a liquid for evaluating drug susceptibility to a drug that inhibits the proliferation of microorganisms are arranged to cover the other main surface side of a plurality of through holes penetrating from one main surface to the other main surface of the substrate. Then, a plurality of microwells are formed by the inner walls of the through holes corresponding to each sensor IC to accommodate the liquid to be measured by each sensor IC. Therefore, a plurality of types of liquids containing a plurality of types of drugs and microorganisms to be measured can be accommodated in a plurality of microwells corresponding to a plurality of sensor ICs. Therefore, drug susceptibility can be evaluated at once for each drug, taking into account the drug solution concentration.

[0093] The present invention is not limited to the above-described embodiments, and various modifications are possible within the scope of the claims. Embodiments obtained by appropriately combining the technical means disclosed in different embodiments are also included in the technical scope of the present invention. [Explanation of symbols]

[0094] 1 Sensor module 100 Substrates 103, 103A~103F Sensor IC 102, 102A, 102B, 102C, 102D Microwells 104A Wirebond 104B Wirebond 105 Groove 106A Test object (liquid) 106B Test object (liquid) 108 Sensor element 109 Chip parts (electronic parts) 110 External control unit 111 Control circuit 118 Electrode 130 Oscillator circuit (sensor element) 131 Ion-sensitive field effect transistor (sensor element) 136 Through hole

Claims

1. A plurality of sensor ICs arranged on a substrate for measuring physical properties of a liquid for evaluating drug susceptibility to a drug that inhibits the growth of microorganisms; a plurality of microwells formed on the substrate corresponding to each of the sensor ICs so as to cover the periphery of a surface of each of the sensor ICs in order to contain the liquid to be measured by each of the sensor ICs; A sensor module, characterized in that the sensor IC corresponding to each of the plurality of microwells has a plurality of sensor elements for sensing the physical properties of the liquid.

2. 2. The sensor module according to claim 1, further comprising a groove formed between adjacent microwells to prevent liquid contained in one of the plurality of microwells from mixing with liquid contained in another of the plurality of microwells.

3. Further comprising electronic components mounted on the substrate; The sensor module according to claim 1 , wherein the microwell is formed so as to cover the electronic component.

4. the substrate having an electrode formed on a surface thereof; a wire bond connecting a surface of the sensor IC to the electrode; The sensor module of claim 1 , wherein the microwell is formed over the wire bond.

5. Each sensor IC has a control circuit for controlling the plurality of sensor elements, The sensor module of claim 1 , further comprising an external controller that communicates with each control circuit to obtain data representative of the physical properties of the liquid sensed by the sensor elements.

6. The sensor module according to claim 1 , wherein the heights of the microwells are equal to each other.

7. 2. The sensor module according to claim 1, wherein the substrate is formed in a rectangular shape with short sides of 20 mm to 30 mm and long sides of 70 mm to 80 mm.

8. the physical properties of the liquid include a first physical property and a second physical property; 6. The sensor module according to claim 5, wherein a portion of the sensor elements among the plurality of sensor ICs are sensor elements configured to measure a first physical property of the liquid, and another portion of the sensor elements among the plurality of sensor ICs are sensor elements configured to measure a second physical property of the liquid.

9. the physical properties of the liquid include a first physical property and a second physical property; 6. The sensor module according to claim 5, wherein a portion of the plurality of sensor elements of the sensor IC are sensor elements configured to measure a first physical property of the liquid, and another portion of the plurality of sensor elements are sensor elements configured to measure a second physical property of the liquid.

10. the first property comprises a dielectric constant of the liquid; 10. The sensor module according to claim 8 or 9, wherein the second property includes ion sensitivity of the liquid.

11. 2. The sensor module according to claim 1, wherein the sensor element includes at least one of an oscillator circuit that changes an oscillation frequency in response to the dielectric constant of the liquid, and an ion-sensitive field effect transistor that detects specific ions in the liquid.

12. A plurality of sensor ICs are arranged to cover the other main surface side of a plurality of through holes penetrating from one main surface to the other main surface of the substrate, in order to measure physical properties of a liquid for evaluating drug susceptibility to a drug that inhibits the growth of microorganisms; a plurality of microwells formed by inner walls of the through holes corresponding to the respective sensor ICs to accommodate the liquid to be measured by each sensor IC; A sensor module, characterized in that the sensor IC corresponding to each of the plurality of microwells has a plurality of sensor elements for sensing the physical properties of the liquid.

13. A method for measuring the physical properties of a liquid for evaluating the drug susceptibility of a drug that inhibits the growth of microorganisms, comprising: a plurality of sensor ICs arranged on a substrate; a plurality of microwells formed on the substrate corresponding to each of the sensor ICs so as to cover the periphery of a surface of each of the sensor ICs in order to contain the liquid to be measured by each of the sensor ICs; Each sensor IC includes a plurality of sensor elements for sensing a physical property of the liquid; a control circuit for controlling the plurality of sensor elements; A sensor module further comprising an external control unit that communicates with each control circuit to obtain data representative of the physical properties of the liquid sensed by the sensor elements.

14. The physical properties of the liquid include a first physical property and a second physical property, The sensor module according to claim 13, wherein a portion of the sensor elements among the plurality of sensor ICs are sensor elements configured to measure a first physical property of the liquid, and another portion of the sensor elements among the plurality of sensor ICs are sensor elements configured to measure a second physical property of the liquid.

15. The physical properties of the liquid include a first physical property and a second physical property, The sensor module according to claim 13, wherein a portion of the plurality of sensor elements of the sensor IC are sensor elements configured to measure a first physical property of the liquid, and another portion of the plurality of sensor elements are sensor elements configured to measure a second physical property of the liquid.

16. The method of claim 1, wherein the first property comprises a dielectric constant of the liquid.

16. The sensor module according to claim 14 or 15, wherein the second property comprises ion sensitivity of the liquid.

17. The sensor element includes an oscillator circuit that changes an oscillation frequency in response to the dielectric constant of the liquid; The sensor module according to claim 13, further comprising at least one of an ion-sensitive field effect transistor for detecting specific ions in the liquid.

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