Bacteriological examination device and bacteriological examination system

Abstract

To detect, in a short time, a change in the dielectric constant of liquid including bacteria.SOLUTION: A bacteriological examination device (1) comprises a plurality of oscillation circuits (6) that are arranged in a well (5) and whose oscillatory frequency changes according to a change in the dielectric constant of a body to be examined (8). A sensing area in which the change in dielectric constant can be detected in correspondence with the oscillation circuits (6) has dimensions of X μm, Y μm, and Z μm. The number N of the oscillation circuits (6) satisfies N≥log(0.001) 107 / (X Y Z).SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present invention is directed to a method for measuring the dielectric constant or Bacteria equipped with a sensor IC (Integrated Circuit) that detects changes in dielectric constant The present invention relates to an inspection device and a bacterial inspection system. [Background technology]

[0002] A plurality of oscillator circuits that function as sensors are arranged on the same plane on the surface of a semiconductor integrated circuit. The dielectric constant of each part of the object to be detected that exists near the surface of the semiconductor integrated circuit is changed. A sensor IC that observes the in-plane distribution of oxidation is known in the prior art (Patent Document 1, Non-Patent Document 2). Reference 1). [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Patent No. 6486740 (registered March 1, 2019) [Non-patent literature]

[0004] [Non-Patent Document 1] T.Mitsunaka, et.al, “CMOS Biosensor IC Focusing on Dielectric Relaxations of Biological Water with 120-GHz and 60-GHz Oscillator Arrays”, JSSC Summary of the Invention [Problem to be solved by the invention]

[0005] However, the above-mentioned conventional technology has the following problems. FIG. 9 is a plan view showing the structure of the device for explaining the operation of a conventional bacterial testing device. FIG.

[0006] The conventional bacteria testing device includes a semiconductor integrated circuit 94 formed on a printed wiring board, A circular portion of the surface of the semiconductor integrated circuit 94 is exposed on the semiconductor integrated circuit 94. A well 95 is formed to hold a liquid containing bacteria 98 to be tested, and a half-well in the well 95 The conductors are arranged alternately (staggered) in the integrated circuit 94 to function as sensors. and a plurality of oscillation circuits 96 whose oscillation frequency changes in response to a change in the dielectric constant of the liquid.

[0007] For each of the plurality of oscillation circuits 96, a sensing region capable of detecting the change in the dielectric constant is provided. The area is located above each of the plurality of oscillator circuits 96 in the liquid, and the area is shaped like each of the oscillator circuits 96. In this conventional bacterial testing device, as shown in Figure 8, When the concentration of bacteria 98 is low, there is a high probability that bacteria 98 are not present above the sensing area. For this reason, we cultivated bacteria 98 over time, and as shown in Figure 9, we observed that bacteria 98 sensed The change in dielectric constant can be detected only after the colony 98A (bacteria population) grows to cover the area. Therefore, in this conventional detection method, it takes time for bacteria98 to grow in order to detect the change in dielectric constant. In addition, when the concentration of bacteria is low, the change in the dielectric constant cannot be quantified. There are challenges.

[0008] One aspect of the present invention is to detect, in a short time, a change in the dielectric constant of a liquid containing bacteria to be inspected. This is a bacterial test that can detect changes in dielectric constant even when the bacterial concentration is low. The object is to realize a device and a bacterial testing system. [Means for solving the problem]

[0009] In order to solve the above problems, a bacterial testing device according to one aspect of the present invention is a semiconductor integrated a circuit formed on the semiconductor integrated circuit so as to expose a portion of the surface of the semiconductor integrated circuit; a well for holding a liquid to be inspected, and the semiconductor integrated circuit in the well. a plurality of oscillation circuits arranged in the liquid, the oscillation frequency of which changes in response to a change in the dielectric constant of the liquid; a sensing element capable of detecting the change in the dielectric constant, corresponding to each of the plurality of oscillation circuits; The oscillation circuit is disposed in the semiconductor integrated circuit in each well. The number of the elements is 231 or more.

[0010] In order to solve the above problems, another bacterial testing device according to one aspect of the present invention is a semiconductor an integrated circuit; and a semiconductor integrated circuit mounted on the semiconductor integrated circuit so as to expose a portion of the surface of the semiconductor integrated circuit. a well formed in the semiconductor integrated circuit for holding a liquid to be inspected; a plurality of oscillation circuits arranged in the path, the oscillation frequency of which changes with the change in the dielectric constant of the liquid; a sensor capable of detecting the change in dielectric constant corresponding to each of the plurality of oscillation circuits; A sensing region is present in the liquid, and the sensing region is along the surface of the semiconductor integrated circuit. The dimensions X μm and Y μm in the directions intersecting each other and the dimensions Y μm in the directions intersecting the surface of the semiconductor integrated circuit The number of the oscillator circuits is N, and N is N≧1. og(0.001)·10 7 / (X·Y·Z).

[0011] In order to solve the above problems, a bacterial testing system according to one aspect of the present invention is A bacterial testing device according to the embodiment and a housing that holds the bacterial testing device therein, The housing has a temperature controller for controlling the temperature of a space containing the bacterial testing device held therein. It is characterized by having a controller. [Effects of the Invention]

[0012] According to one aspect of the present invention, a change in the dielectric constant of a liquid containing bacteria to be inspected can be detected in a short time. Furthermore, the change in the dielectric constant can be detected even when the bacterial concentration is low. [Brief explanation of the drawings]

[0013] [Figure 1] FIG. 1 is a perspective view showing a schematic configuration of a bacteria testing device according to a first embodiment. [Figure 2] FIG. 2 is a plan view of a main part of the bacteria testing device. [Figure 3] FIG. 2 is a block diagram showing a schematic configuration of a sensor circuit provided in the bacteria testing device. [Figure 4] FIG. 10 is a cross-sectional view showing the positional relationship between a part of a semiconductor integrated circuit provided in the bacteria testing device and a test object. [Figure 5] FIG. 10 is a perspective view showing a schematic configuration of a bacteria testing device according to a third embodiment. [Figure 6] FIG. 10 is a perspective view showing the schematic configuration of a bacterial testing system according to a fourth embodiment. [Figure 7] FIG. 10 is a perspective view showing a schematic configuration of another bacterial testing system according to the fourth embodiment. [Figure 8] FIG. 1 is a plan view showing the configuration of a conventional bacteria testing device. [Figure 9] FIG. 10 is a plan view for explaining the operation of the bacteria testing device. DETAILED DESCRIPTION OF THE INVENTION

[0014] [Embodiment 1] Hereinafter, one embodiment of the present invention will be described in detail.

[0015] Multiple oscillator circuits function as sensors for detecting bacteria in samples with various bacterial concentrations. As a result of conducting detection experiments by changing the number of bacteria in the specimen, the number of bacteria in the specimen The number of colonies (bacterial population) is 10 per mL. 5 pieces (10 5 CFU / ml, CFU is Colon If there are more than one oscillator circuits, at least one oscillator circuit can be generated. Experiments have confirmed that bacteria can be detected using a vibration circuit.

[0016] Also, 10 5 For samples with a concentration around CFU / ml, each sensor judges the presence or absence of bacteria as 1 / 0. If the number of sensors that show a positive result of 1 is measured, the bacterial concentration of the sample can be quantified. It was.

[0017] A detailed embodiment will be described below with reference to FIGS.

[0018] (Overall configuration of bacteria testing device 1) FIG. 1 is a perspective view showing a schematic configuration of a bacterial testing device 1 according to the first embodiment. The device 1 includes a printed wiring board 20. On the printed wiring board 20, a semiconductor device is An integrated circuit 4 and a frequency detection circuit 18 are implemented.

[0019] The well 5 for holding the liquid to be tested by the bacteria testing device 1 is The well is formed on the semiconductor integrated circuit 4 so as to expose a circular portion of the surface. 5 is made of, for example, PDMS (polydimethylsiloxane).

[0020] 2 is a plan view of the essential parts of the bacteria testing device 1. The inside of the circle indicating the position of the inner periphery of the well 5 This is the area where the surface of the semiconductor integrated circuit 4 comes into contact with the liquid to be inspected. On the surface of the semiconductor integrated circuit 4, a total of 256 oscillator circuits 6 are arranged in a matrix of 16×16. Of the 256 oscillator circuits 6, 232 are filled in. The oscillator circuit 6 is disposed inside the inner circumferential surface of the well 5, so that the liquid to be inspected It is an oscillator circuit that is effective for testing to detect changes in the dielectric constant of liquids.

[0021] On the other hand, the 16 oscillator circuits 6 at the four unfilled corners are located on the inner circumferential surface of the well 5. Since it is not located inside, it is not an effective oscillator circuit for testing.

[0022] Therefore, by using 232 effective oscillator circuits 6, the amount of the vibrations contained in the liquid contained in the well 5 can be reduced. It is possible to realize the detection of bacteria that are present in the sample. It is not necessary to create an oscillator circuit, and even if it is created, the output of the invalid oscillator circuit does not have to be subject to inspection. stomach.

[0023] (Configuration of sensor circuit 12) FIG. 3 is a block diagram showing a schematic configuration of the sensor circuit 12 provided in the bacteria testing device 1. The sensor circuit 12 includes a plurality of oscillator circuits 6 and a plurality of oscillator circuits 6 connected to each of the oscillator circuits 6. a plurality of frequency divider circuits 16; a multiplexer 17 connected to the plurality of frequency divider circuits 16; and a frequency detection circuit 18 connected to the duplexer 17.

[0024] Here, the oscillation circuit 6 and the multiplexer 17 are formed in the semiconductor integrated circuit 4. However, the frequency divider circuit 16 and the frequency detector circuit 18 are located in the same semiconductor integrated circuit 4 as the oscillator circuit 6. It may be formed inside the semiconductor integrated circuit 4 or outside the semiconductor integrated circuit 4. In this case, the oscillator circuit 6, the frequency divider circuit 16, and the multiplexer 17 are integrated into the same semiconductor integrated circuit 4. 1 shows an example in which the frequency detection circuit 18 is formed outside the semiconductor integrated circuit 4. are.

[0025] FIG. 3 shows an example in which the sensor circuit 12 has two oscillator circuits 6. If the frequency detection circuit 18 can directly detect the oscillation frequency of the oscillation circuit 6, the frequency divider circuit 16 is unnecessary. The oscillation signal of each oscillation circuit 6, the frequency of which is to be read, is first divided by the frequency divider circuit 16. After being divided by a predetermined integer N, the signal is selected by the multiplexer 17. The frequency detection circuit 18 detects the rising edge of the oscillation signal. By counting for a certain period of time, the oscillation frequency of the oscillation circuit 6 is estimated.

[0026] (Configuration of oscillator circuit 6) The oscillator circuit 6 includes a resonator 13 and a differential circuit 19. The resonator 13 includes an inductor 14 and a The oscillator circuit 6 responds to the physical properties (dielectric constant) of the liquid being inspected. The resonator 13 changes the oscillation frequency depending on the temperature and functions as a sensor that detects the physical properties of the liquid. is an LC circuit formed between the differential inputs of the differential circuit 19. The differential circuit 19 may be, for example, A known differential circuit, such as a differential circuit made up of cross-coupled transistors, is used. You may use it as you wish.

[0027] (Semiconductor integrated circuit 4 and test object 8) FIG. 4 shows the positional relationship between the semiconductor integrated circuit 4 provided in the bacteria testing device 1 and the test object 8. The semiconductor integrated circuit 4 includes a semiconductor substrate 21 and a The wiring layer 22 includes a wiring layer 22 formed on the wiring layer 22 and a protective film 23 formed on the wiring layer 22. In this way, an inductor 14 included in a resonator 13 of the oscillation circuit 6 is arranged. The inductor 14 of the resonant circuit 6 and the liquid that is the object under test 8 are insulated by a protective film 23. In order to detect changes in the dielectric constant of the test object 8 with good sensitivity, it is desirable that the protective film 23 be thin.

[0028] (Testing method for bacteria testing device 1) The bacteria testing device 1 configured in this manner tests the test subject 8 in the following manner. .

[0029] First, the oscillation of each effective oscillator circuit 6 was measured when a reference liquid containing no bacteria was poured into the well 5. The vibration frequency is then recorded. Next, the reference liquid is removed from the well 5, and the liquid of the test object 8 is poured into the well 5. Then, the oscillation frequency of each active oscillator circuit 6 is recorded, and a reference liquid is injected. Check the difference between the oscillation frequency when the It is determined that bacteria are present in the sensing area of ​​the oscillator circuit 6 that is larger than the sensing area of ​​the oscillator circuit 6 .

[0030] In another testing method, the liquid of the test object 8 is injected into the well 5, and each effective The oscillation frequency of each oscillator circuit 6 is recorded at regular intervals, and the change in the oscillation frequency of each active oscillator circuit 6 is recorded. In the oscillator circuit 6 where live bacteria are present in the sensing area, the oscillation frequency The change in the oscillation frequency of the oscillator circuit 6 that does not include live bacteria in the sensing area is larger than the change in the oscillation frequency of the oscillator circuit 6 that does not include live bacteria in the sensing area. This is because the structure of the water molecules around the live bacteria changes due to the activity of the live bacteria. It has been thought that the amount of change is greater than the amount of change determined in advance by experiments. The presence of an oscillator circuit 6 that exhibits a fast frequency change can be used to determine the presence of live bacteria.

[0031] In addition, the number N of oscillator circuits 6 in which the presence of live bacteria was confirmed on and the number of all oscillator circuits 6 used in the test N total The bacterial concentration in the test sample 8 is Bacteria concentration=N ON / (sensing area volume × N total ), It can be estimated that:

[0032] Considering this result, the test object 8 is 10 5 If the bacterial concentration is close to CFU / ml ( CFU stands for Colony Forming Unit, and indicates the presence of bacteria in the sensing area of ​​each oscillator circuit 6. The probability is low, and even if it does exist, it is usually only one bacterium. Upon checking, the results are as follows:

[0033] As shown in Non-Patent Document 1, the sensing area to be detected by one oscillator circuit 6 is The dimensions corresponding to the volume of the region are at most 100 μm×100 μm in the direction horizontal to the surface of the oscillation circuit 6. 100 μm in the direction perpendicular to the surface of the oscillator circuit 6, and 30 μm in the direction perpendicular to the surface of the oscillator circuit 6. 5 The average number of CFUs in the sample of test subject 8 is Sensing area volume / 10 5 CFU / ml =(100μm×100μm×30μm)×(10 5 / 10mm×10mm×10mm) =0.03 is.

[0034] That is, in the sensing area that one oscillator circuit 6 is to inspect, there are an average of 0.03 The probability distribution of the number of bacteria present in the sensing area follows a Poisson distribution. Therefore, for the test object 8 with such a low concentration, each oscillation circuit 6 determines the presence or absence of bacteria as 1 / 0 ( If the presence or absence is determined, the bacterial concentration of the test object 8 can be quantified from the ratio of the number of (present) cases. This is because the probability that the number of bacteria present in the sensing area is two or more is extremely low. be.

[0035] Furthermore, from a statistical perspective, the first embodiment can be understood as follows. The average number of CFU in a sample is 0.03, which means that in many cases, the sensing This means that the test volume in the region does not contain any bacteria. By arranging a plurality of oscillator circuits 6 each having a The distribution of the number of bacteria contained in the test sample volume is considered to be an average of 0.0 Since the probability of not containing bacteria in one test volume is given by P(0)=0.03×exp(-0.03) / 0!=0.97045, N oscillator circuits 6 each have a bacterial concentration of 10 5 CFU / ml of specimen volume was observed Then, the probability that one or more bacteria are contained in the sensing area of ​​at least one oscillator circuit 6 is 1-P(0) N , To make this probability 0.999 or more, 1-P(0) N ≧0.999, Therefore, if there are 231 or more oscillator circuits 6, the bacteria concentration will be 10 5 C If the test object 8 of FU / ml is observed, at least one oscillation circuit 6 will It is possible to observe changes in the temperature with a probability of over 99.9%.

[0036] (Effects of the First Embodiment) In the first embodiment, the oscillator circuits 6 are densely arranged to increase the sensing resolution. The number of oscillator circuits 6 can be increased without adding any difficult technical improvements to the sensor circuit 12. Furthermore, this method has the effect of improving the detection sensitivity. Only the presence or absence of bacteria needs to be judged as 0 / 1, and the total number of oscillator circuits 6 is positive. There is also an effect that the concentration of the test substance 8 can be quantified depending on the number of oscillation circuits 6 of the sexual reaction.

[0037] [Embodiment 2] Other embodiments of the present invention will be described below. For convenience of explanation, the above embodiment will be described. The same reference numerals are used to designate components having the same functions as those described above, and the description thereof will not be repeated. Don't repeat.

[0038] In rapid bacterial testing for specific bacteria, the number of target live bacteria in a sample or the concentration of target live bacteria is measured. Ronnie (target bacterial population) count is 10 per mL K pieces (10 K CFU / ml, CFU is Colon When the number of bacteria is 99.9% or more, the probability of determining that the target bacteria is present is 99.9%. If it is more than 10%, K CFU / ml is referred to as the detection limit concentration of the bacterial test.

[0039] The size of the sensing area to be detected by one oscillator circuit 6 is determined in the direction of the surface of the sensor circuit 12. The area is defined as X μm×Y μm in the direction perpendicular to the surface of the sensor circuit 12, and Z μm in the direction perpendicular to the surface of the sensor circuit 12. When the detection limit concentration of the specimen sample is in the detection area, the viable bacteria or viable The expected number of bacterial colonies is Sensing area volume / detection limit concentration =(X μm × Y μm × Z μm) × (10 K / 10 4 μm×10 4 μm×10 4 μm) =X Y Z 10 (K-12) is.

[0040] The distribution of the number of live bacteria or live bacterial colonies contained in the sensing area is expressed as the mean value X·Y· Z·10 (K-12) Since the Poisson distribution P(x) of When N oscillator circuits 6 having the same frequency are arranged, at least one oscillator circuit 6 is located in the sensing area. The probability that contains at least one live bacterium is 1-P(0) N =1-exp(-X Y Z 10 (K-12) ) N , Since this probability is greater than 0.999, 1-P(0) N ≧0.999, And by transforming the formula, N ≥ log(0.001) 10 (12-K) / (X Y Z) (Equation 1) This becomes:

[0041] A bacteria testing device in which N oscillator circuits 6 are arranged on the bottom surface of a well 5 holding a test object 8 is The detection limit concentration is 10 K CFU / ml can be achieved.

[0042] [Embodiment 3] FIG. 5 is a perspective view showing a schematic configuration of a bacteria testing device 1A according to the third embodiment. For convenience of explanation, the members having the same functions as those described in the above embodiment will be referred to as the same. Symbols are added and their explanations will not be repeated.

[0043] The bacteria testing device 1A includes a printed wiring board 20. Four semiconductor integrated circuits 4 arranged in two rows and two columns and a frequency detection circuit 18 are mounted on the do.

[0044] The four semiconductor integrated circuits 4 are each cut to expose a circular portion on the surface thereof. Wells 5 are formed on each semiconductor integrated circuit 4. The four wells 5 are, for example, P It is integrally composed of DMS.

[0045] In this way, four semiconductor integrated circuits 4 are mounted on the same printed wiring board 20, and each semiconductor A well 5 for holding a liquid to be inspected is formed on the conductor integrated circuit 4. This makes it possible to inspect multiple inspection targets simultaneously, leading to improved inspection efficiency.

[0046] The number of semiconductor integrated circuits 4 is not limited to four, as long as it is plural.

[0047] (Testing method for bacteria testing device 1A) First, a liquid containing no bacteria is placed in one of the four wells 5 as a reference. The liquid to be tested is placed in the well 5. Then, each effective oscillation of the well 5 containing the liquid to be tested is The frequency fluctuation of the circuit 6 is made to coincide with the frequency fluctuation of the oscillator circuit 6 of the well 5 containing the reference liquid. Next, the difference between the frequency fluctuation of the oscillator circuit 6 observing the reference liquid is The oscillation circuit 6 is connected to a liquid to be inspected containing live bacteria, the difference of which is larger than the difference determined in advance by an experiment. is determined to be observed.

[0048] The bacteria testing device 1A according to this embodiment is also a device for testing the drug susceptibility of bacteria to antibacterial drugs. First, one well 5 is filled with live bacteria. The liquid to be tested is poured into the wells 5, and the other three wells 5 contain test samples in which the presence of live bacteria has been confirmed. The elephant's liquid was injected with a solution containing three types of antibiotics that were the subject of drug susceptibility testing. Then, the time variation of the oscillation frequency of each of the effective oscillation circuits 6 of the four wells 5 is recorded. The oscillator circuit 6 placed at the bottom of one of the wells 5 to which no antibacterial agent was added was It is confirmed that there is an oscillator circuit 6 that exhibits a frequency change greater than a predetermined threshold (generation (Confirmation of the presence of bacteria).

[0049] Next, the other three wells 5 were recorded in parallel with the oscillator circuits 6 placed at the bottom of the wells. If there is no oscillator circuit 6 that exhibits a frequency change greater than a predetermined threshold, It is judged that the antibiotics added effectively acted on the live bacteria in the liquid and weakened their activity. can be done.

[0050] In addition, the oscillator circuits 6 arranged at the bottoms of the other three wells 5 are provided with a predetermined threshold. If there is an oscillator circuit 6 that exhibits a frequency change greater than It can be determined that the antibacterial effect against live bacteria in the liquid is weak.

[0051] [Embodiment 4] FIG. 6 is a perspective view showing the schematic configuration of a bacterial testing system 3 according to the fourth embodiment. For the sake of clarity, the same reference numerals will be used to designate components having the same functions as those described in the above embodiment. The number is added and the explanation is not repeated.

[0052] The bacterial testing system 3 includes a bacterial testing device 1A and a The housing 2 has a space including the bacteria testing device 1A held therein. The temperature controller 10 controls the temperature of the

[0053] The dielectric constant of a liquid changes significantly depending on its temperature. In order to measure the temperature of the liquid containing the bacteria, it is desirable to keep the temperature constant. The bacterial testing system 3 uses a housing 2 in which the bacterial testing device 1A can be fixed. This housing 2 can fix one or more bacteria testing devices 1A inside, and A temperature control device that controls the temperature of the space including the fixed bacteria testing device 1A so that the temperature is constant. The temperature control includes a control device 10. The temperature control includes controlling a heater, a cooler, etc. by measuring the temperature. A general method can be used.

[0054] The housing 2 has a control circuit 11 that controls the bacteria testing device 1A. When the device 1A is fixed, the bacteria testing device 1A is electrically connected to the control circuit 11. In this case, the control circuit 11 controls the bacteria testing device 1A to The necessary power can be supplied from the housing 2 side. The electrical control of the device 1A, detection of the oscillation frequency, and recording are performed by the control circuit 11 on the housing 2 side. is also possible.

[0055] By using the housing 2 configured in this manner, live bacteria testing using the bacteria testing device 1A can be performed. This makes it possible to carry out this process stably and efficiently.

[0056] In addition, in order to prevent cross-contamination in live bacteria testing, It is desirable to dispose of 1A after each live bacteria test. In this case, However, circuits that do not need to be built into the semiconductor integrated circuit 4 may be provided on the housing 2 side. This makes it possible to reduce the cost of the disposable bacteria testing device 1A.

[0057] FIG. 7 is a perspective view showing the schematic configuration of another bacterial testing system 3A according to the fourth embodiment. For convenience of explanation, the same reference numerals are used to designate components having the same functions as those described above. , and will not repeat the explanation.

[0058] The bacterial testing system 3A includes a plurality of bacterial testing devices 1A and a plurality of bacterial testing devices 1B. The inspection device is provided with a housing 2 that holds the vises 1A inside. This allows inspection of multiple inspection objects to be performed simultaneously. It can be done quickly and on time.

[0059] 〔summary〕 A bacterial testing device 1 / 1A according to the first aspect of the present invention comprises a semiconductor integrated circuit 4 and A test object is formed on the semiconductor integrated circuit 4 so as to expose a part of the surface of the integrated circuit 4. A well 5 for holding a liquid (subject 8) to be inspected, and the semiconductor integrated circuit in the well 5 A plurality of electrodes are arranged in the path 4, and the oscillation frequency of the electrodes changes depending on the change in the dielectric constant of the liquid (subject 8). a plurality of oscillator circuits 6, each of which is provided with a dielectric constant variable A sensing region capable of detecting the change is present in the liquid (subject 8), and the sensing region The area has a dimension of X μm and a dimension of Y μm in directions intersecting each other along the surface of the semiconductor integrated circuit 4. μm and a dimension Z μm in a direction intersecting the surface of the semiconductor integrated circuit 4, The number of paths 6 is N, and N is N≧log(0.001)·10 7 / (X Y Z ), satisfy.

[0060] According to this feature, the sensing regions intersect with each other along the surface of the semiconductor integrated circuit. Dimensions X μm and Y μm in the direction and dimension Z μm in the direction intersecting the surface of the semiconductor integrated circuit 4 m, and the number of oscillator circuits is N, where N≧log(0.001) 10 7 / (X Y Z ), the number of target live bacteria in the sample is 10 per mL. 5 When there are more than one, The probability of determining that the target bacteria is present is 99.9% or more. There is a probability that at least one oscillator circuit will detect the bacteria. This eliminates the need to wait until the change in dielectric constant is detected, and even when the bacterial concentration is low, It is possible to detect the change.

[0061] The bacteria testing device 1 / 1A according to the second aspect of the present invention comprises a semiconductor integrated circuit 4 and A test object is formed on the semiconductor integrated circuit 4 so as to expose a part of the surface of the integrated circuit 4. A well 5 for holding a liquid (subject 8) to be inspected, and the semiconductor integrated circuit in the well 5 A plurality of electrodes are arranged in the path 4, and the oscillation frequency of the electrodes changes depending on the change in the dielectric constant of the liquid (subject 8). a plurality of oscillator circuits 6, each of which is provided with a dielectric constant variable A sensing region capable of detecting the change is present in the liquid (subject 8), and the sensing region The regions have a dimension X=100 μm in a direction intersecting each other along the surface of the semiconductor integrated circuit 4 and and a dimension Y=100 μm, and a dimension Z=30 μm in a direction intersecting the surface of the semiconductor integrated circuit 4. m, and the concentration of the test target bacteria is 10 5 CFU / ml of the half-life in each well 5 The number of the oscillator circuits 6 arranged in the semiconductor integrated circuit 4 is 231 or more.

[0062] According to this feature, the sensing regions intersect with each other along the surface of the semiconductor integrated circuit. The dimension X=100 μm and the dimension Y=100 μm in the direction intersect with the surface of the semiconductor integrated circuit. The dimension in the direction Z=30 μm, and the concentration of bacteria to be inspected is 10 5 CFU / ml, and The number of oscillator circuits arranged in the semiconductor integrated circuit in the well is 231 or more. At least one oscillator circuit is capable of detecting changes in dielectric constant due to bacteria with a probability of 99.9% or more. As a result, there is no need to wait until the bacteria grow before detecting the change in dielectric constant. Therefore, the change in the dielectric constant can be detected even when the bacterial concentration is low.

[0063] A bacteria testing device 1A according to a third aspect of the present invention is the device according to the second aspect, further comprising: A plurality of circuits 4 are provided, and the well 5 is formed on each semiconductor integrated circuit 4, The number of the oscillator circuits 6 arranged in the semiconductor integrated circuits 4 in the well 5 is 231 or more. It is preferable that:

[0064] According to the above configuration, it is possible to simultaneously and quickly perform inspections on a plurality of inspection targets. .

[0065] The bacterial testing system 3 / 3A according to the fourth aspect of the present invention is a bacterial testing system according to the first or second aspect of the present invention. A test device 1·1A and a housing 2·2A that holds the bacteria test device 1·1A therein. The housing 2 / 2A includes the bacteria testing device 1 / 1A held therein. The apparatus has a temperature controller 10 for controlling the temperature of the space containing the apparatus.

[0066] According to the above configuration, the dielectric constant of a liquid, which varies greatly with temperature, can be measured at a constant temperature. It is possible.

[0067] The bacterial testing system 3 / 3A according to the fifth aspect of the present invention is the bacterial testing system 3 / 3A according to the fourth aspect, further comprising: It is preferable that the bacteria testing device 1·1A has a control circuit 11 for controlling the bacteria testing device 1·1A. stomach.

[0068] According to the above configuration, it is possible to supply the power required for the bacteria testing device from the housing side. It also controls the electrical properties of the bacteria testing device fixed inside, and detects and records the oscillation frequency. This can also be done on the housing side.

[0069] A bacterial testing system 3A according to a sixth aspect of the present invention is the bacterial testing system 3A according to the fourth or fifth aspect, further comprising: It is preferable that 2A holds a plurality of bacteria testing devices 1A inside.

[0070] According to the above configuration, it is possible to simultaneously and quickly inspect a large number of inspection targets. .

[0071] The present invention is not limited to the above-described embodiments, and various modifications within the scope of the claims are possible. Modifications are possible, and the technical means disclosed in the different embodiments may be appropriately combined. The resulting embodiments are also within the scope of the present invention. [Explanation of symbols]

[0072] 1. Bacteria testing device 2. Case 3 Bacteriological testing system 4. Semiconductor Integrated Circuits 5 wells 6 Oscillator Circuit 8 Test object (liquid) 10 Temperature Controller 11 Control circuit 12 Sensor Circuit 13 Resonator 14 Inductors 15 Capacitor 16 frequency divider circuit 17 Multiplexer 18 Frequency detection circuit 19 Differential Circuit 20 Printed wiring board 21 Semiconductor substrate 22 wiring layer 23 Protective film

Claims

1. A plurality of semiconductor integrated circuits; a plurality of wells formed on each of the plurality of semiconductor integrated circuits so as to expose a portion of a surface of each of the plurality of semiconductor integrated circuits, the wells holding a liquid to be inspected; a plurality of oscillation circuits disposed in the semiconductor integrated circuits in the plurality of wells, the oscillation frequency of which changes in response to a change in the dielectric constant of the liquid; a sensing region capable of detecting a change in the dielectric constant due to the presence of bacteria is present in the liquid, the sensing region corresponding to each of the plurality of oscillation circuits; A liquid containing no bacteria is placed in a first well of the plurality of wells; pouring a liquid to be tested into a second well different from the first well among the plurality of wells; A bacteria testing device characterized in that if the difference in output between the oscillator circuits corresponding to the first and second wells is greater than a predetermined value, it is determined that the liquid in the second well contains bacteria.

2. A plurality of semiconductor integrated circuits; a plurality of wells formed on each of the plurality of semiconductor integrated circuits so as to expose a portion of a surface of each of the plurality of semiconductor integrated circuits, the wells holding a liquid to be inspected; a plurality of oscillation circuits disposed in the semiconductor integrated circuits in the plurality of wells, the oscillation frequency of which changes in response to a change in the dielectric constant of the liquid; a sensing region capable of detecting a change in the dielectric constant due to the presence of bacteria is present in the liquid, the sensing region corresponding to each of the plurality of oscillation circuits; A liquid containing bacteria is placed in a first well and a second well of the plurality of wells; adding an antibacterial agent to be measured to the second well of the plurality of wells; The outputs of the oscillator circuits corresponding to the first and second wells are compared, and a change in the output of the oscillator circuit of the second well is smaller than a change in the output of the oscillator circuit of the first well. A bacteria testing device characterized by evaluating whether the antibacterial effect of the antibacterial drug is present.

3. A bacterial testing device according to claim 1, a housing that holds the bacteria testing device therein; a frequency detection circuit provided inside the housing for detecting an output of the oscillator circuit from the bacteria testing device.

4. A bacterial testing device according to claim 2, a housing that holds the bacteria testing device therein; a frequency detection circuit provided inside the housing for detecting an output of the oscillator circuit from the bacteria testing device.

5. The number N of the oscillator circuits arranged in the semiconductor integrated circuit in each well is 231 or more, When the volume of the sensing region is V (mm 3 ), 1-exp(-N×V×100)≧0.999…(condition 1), 3. The bacteria testing device according to claim 1, wherein the above-mentioned condition is satisfied.

6. A bacterial testing system as described in claim 3 or 4, characterized in that the housing has a temperature controller that controls the temperature of the space containing the bacterial testing device held therein.

7. A bacterial testing system as described in claim 3 or 4, characterized in that the bacterial testing device is disposable after each test.

8. An inspection method using a bacteria inspection device comprising: a plurality of semiconductor integrated circuits; a plurality of wells formed on each of the plurality of semiconductor integrated circuits so as to expose a portion of the surface of each of the plurality of semiconductor integrated circuits and holding a liquid to be inspected; and a plurality of oscillation circuits disposed on each of the semiconductor integrated circuits in the plurality of wells and whose oscillation frequency changes with a change in the dielectric constant of the liquid, wherein a plurality of sensing regions capable of detecting the change in dielectric constant due to the presence of bacteria are present in the liquid corresponding to each of the plurality of oscillation circuits, Placing a bacteria-free liquid in a first sensing area among the plurality of sensing areas; placing a liquid to be tested in a second sensing area different from the first sensing area among the plurality of sensing areas; and if the difference in output between the oscillator circuits corresponding to the first and second sensing areas is greater than a predetermined value, determining that the liquid to be tested placed in the second sensing area contains bacteria.

9. An inspection method using a bacteria inspection device comprising: a plurality of semiconductor integrated circuits; a plurality of wells formed on each of the plurality of semiconductor integrated circuits so as to expose a portion of the surface of each of the plurality of semiconductor integrated circuits and holding a liquid to be inspected; and a plurality of oscillation circuits disposed on each of the semiconductor integrated circuits in the plurality of wells and whose oscillation frequency changes with a change in the dielectric constant of the liquid, wherein a plurality of sensing regions capable of detecting the change in dielectric constant due to the presence of bacteria are present in the liquid corresponding to each of the plurality of oscillation circuits, placing a liquid containing bacteria in a first sensing area and a second sensing area among the plurality of sensing areas; adding an antibacterial agent to be measured to the second sensing region among the plurality of sensing regions; a step of comparing the outputs of the oscillator circuits corresponding to the first and second sensing areas, and evaluating that the antibacterial agent has an antibacterial effect if the change in the output of the oscillator circuit of the second sensing area is smaller than the change in the output of the oscillator circuit of the first sensing area.

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