WO2017134804A1 - Sensor element and sensor device - Google Patents

Sensor element and sensor device Download PDF

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Publication number
WO2017134804A1
WO2017134804A1 PCT/JP2016/053435 JP2016053435W WO2017134804A1 WO 2017134804 A1 WO2017134804 A1 WO 2017134804A1 JP 2016053435 W JP2016053435 W JP 2016053435W WO 2017134804 A1 WO2017134804 A1 WO 2017134804A1
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Prior art keywords
chamber
sensor element
fet
insulating layer
sensor
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PCT/JP2016/053435
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French (fr)
Japanese (ja)
Inventor
田井　光春
健三 黒土
真斗 永田
聖一 鈴木
高橋　宏昌
典史 亀代
安藤　正彦
希倫 何
雄二 諏訪
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株式会社日立製作所
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Priority to PCT/JP2016/053435 priority Critical patent/WO2017134804A1/en
Publication of WO2017134804A1 publication Critical patent/WO2017134804A1/en

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
    • G01N27/403—Cells and electrode assemblies
    • G01N27/414—Ion-sensitive or chemical field-effect transistors, i.e. ISFETS or CHEMFETS

Definitions

  • the present invention relates to a sensor element and a sensor device, and more particularly to a sensor element and a sensor device to which a bio-FET (field effect transistor) capable of achieving high sensitivity and long life is applied.
  • a bio-FET field effect transistor
  • Bio-FET Field-Effect-Transistor
  • the Bio-FET has a structure in which a potential induced by a detection target can be applied to the gate electrode of the transistor. Since the target detection signal is amplified in an analog manner according to the signal intensity by the transistor, it is a suitable device as a sensor element for molecular detection.
  • Bio-FET has been proposed with a plurality of methods depending on a method of generating an induced potential.
  • the latter method does not cause problems in the former method, but there is no general method for designing (searching) or loading antibodies that promote the redox action of the molecules to be detected, and for the presence or absence of a solution for each detection target. Therefore, the subject is limited.
  • a biological cell membrane or artificial lipid bilayer membrane composed of a lipid bilayer carrying a receptor whose ligand is the molecule to be detected is sandwiched between electrolytes, and the target molecule is captured by the receptor.
  • an FET that applies a potential induced to a gate electrode.
  • Biological cell membranes induce membrane potentials on the order of tens of millivolts for detection targets as small as ppm, ppb, and ppt. This is a potential detectable by a transistor, and a highly sensitive molecular sensor device can be realized.
  • the potential induced in this way is the difference in ion concentration between the two electrolytes on both sides of the lipid bilayer, resulting from the movement of ions in the electrolyte in a certain direction through the ion channel where the target molecule is captured and expressed by the receptor. Derived from. Therefore, the structural fluctuation of the target molecule and the problem of electrolyte screening do not occur. Further, in principle, the molecules to be detected and the detection sensitivity can be realized for those that can be realized in a living body.
  • the problem with FETs composed of lipid bilayers is the stable film formation of the lipid bilayer on top of the FET and the lifetime after film formation.
  • a method of forming holes in a hydrophobic resin substrate and forming a lipid bilayer in the hole portion has been the mainstream.
  • the FET and the lipid bilayer are made on different substrates, and then the substrates are bonded together.
  • the size of the device increases due to the need to ensure the yield of the bonding process.
  • the yield of the bonding process multiplied by the yield of the finished product, the device yield decreases.
  • the FET is generally formed on a substrate having a coefficient of thermal expansion that is significantly different from that of a resin substrate such as a silicon substrate, the reliability of the device is also lowered.
  • the present invention provides a sensor element including a field effect transistor (FET) formed on an insulating substrate, a first chamber formed above a channel included in the FET, A second chamber formed above the first chamber, wherein the first chamber and the second chamber are filled with an electrolyte solution, and the first chamber and the second chamber A configuration in which a lipid bilayer is formed at the boundary is adopted.
  • FET field effect transistor
  • the device size can be reduced.
  • the number of parts and the number of processes can be reduced, and the cost can be reduced.
  • FIG. 5 is a plan view below the upper chamber of the device of FIG. 4. It is sectional drawing corresponding to the cross section X1 of FIG. It is sectional drawing corresponding to the cross section X2 of FIG. FIG. 5 is a cross-sectional view corresponding to a cross section Y in FIG. 4. It is sectional drawing which shows the other structure of the device in this embodiment. It is sectional drawing which shows the other structure of the device in this embodiment.
  • FIG. 1 is a cross-sectional view of an FET in this embodiment.
  • a source 2 and a drain 3 formed of a high-concentration impurity layer and an FET channel layer 4 sandwiched between these regions are formed on a silicon substrate 1, and a gate insulating layer 5 and a micro chamber 6 are defined above the source 2 and drain 3.
  • An insulating layer 7 is formed.
  • the insulating layer 7 is formed with holes or grooves to define the minute chamber 6.
  • An artificial or living body lipid bilayer membrane 8 is formed on the upper surface of the hole or groove defining the micro chamber 6 so as to cover the hole or groove, and the micro chamber 6 and the upper chamber 9 are separated.
  • the upper chamber 9 is defined by a sheath 10 made of an insulating layer provided separately. If the sheath 10 can be formed from the same material as the insulating layer that defines the gate insulating layer 5 and the micro chamber 6, it is efficient in terms of manufacturing process, but the upper chamber 9 can be shared by a plurality of FETs. Therefore, even if the size of the device is reduced, the likelihood of pasting can be ensured. Therefore, for example, a method of forming with an organic resin such as acrylic and bonding in a later step may be used.
  • the microchamber 6 and the upper chamber 9 are filled with an electrolyte solution to reproduce the environment inside the living cells (corresponding to the microchamber 6) and extracellular (corresponding to the upper chamber 9).
  • a reference electrode 11 is formed in the upper chamber 9 to stabilize the operation of the FET.
  • at least two micro-channels 12 are formed in the sheath 10 that defines the upper chamber 9 for waste and filling of the electrolyte solution.
  • a receptor 13 that acts as an ion channel for a specific molecule is embedded in the lipid bilayer membrane 8 that separates the micro chamber 6 and the upper chamber 9.
  • the ion channel is opened accordingly, and a specific ion in the electrolyte is transported in one direction.
  • a difference in ion concentration occurs between the micro chamber 6 and the upper chamber 9, and a potential difference is generated above and below the lipid bilayer membrane 8.
  • the sum of the potential of the reference electrode 11 and the potential difference is applied to the upper portion of the gate insulating layer 5 of the FET.
  • This potential difference is usually on the order of several tens of mV, and can be sufficiently detected by a conventional FET. Since the minute chamber 6 is formed so as to cover the upper part of the FET channel 4, the potential difference is applied to the entire region of the FET channel 4 to form an inversion layer serving as a current path.
  • the size of the device is several in order to secure the likelihood of bonding between the substrate containing the chamber filled with the electrolyte solution and the substrate on which the active layer (consisting of the source, drain, and channel of the FET) is formed. It was technically difficult to form with a thickness of 10 ⁇ m or less.
  • the device configuration of this embodiment at least the microchamber below the cell membrane can be formed on the same substrate as the active layer of the FET and with the same scale accuracy. Therefore, the device size can be reduced. In addition, the number of parts and the number of processes can be reduced, and the cost can be reduced.
  • the film thickness of the gate insulating layer 5 can be reduced with the accuracy of the FET manufacturing process. By making the gate insulating layer 5 thinner, it is possible to improve the amplification factor of the FET and reduce the signal noise, thereby realizing a sensor device with high detection sensitivity.
  • the volume of the micro chamber 6 can be miniaturized within the accuracy range possible in the FET manufacturing process. For example, typically, a hole or groove having a diameter or width of 500 to several thousand nm and a depth of about several thousand nm can be formed, but it may be designed according to the application and required detection accuracy.
  • the concentration fluctuation amount of the micro chamber 6 with respect to the amount of ions exchanged between the micro chamber 6 and the upper chamber 9 increases, and the time until concentration equilibrium is shortened. As a result, the time during which the potential difference occurs is also shortened. Therefore, a sensor device having a quick time response can be realized.
  • FIG. 2 is a plan view of the device below the microchamber 6 in FIG.
  • a perspective view of the FET source 2, drain 3, and FET channel 4 is shown.
  • the hole or groove region defining the micro chamber 6 shown in FIG. 1 is formed so as to cover the upper part of the FET channel 4, and the film thickness of the insulating layer 7 on the FET channel 4 is a hole or groove. It is designed to be thinner than the part where no is formed. That is, the film thickness of the gate insulating layer 7 of the FET is defined by the depth of the hole or groove.
  • FIG. 3 is a plan view of the device below the upper chamber 9.
  • the lipid bilayer membrane 8 that partitions the upper chamber 9 and the micro chamber 6 is omitted.
  • the sheath 10 that defines the upper chamber 9 has at least two microchannels 12 formed therein. 1 and 3, the sheath 10 covers the upper part of the microchannel 12. However, after the channel is formed in a groove shape, the microchannel 12 may be covered with another material. An electrolyte solution, a lipid solution, a surfactant, and the like are appropriately exchanged and supplied to one side of the microchannel 12. Each solution is discarded from the other side.
  • the lipid bilayer membrane can be dissolved, discarded, and reformed, and the effective life of the device can be increased.
  • FIG. 4 is a plan view below the microchamber having a configuration different from that of the device shown in FIG.
  • FIG. 5 is a plan view of the device below the upper chamber 9 of the device shown in FIG. In FIG. 5, as in FIG. 3, the lipid bilayer membrane 8 that partitions the upper chamber 9 and the micro chamber 6 is omitted.
  • a plurality of grooves defining the micro chamber 6 are provided in the direction in which the current of the FET flows, that is, in the direction parallel to the lines of the cross section X1 and the cross section X2. Further, each groove covers at least a part of each region of the source 2 and the drain 3 and a part of the FET channel 4.
  • the groove-like microchamber 6 has a smaller opening surface, so that the surface tension applied to the lipid bilayer membrane 8 formed on the upper end surface can be relaxed. Therefore, a stable device is realized.
  • two microchannels 12 are installed on the wall surface of the two sheaths 10 facing the two short sides of the groove.
  • the lipid solution flows in parallel to the short side of the groove defining the microchamber, and the membrane surface is also formed along the tip surface into which the lipid solution flows. . Since the repulsive force due to surface tension applied to the membrane during membrane surface formation is smaller when it is pulled on the short side than on the long side, this structure makes it possible to form a lipid bilayer membrane more stably. It becomes.
  • FIG. 6 is a cross-sectional view corresponding to the cross section X1 in FIGS. 4 and 5
  • FIG. 7 is a cross-sectional view corresponding to the cross section X2 in FIGS. 4 and 5
  • FIG. 8 corresponds to the cross section Y in FIGS. FIG. 6 and 7, the FET channel 4 is not shown.
  • the FET channel 4 serving as a current path is formed only in the region of the FET channel 4 where the micro chamber 6 exists in the upper part.
  • the reference electrode 11 is formed so as to cover the upper surface of the upper chamber 9, and includes an opening 14 opened in a groove shape.
  • the opening 14 is formed in the upper part of the micro chamber 6. That is, the opening 14 is processed so as to have a projection relationship with respect to the silicon substrate 1.
  • the opening 14 is connected to the external environment, and molecules to be detected are dissolved in the electrolyte solution in the upper chamber 9 through the opening 14. As described above, the target molecule needs to be transported to the receptor 13 for detection.
  • the reference electrode 12 is formed so as to cover the upper chamber 9 except for the opening 14, so that the positional relationship such as the distance with respect to each micro chamber 6 approaches uniformly.
  • the layout has the shortest distance that the target molecule moves from the opening 14 to the receptor 13, it is possible to provide a uniform and quick response device.
  • the bulk FET (shown in FIGS. 6 and 8) created on the silicon substrate 1 is shown as an example.
  • the FET created on the SOI substrate 60 as shown in FIG. High performance FET can be provided.
  • the SOI substrate 60 formed on the silicon substrate 1 is applied to the active layer. As a result, the stray capacitance between the parasitic diode and the silicon substrate can be suppressed, and the high-speed response of the device and the leakage current can be suppressed.
  • FIG. 9 shows an application example to the device shown in FIGS. 1 to 3, but it can also be applied to the device shown in FIGS. 4 to 8.
  • FIG. 10 is a cross-sectional view of a device having a configuration different from that shown in FIGS.
  • at least two or more FETs are formed in the lower part of the upper chamber 9, and the minute chambers 6 are formed in the upper parts of the FETs, and the volumes of the minute chambers 6 are different from each other. .
  • one of the effects of providing the micro chamber 6 is that the target molecule is captured by the receptor 13 and the time response of the concentration fluctuation in the electrolyte solution due to the opening of the specific ion channel is accelerated. If the volume of the chamber 6 is different, the response speed is also different. Qualitatively, when the concentration of the target molecule is small, the response is good with an FET with a small volume of the micro chamber 6, and the response is insensitive with an FET with a large volume of the micro chamber. On the other hand, when the concentration of the target molecule is large, the response is saturated in the FET with the small volume of the micro chamber 6, and the response is good with the FET with the large volume of the micro chamber 6.
  • the device is configured by at least two or more FETs having different volumes of the micro chamber 6.
  • the volume of the micro chamber 6 can be freely set within the range of the FET manufacturing process. Therefore, it is possible to provide a molecular detection device having a wide detectable concentration range.
  • the same channel pair as the microchannel pair used for lipid bilayer membrane reconstruction or another microchannel pair is provided to circulate the electrolyte solution in the upper chamber. Functions can be added.
  • FIG. 11 is a cross-sectional view of the device when the FET shown in FIG. 1 is applied.
  • the configuration of FIG. 11 can be applied to all the FETs shown in FIGS.
  • a selection valve is provided upstream on the inflow side and downstream on the outflow side.
  • the flow path may be branched.
  • the electrolyte solution circulates between the upper chamber 9 and the intake chamber 21 by the electrolyte circulation device 20.
  • the electrolyte circulation device 20 may employ a micropump employed in the ⁇ -TAS technology or the like, MEMS, or the like.
  • the design position and design area of the intake chamber 21 can be freely designed independently of the positions and sizes of the FET, the micro chamber, and the upper chamber.
  • the area of the intake port 22 can be enlarged and an efficient shape layout can be realized, and a device with extremely high detection sensitivity can be realized.
  • FIG. 12 is a diagram for explaining the procedure for reconstitution of the lipid bilayer membrane.
  • the electrolyte solution 23 filling the micro chamber 6 is introduced into the empty device (FIG. 12 (a)) through the microchannel 12 (FIG. 12 (b)). Subsequently, a lipidic solution 24 containing a lipid constituting the lipid bilayer membrane and a receptor protein is introduced into the upper chamber 9 through the microchannel 12 (FIG. 12 (c)). At this time, the electrolyte solution 23 remains inside the micro chamber 6, and a lipid single membrane 25 is formed between the electrolyte solution 23 and the lipidic solution 24.
  • the lipid single membrane 25 is arranged with the hydrophilic group facing the electrolyte solution 23 and the hydrophobic group facing the lipidic solution 24.
  • the boundary between the electrolyte solution 23 and the lipidic solution 24, that is, the position where the lipidic single membrane 25 is formed is stable along the opening surface starting from the edge of the microchamber opening surface because the interfacial energy of the system is minimized. (FIG. 12C).
  • the electrolyte solution 26 that fills the upper chamber 9 is filled through the micro flow path 12.
  • the second-layer lipid molecules are arranged so as to cover the hydrophobic group of the lipidic single membrane 25, and the lipid bilayer membrane 8 is formed (FIG. 12 (d)).
  • a protein such as a receptor molecule embedded in the lipid bilayer membrane 8 is between the timing at which the lipid monolayer 25 is formed and the timing at which the lipid bilayer 8 is formed according to the stability of the molecular structure and interfacial energy. Is taken in from time to time. As described above, there is a method of positively embedding receptor molecules using a surfactant or thermal vibration, in addition to utilizing a phenomenon in which receptor molecules are naturally embedded.
  • a surfactant is introduced through the microchannel 12. Thereby, lipid molecules constituting the lipid bilayer membrane 8 are eluted in the electrolyte solution. Thereafter, the electrolyte solution 23 to be filled in the micro chamber 6 is introduced, and the lipid molecules are removed by draining the already filled solution through the other microchannel 12.
  • thermal vibration may be applied in order to accelerate the elution of lipid molecules.
  • a hydrophilic insulating layer 27, a hydrophobic insulating layer 28, and a hydrophilic insulating layer 29 are stacked in this order from the silicon substrate 1 under the upper chamber 9.
  • the lipid bilayer membrane 8 can be formed more stably and reproducibly on the opening surface of the micro chamber 6.
  • FIG. 13B is an enlarged view of the end of the micro chamber 6.
  • the lipid bilayer membrane 8 is formed starting from the end of the microchamber 6.
  • the lipid hydrophobic group 31 is attracted to the hydrophobic insulating layer 28, and the lipid hydrophilic group 32 is attracted to the hydrophilic insulating layers 27 and 29, and becomes the starting point of the lipid bilayer membrane 8.
  • the lipid molecule 30 is a chain molecule, most of which has a length of several nm, as described above, it is desirable that the hydrophobic insulating layer 28 and the hydrophilic insulating layer 29 are laminated with a thickness of 1 to 2 nm.
  • the hydrophilic insulating material includes, for example, a silicon oxide film
  • the hydrophobic insulating material includes, for example, a silicon nitride film to which a chemical vapor deposition method using monosilane and nitrogen as raw materials is applied.
  • the structure shown in FIG. 13 can be realized by selecting the material, a thin film using the same constituent material can be realized by applying a general surface treatment to the laminated film or by controlling the raw material and film forming conditions of the laminated film.
  • the hydrophobicity and hydrophilicity of the membrane can be controlled relatively easily.
  • the film thickness can be controlled in units of several nanometers by controlling the film formation time in, for example, chemical vapor deposition or physical vapor deposition, and is not particularly difficult in a general FET formation process.
  • the method for forming the device structure of the present embodiment will be described with reference to a process example for forming the device example shown in FIG.
  • the details of the FET forming process are based on a well-known MOS forming process and are well-known techniques.
  • a well is formed on the surface of the silicon substrate 1 as necessary.
  • element isolation is performed using a LOCOS (Local Oxidation of Silicon) process or an STI (Shallow Trench Isolation) process.
  • LOCOS Local Oxidation of Silicon
  • STI Shallow Trench Isolation
  • the region excluding the source / drain regions is covered with a photoresist 34 (FIG. 14B).
  • impurities are introduced into the source / drain regions by ion implantation to form an impurity introduction layer 35.
  • the impurity to be introduced is an element such as phosphorus or arsenic.
  • the impurity to be introduced is an element such as boron or aluminum.
  • a thick insulating layer 7 is formed (FIG. 14C).
  • a chemical vapor deposition method is used to shorten the film formation time.
  • the film thickness is controlled in accordance with the size of the micro chamber, but a typical value is 1 ⁇ m to 10 ⁇ m.
  • the film quality (density, defect density, etc.) of the insulating layer 7 is dense, that is, high-quality and has a low defect density.
  • the film quality is sensitive to the switching characteristics of the FET, so that high quality is essential.
  • the film thickness is as thick as 1 ⁇ m to 10 ⁇ m, the film formation time becomes long. Therefore, it is not realistic to make the entire insulating layer 7 high in terms of cost and manufacturing time.
  • the insulating layer 7 may be formed as a film having a non-homogeneous film quality.
  • the lower layer part of the insulating layer 7 that functions as a gate insulating film is composed of a high-quality film with high density (dense) and small defect density, and the upper layer part of the insulating layer 7 has a higher deposition rate (than the lower layer part). (Also low density).
  • an oxide film having a short film formation time has poor film quality and is not suitable as a gate insulating layer of an FET. Therefore, it is desirable to form a thermal oxide film of about 10 nm for the gate insulating layer of the FET before forming the thick insulating layer.
  • a thermal oxide film of about 10 nm for the gate insulating layer of the FET before forming the thick insulating layer.
  • a silicon nitride film is additionally formed on the gate insulating layer formed of a thermal oxide film, for example, by several nm to several tens of nm, thereby further ensuring a high selection ratio.
  • the source / drain forming oxide film is removed, but when this oxide film is formed by thermal oxidation or the like and can be sufficiently applied as a gate insulating layer of an FET, this oxide film is not removed, A thick insulating layer may be formed thereon.
  • the micro chamber 6 is processed using a lithography process (FIG. 14D).
  • the processing shape is controlled by the photoresist 36. Regions not covered with the photoresist are processed by anisotropic dry etching to form holes or grooves. If necessary, a protective film with a higher selectivity may be formed and processed under the photoresist. Since the film quality and film thickness of the gate insulating layer are factors that determine the controllability and uniformity of the FET, it is extremely important to control them.
  • the film quality of the gate insulating layer, the micro chamber after the formation is improved.
  • the micro-channel 12, the reference electrode 11, the micro-pump, and the casing 37 in which the MEMS is incorporated are bonded to the substrate.
  • At least one and two microchannels 12 are formed on the housing side wall 38.
  • the reference electrode 11 is embedded in the housing lid portion 39 so that a voltage can be applied to the upper chamber side electrolyte solution 26 from the outside.
  • the material constituting the housing includes an oxide film having the same thickness as the microchamber and an organic insulating material such as acrylic. If the former material (an oxide film with the same thickness as that of the micro chamber) is used, it is possible to perform batch processing up to the side wall of the housing in the FET forming process, and it is freed from the problem of bonding accuracy. In this case, miniaturization including the upper chamber is possible, and a micro sensor module capable of detecting a plurality of types of detection objects can be provided. Moreover, even if the latter material (organic insulating material such as acrylic) is used and the upper chamber is formed in consideration of the bonding likelihood, the main effect that can be realized in this embodiment is very small. Since it is brought about by the presence of the chamber, the benefits obtained in this embodiment can be enjoyed.
  • an organic insulating material such as acrylic
  • FIG. 15A is a diagram in which the device of the upper chamber 9 is virtually opened to look down on the device. Eighteen micro-chambers 6 are opened corresponding to one large upper chamber, and FETs are formed in the respective lower portions.
  • FIG. 15 shows an example in which the reference electrode 11 is provided in the center of the casing lid portion 39, but it is also possible to provide the reference electrode 11 on the entire upper surface of the upper chamber 9 or in a mesh shape. By doing so, it is possible to provide a sensor array including a sensor group in which the electric field distribution is uniform in the sensor array region and the sensitivity distribution is small.
  • FIG. 16 is a functional block diagram of a sensor device to which the FET shown in FIG. 1, FIG. 6, FIG. 8 to FIG.
  • Supply unit 50 for supplying electrolyte solution A (electrolyte solution 23 in FIG. 12B) filling microchamber 6 to microchannel 12 formed in the FET or FET array, and electrolyte solution B (see FIG. 12) filling upper chamber 9 12 (b), a supply unit 51 for supplying the electrolyte solution 26), a supply unit 52 for supplying a lipid solution (lipidic solution 24 in FIG.
  • a supply unit 53 that supplies a surfactant solution that elutes the bilayer membrane, a waste liquid unit 54 that collects (regenerates) the waste liquid containing the eluted lipid bilayer membrane, the type and flow of the liquid to be supplied or discarded It consists of a valve group for controlling the path and a control unit 55 for controlling these parts.
  • a circulation part 56 for taking the molecules to be detected from the external environment into the electrolyte solution B and guiding them to the FET is added, but this is added as necessary.
  • the lipid bilayer membrane can be discarded or reconfigured in a timely manner, so that a long-life device with good deterioration resistance can be provided.
  • FIG. 17 is a timing chart showing the operation of the sensor device having the functional block diagram shown in FIG.
  • the vertical axis represents the function operation and the function stop by 1 value and 0 value, respectively, and the horizontal axis represents time, and represents the change over time.
  • the electrolyte solution A is filled into the micro chamber 6 and the upper chamber 9 through the micro flow path 12.
  • the valve of the waste liquid part 54 is closed, but filling may be performed while opening the waste liquid by deliberately opening. By doing so, the inside of the chamber can be purged and cleaned with the electrolyte solution A.
  • the lipid solution 24 is introduced. At this time, the electrolyte solution A filled in the microchamber 6 remains, and a lipid monolayer 25 is formed at the interface with the lipid solution 24.
  • the electrolyte solution B is introduced into the upper chamber 9.
  • the electrolyte solution B advances to the waste liquid system 54 side while extruding the lipid solution 24.
  • the lipid group constituting the lipid solution 24 and the hydrophobic group of the lipid single membrane 25 are formed.
  • the molecules are arranged so that the hydrophobic groups face each other, and a lipid bilayer is formed on the side opposite to the tangential movement direction.
  • the valves of the supply parts 50 to 53 and the waste liquid part 54 are closed, and the FET 49 and the circulation part 56 (when installed) are operated to perform molecular sensing.
  • the FET 49 and the circulation unit 56 are stopped, and all the valves of the circulation unit 56 are closed.
  • the valves of the supply unit 53 for supplying the surfactant solution and the waste liquid unit 54 are opened, and the electrolyte solutions A and B and the lipid bilayer membrane are eluted and discarded.
  • electrolyte solution A is introduced again, and the lipid bilayer membrane is reconfigured through the same sequence.
  • Electrochemical solution A and B chamber filling, residue, formation of lipid monolayers and bilayers, and disposal of lipid membranes are important in controlling the flow rate of the raw material solution and waste solution.
  • the flow rate of the solution is controlled by the control unit, for example, with an MFC (Mass Flow Controller) installed in the pipe.
  • MFC Mass Flow Controller
  • the opening and closing of the valve group is controlled by the control unit.
  • the sensor device having the configuration shown in FIG. 16 molecular sensing is not possible during the elution and disposal of the electrolyte solutions A and B, the lipid bilayer membrane, and the lipid bilayer membrane reconfiguration.
  • the sensor device having the configuration shown in FIG. 18 can provide a device that can always perform sensing.
  • the functional blocks of the supply unit, the disposal unit, and the control unit are the same as in FIG. 16, but two FET sensors with the same structure (A and B) and two types of selection valves (selection valves 1 and 2). Have been added.
  • the selection valve and switching the flow path the sensor device can always perform sensing by executing the sensing sequence of each FET and the lipid bilayer reconfiguration sequence at different timings. is there.
  • FIG. 19 is a timing chart showing the operation of the sensor device having the functional block diagram shown in FIG.
  • the FET to be operated is selected by switching the selection valve 1, and the FET for reconfiguring the lipid bilayer membrane is selected by switching the selection valve 2.
  • the selection valves 1 and 2 select micro-channels connected to different FETs, and the selected channels are switched so that the phase is inverted in the same cycle, so that sensing is always possible.
  • the electrolyte solution A filling the micro chamber and the electrolyte solution B filling the upper chamber are configured to supply different types of electrolyte solutions to the FETs.
  • the micro chamber and the upper chamber may be filled.
  • the supply part which supplies electrolyte solution may be one.
  • the FET of this embodiment it is necessary to cause a concentration difference with respect to a specific ion or a group of ions in the electrolyte solution filling the microchamber and the upper chamber separated by the lipid bilayer membrane.
  • a configuration in which different types of electrolyte solutions are supplied to the respective chambers of the FET, such as the electrolyte solution A filling the microchamber and the electrolyte solution B filling the upper chamber, can realize this.
  • the electrolyte solution to be filled in the microchamber and the upper chamber may be of the same type as long as a difference in ion concentration can be generated between the two electrolyte solutions on both sides of the lipid bilayer after filling the solution.
  • the lipid bilayer to be employed has the function of an ion channel similarly to a general biological cell membrane. Therefore, for example, if a mechanism for replenishing specific ions to the solution in the upper chamber after filling or an active function can be added to the ion channel itself, there is a difference in concentration between the electrolyte solution in the microchamber and the upper chamber separated by the lipid bilayer membrane. Can be generated.
  • a biomimetic molecular detection sensor element and sensor device using a lipid bilayer membrane applicable to a prosthetic organ and a robot detection system, and applicable to an olfactory sensor and a taste sensor. .
  • the FET channel and the lipid bilayer membrane are formed on the same substrate, it is not necessary to secure the likelihood for substrate bonding and bonding as in the past. Therefore, the device size can be reduced. In addition, the number of parts and the number of processes can be reduced, and the cost can be reduced.
  • a micro chamber can be formed by a lithography process in the same manner as the FET fabrication process. Therefore, the density, position, and shape of the micro chamber can be freely formed with high accuracy, and as a result, the detection sensitivity of the device can be improved.

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Abstract

Provided are a micro-sized, highly sensitive, highly reliable sensor element and a sensor device having long service life in which the sensor element is applied. A sensor element provided with a field-effect transistor (FET) formed on an insulated substrate, wherein the sensor element is provided with a first chamber formed above a channel included in the FET, and a second chamber formed above the first chamber, the first chamber and the second chamber are filled with an electrolytic solution, and a lipid bilayer membrane is formed at the boundary between the first chamber and the second chamber.

Description

センサ素子およびセンサデバイスSensor element and sensor device
　本発明は、センサ素子およびセンサデバイスに関し、特に高感度化、高寿命化が可能となるバイオFET(電界効果トランジスタ)を適用したセンサ素子およびセンサデバイスに関するものである。 The present invention relates to a sensor element and a sensor device, and more particularly to a sensor element and a sensor device to which a bio-FET (field effect transistor) capable of achieving high sensitivity and long life is applied.
　嗅覚センサ、味覚センサに適用可能な生体模倣の分子検出のセンサ素子は、補綴器官、ロボットの検知系、センサネットなどへの応用が期待されている。これらセンサを実現するデバイスの一つとしてBio-FET(Field Effect Transistor)が知られている。Bio-FETは、検出対象によって誘発される電位をトランジスタのゲート電極に印加できる構造となっている。対象の検出信号はトランジスタによってその信号強度に応じてアナログ的に増幅されるため、分子検出のセンサ素子として好適なデバイスである。 Sensor elements for biomimetic molecular detection applicable to olfactory sensors and taste sensors are expected to be applied to prosthetic organs, robot detection systems, sensor networks, and the like. Bio-FET (Field-Effect-Transistor) is known as one of devices that realize these sensors. The Bio-FET has a structure in which a potential induced by a detection target can be applied to the gate electrode of the transistor. Since the target detection signal is amplified in an analog manner according to the signal intensity by the transistor, it is a suitable device as a sensor element for molecular detection.
　非特許文献１に開示されているように、Bio-FETは、誘発される電位の発生方法により複数の方式が提案されている。 As disclosed in Non-Patent Document 1, Bio-FET has been proposed with a plurality of methods depending on a method of generating an induced potential.
　例えば、分子選択性を有する抗体や受容体を、ゲート電極やゲート絶縁体に担持したデバイスが広く検討されている。この方式は、電解質中で抗体や受容体に捕獲された検出対象分子の分極により誘起された電位をセンスする方式、もしくは捕獲時の酸化還元作用で発生するH+、OH-を、ゲート電極、ゲート絶縁層に吸着しセンスする方式である。 For example, a device in which an antibody or receptor having molecular selectivity is carried on a gate electrode or a gate insulator has been widely studied. This scheme, H + generated by the redox action of Strategies to sense the induced potential by polarization of the detection target molecules captured by the antibody or receptor in the electrolyte or capture,, OH - a gate electrode, This is a method of adsorbing and sensing the gate insulating layer.
　前者の方式では、分極に伴う電荷分布が局所的なため、トランジスタのチャネルサイズに対し電荷が分布する範囲が小さいと、定量評価が困難になる。また、捕獲された分子が構造揺らぎを持つと、分極による誘起電位の絶対値も揺らぐため、定量評価が困難になる。さらに、検出対象分子の分極が電解質のデバイ長より大きくなると、電解質でのスクリーニングにより、誘発される電位が微小となり検出が困難になる。 In the former method, since the charge distribution accompanying polarization is local, if the range in which the charge is distributed with respect to the channel size of the transistor is small, quantitative evaluation becomes difficult. In addition, if the captured molecules have structural fluctuations, the absolute value of the induced potential due to polarization also fluctuates, making quantitative evaluation difficult. Further, when the polarization of the molecule to be detected becomes larger than the Debye length of the electrolyte, the induced potential becomes small due to the screening with the electrolyte, and the detection becomes difficult.
　後者の方式は、前者の方式における問題は発生しないが、検出対象分子の酸化還元作用を促す抗体、受容体の設計（探索）、担持に関する汎用的な手法がなく、解の有無も検出対象ごとに異なるために、対象が限定されていることが課題となっている。 The latter method does not cause problems in the former method, but there is no general method for designing (searching) or loading antibodies that promote the redox action of the molecules to be detected, and for the presence or absence of a solution for each detection target. Therefore, the subject is limited.
　上述の方式とは別に、検出対象分子をリガンドとする受容体を担持する脂質二重膜で構成された、生体の細胞膜あるいは人工脂質二重膜を電解質で挟み、対象分子が受容体に捕獲された際に誘発される電位を、ゲート電極に印加するFETが提案されている。生体の細胞膜は、ppm、ppb、pptオーダの微量な検出対象に対し、数十mVオーダの膜電位を誘起する。これはトランジスタで検知可能な電位であり、高感度の分子センサデバイスが実現可能となる。 Apart from the above-mentioned method, a biological cell membrane or artificial lipid bilayer membrane composed of a lipid bilayer carrying a receptor whose ligand is the molecule to be detected is sandwiched between electrolytes, and the target molecule is captured by the receptor. There has been proposed an FET that applies a potential induced to a gate electrode. Biological cell membranes induce membrane potentials on the order of tens of millivolts for detection targets as small as ppm, ppb, and ppt. This is a potential detectable by a transistor, and a highly sensitive molecular sensor device can be realized.
　この方式で誘起される電位は、対象分子が受容体に捕獲され発現するイオンチャネルを介し、電解質中のイオンが一定方向に移動した結果生ずる、脂質二重膜両側の二つの電解質のイオン濃度差に由来する。よって、対象分子の構造揺らぎや、電解質のスクリーニングの問題は発生しない。また、原理的には、検知する分子および検出感度は、生体で実現できているものに関しては実現可能である。 The potential induced in this way is the difference in ion concentration between the two electrolytes on both sides of the lipid bilayer, resulting from the movement of ions in the electrolyte in a certain direction through the ion channel where the target molecule is captured and expressed by the receptor. Derived from. Therefore, the structural fluctuation of the target molecule and the problem of electrolyte screening do not occur. Further, in principle, the molecules to be detected and the detection sensitivity can be realized for those that can be realized in a living body.
特開2015-40754号公報JP2015-40754A
　脂質二重膜で構成されたFETの課題は、FET上部の脂質二重膜の安定成膜と、成膜後の寿命である。これまでは、疎水性の樹脂基板に孔を開口し、孔部分に脂質二重膜を形成する方法が主流であった。この方法をBio-FETへ適用する場合、FETと脂質二重膜が異なる基板に作成され、その後、基板どうしを貼り合わせることになる。その結果、貼り合わせ工程の歩留まりを確保する必要性から、デバイスのサイズが大きくなってしまう。また、貼り合わせ工程の歩留まりが、完成品の歩留まりに乗算される結果、デバイスの歩留まりは低下する。さらにFETは一般に、シリコン基板などの樹脂基板とは熱膨張率が大きく異なる基板上に形成されることから、デバイスの信頼性も低下する。 The problem with FETs composed of lipid bilayers is the stable film formation of the lipid bilayer on top of the FET and the lifetime after film formation. Until now, a method of forming holes in a hydrophobic resin substrate and forming a lipid bilayer in the hole portion has been the mainstream. When this method is applied to Bio-FET, the FET and the lipid bilayer are made on different substrates, and then the substrates are bonded together. As a result, the size of the device increases due to the need to ensure the yield of the bonding process. In addition, as a result of the yield of the bonding process multiplied by the yield of the finished product, the device yield decreases. Further, since the FET is generally formed on a substrate having a coefficient of thermal expansion that is significantly different from that of a resin substrate such as a silicon substrate, the reliability of the device is also lowered.
　樹脂基板ではなく、例えば特許文献１に記載の技術ように、ガラスなどの半導体基板と熱膨張率が近い材料基板に、アレイ状の微小孔を開口し、開口部分に脂質二重膜を形成する方法が提案されている。この方法をBio-FETへ適用する場合も、FETと脂質二重膜が異なる基板に作成されるため、貼合せ工程が必須となり、これに伴う上述した問題は依然として残る。さらに、開口孔底部と基板底部の距離が、FETのゲート絶縁層の膜厚として加算されるため、基板の薄膜化が必要になる。距離は10-100nm程度で、かつ均一である必要があり、そのような加工は、従来の加工技術ではほぼ不可能である。 Instead of a resin substrate, for example, as in the technique described in Patent Document 1, an array of micropores is opened in a material substrate having a thermal expansion coefficient close to that of a semiconductor substrate such as glass, and a lipid bilayer membrane is formed in the opening portion. A method has been proposed. Even when this method is applied to Bio-FET, since the FET and the lipid bilayer membrane are formed on different substrates, a bonding step is essential, and the above-described problems still remain. Further, since the distance between the bottom of the opening hole and the bottom of the substrate is added as the film thickness of the gate insulating layer of the FET, it is necessary to reduce the thickness of the substrate. The distance must be about 10-100 nm and uniform, and such processing is almost impossible with conventional processing techniques.
　これらとは別に、脂質二重膜の寿命の問題も大きな課題である。現在のところ、長くとも１週間程度までしかもたず、その後、機能を消失してしまう。長寿命化に向けた研究開発は現在も進行しているが、目覚しい成果は得られていない。 Apart from these, the problem of the lifetime of the lipid bilayer membrane is also a major issue. At present, it is only about one week at the longest, and then the function is lost. Research and development aimed at extending the service life is ongoing, but no remarkable results have been obtained.
　本発明の目的は、微小サイズの、高感度かつ高信頼のセンサ素子を提供することにある。また、本発明の他の目的は、上記センサ素子を適用した長寿命のセンサデバイスを提供することにある。 An object of the present invention is to provide a sensor element having a small size, high sensitivity and high reliability. Another object of the present invention is to provide a long-life sensor device to which the sensor element is applied.
　上記目的を達成するために、本発明は、絶縁基板上に形成された電界効果トランジスタ（FET）を備えるセンサ素子において、前記FETに含まれるチャネルの上方に形成される第１のチャンバと、前記第１のチャンバの上方に形成される第２のチャンバとを備え、前記第１のチャンバと前記第２のチャンバは電解質溶液で満たされており、前記第１のチャンバと前記第２のチャンバの境界に脂質二重膜が形成される構成を採用する。 To achieve the above object, the present invention provides a sensor element including a field effect transistor (FET) formed on an insulating substrate, a first chamber formed above a channel included in the FET, A second chamber formed above the first chamber, wherein the first chamber and the second chamber are filled with an electrolyte solution, and the first chamber and the second chamber A configuration in which a lipid bilayer is formed at the boundary is adopted.
　本発明によれば、デバイスサイズを縮小できる。また部品点数、工程数を削減でき、低コスト化が可能となる。 According to the present invention, the device size can be reduced. In addition, the number of parts and the number of processes can be reduced, and the cost can be reduced.
本実施形態におけるFETの一実施例を示す断面図である。It is sectional drawing which shows one Example of FET in this embodiment. 図１のデバイスの微小チャンバより下部の平面図である。It is a top view below the micro chamber of the device of FIG. 図１のデバイスの上部チャンバより下部の平面図である。FIG. 2 is a plan view below the upper chamber of the device of FIG. 1. 本実施形態におけるデバイスの他の構成を示す、微小チャンバより下部の平面図である。It is a top view below the microchamber which shows other composition of a device in this embodiment. 図４のデバイスの上部チャンバより下部の平面図である。FIG. 5 is a plan view below the upper chamber of the device of FIG. 4. 図４の断面Ｘ１に対応する断面図である。It is sectional drawing corresponding to the cross section X1 of FIG. 図４の断面Ｘ２に対応する断面図である。It is sectional drawing corresponding to the cross section X2 of FIG. 図４の断面Ｙに対応する断面図である。FIG. 5 is a cross-sectional view corresponding to a cross section Y in FIG. 4. 本実施形態におけるデバイスの他の構成を示す断面図である。It is sectional drawing which shows the other structure of the device in this embodiment. 本実施形態におけるデバイスの他の構成を示す断面図である。It is sectional drawing which shows the other structure of the device in this embodiment. 本実施形態におけるデバイスの他の構成を示す断面図である。It is sectional drawing which shows the other structure of the device in this embodiment. 本実施形態におけるFETの脂質二重膜の構成プロセスを説明する図である。It is a figure explaining the composition process of the lipid bilayer membrane of FET in this embodiment. 本実施形態におけるFETの脂質二重膜の構成プロセスを説明する図である。It is a figure explaining the composition process of the lipid bilayer membrane of FET in this embodiment. 本実施形態におけるFETの脂質二重膜の構成プロセスを説明する図である。It is a figure explaining the composition process of the lipid bilayer membrane of FET in this embodiment. 本実施形態におけるFETの脂質二重膜の構成プロセスを説明する図である。It is a figure explaining the composition process of the lipid bilayer membrane of FET in this embodiment. 本実施形態におけるFETの脂質二重膜の表面構造を説明する図である。It is a figure explaining the surface structure of the lipid bilayer membrane of FET in this embodiment. 本実施形態におけるFETの作製プロセスを示す図である。It is a figure which shows the preparation process of FET in this embodiment. 本実施形態におけるFETの作製プロセスを示す図である。It is a figure which shows the preparation process of FET in this embodiment. 本実施形態におけるFETの作製プロセスを示す図である。It is a figure which shows the preparation process of FET in this embodiment. 本実施形態におけるFETの作製プロセスを示す図である。It is a figure which shows the preparation process of FET in this embodiment. 本実施形態におけるFETの作製プロセスを示す図である。It is a figure which shows the preparation process of FET in this embodiment. 本実施形態におけるデバイスの他の構成を示す斜視図である。It is a perspective view which shows the other structure of the device in this embodiment. 図１５（ａ）の断面図である。It is sectional drawing of Fig.15 (a). 本実施形態のFETを適用したセンサデバイスの機能ブロック図である。It is a functional block diagram of the sensor device to which FET of this embodiment is applied. 図１６の構成を持つセンサデバイスのタイミングチャートである。It is a timing chart of the sensor device which has the structure of FIG. 本実施形態のFETを適用したセンサデバイスの、他の構成例を示す機能ブロック図である。It is a functional block diagram which shows the other structural example of the sensor device to which FET of this embodiment is applied. 図１８の構成を持つセンサデバイスのタイミングチャートである。19 is a timing chart of the sensor device having the configuration of FIG.
　以下、本発明を実施するための形態を、実施例を用いて説明する。 Hereinafter, modes for carrying out the present invention will be described using examples.
　図１は、本実施例におけるFETの断面図である。シリコン基板１上に高濃度の不純物層で形成されたソース２、ドレイン３、及びこれらの領域に挟まれたFETチャネル層４が形成され、その上部にゲート絶縁層５、微小チャンバ６を規定する絶縁層７が形成されている。この絶縁層７には、孔もしくは溝が形成されており、微小チャンバ６を規定する。 FIG. 1 is a cross-sectional view of an FET in this embodiment. A source 2 and a drain 3 formed of a high-concentration impurity layer and an FET channel layer 4 sandwiched between these regions are formed on a silicon substrate 1, and a gate insulating layer 5 and a micro chamber 6 are defined above the source 2 and drain 3. An insulating layer 7 is formed. The insulating layer 7 is formed with holes or grooves to define the minute chamber 6.
　微小チャンバ６を規定する孔もしくは溝の上面には、人工もしくは生体の脂質二重膜８が孔もしくは溝に蓋をするように形成され、微小チャンバ６と上部チャンバ９とを分離している。上部チャンバ９は別途設けられた絶縁層などからなるシース１０で規定される。シース１０はゲート絶縁層５、微小チャンバ６を規定する絶縁層と同じ材料の絶縁層で形成できれば、作製工程という観点では効率的であるが、上部チャンバ９は複数のFETで共有することが可能であるので、デバイスのサイズが小さくなったとしても、貼合わせの尤度を確保できる。そのため例えばアクリルなどの有機系樹脂で形成し、後の工程で貼合せる方法を用いても良い。 An artificial or living body lipid bilayer membrane 8 is formed on the upper surface of the hole or groove defining the micro chamber 6 so as to cover the hole or groove, and the micro chamber 6 and the upper chamber 9 are separated. The upper chamber 9 is defined by a sheath 10 made of an insulating layer provided separately. If the sheath 10 can be formed from the same material as the insulating layer that defines the gate insulating layer 5 and the micro chamber 6, it is efficient in terms of manufacturing process, but the upper chamber 9 can be shared by a plurality of FETs. Therefore, even if the size of the device is reduced, the likelihood of pasting can be ensured. Therefore, for example, a method of forming with an organic resin such as acrylic and bonding in a later step may be used.
　微小チャンバ６、および上部チャンバ９には電解質溶液が充填され、生体の細胞内(微小チャンバ６に相当)、細胞外(上部チャンバ９に相当)の環境を再現している。上部チャンバ９にはFETの動作安定化のために参照電極１１が形成される。また、電解質溶液の廃液、充填のために、上部チャンバ９を規定するシース１０には、マイクロ流路１２が少なくとも２流路形成されている。 The microchamber 6 and the upper chamber 9 are filled with an electrolyte solution to reproduce the environment inside the living cells (corresponding to the microchamber 6) and extracellular (corresponding to the upper chamber 9). A reference electrode 11 is formed in the upper chamber 9 to stabilize the operation of the FET. Further, at least two micro-channels 12 are formed in the sheath 10 that defines the upper chamber 9 for waste and filling of the electrolyte solution.
　微小チャンバ６と上部チャンバ９とを分離する脂質二重膜８には、特定の分子に対してイオンチャネルとして働く受容体１３が埋め込まれている。外部より上部チャンバ９に取り込まれた特定の分子が、受容体１３に取り込まれると、これに応じてイオンチャネルが開き、電解質中の特定のイオンが、一方向に輸送される。これにより微小チャンバ６と上部チャンバ９との間にイオン濃度の差が生じ、脂質二重膜８の上下で電位差が生じる。この結果、FETのゲート絶縁層５の上部には、参照電極１１の電位と、上記電位差の和が印加される。この電位差は通常、数十mVオーダとなり、従来のFETで充分検出可能な値である。微小チャンバ６はFETチャネル４の上部を覆うように形成されているため、上記電位差はFETチャネル４全域に印加され、電流経路となる反転層を形成する。 In the lipid bilayer membrane 8 that separates the micro chamber 6 and the upper chamber 9, a receptor 13 that acts as an ion channel for a specific molecule is embedded. When a specific molecule taken into the upper chamber 9 from the outside is taken into the receptor 13, the ion channel is opened accordingly, and a specific ion in the electrolyte is transported in one direction. As a result, a difference in ion concentration occurs between the micro chamber 6 and the upper chamber 9, and a potential difference is generated above and below the lipid bilayer membrane 8. As a result, the sum of the potential of the reference electrode 11 and the potential difference is applied to the upper portion of the gate insulating layer 5 of the FET. This potential difference is usually on the order of several tens of mV, and can be sufficiently detected by a conventional FET. Since the minute chamber 6 is formed so as to cover the upper part of the FET channel 4, the potential difference is applied to the entire region of the FET channel 4 to form an inversion layer serving as a current path.
　従来は、電解質溶液で満たされたチャンバを含む基板と、能動層（FETのソース、ドレイン、チャネルからなる）が形成された基板との貼り合わせの尤度を確保するため、デバイスのサイズは数十μm以下で形成することは技術的に困難であった。しかし、本実施例のデバイス構成を採用することで、少なくとも細胞膜下部の微小チャンバはFETの能動層と同一の基板で、かつ同一のスケールの精度で形成することが可能となる。したがってデバイスサイズを縮小できる。また部品点数、工程数を削減でき、低コスト化が可能となる。 Conventionally, the size of the device is several in order to secure the likelihood of bonding between the substrate containing the chamber filled with the electrolyte solution and the substrate on which the active layer (consisting of the source, drain, and channel of the FET) is formed. It was technically difficult to form with a thickness of 10 μm or less. However, by adopting the device configuration of this embodiment, at least the microchamber below the cell membrane can be formed on the same substrate as the active layer of the FET and with the same scale accuracy. Therefore, the device size can be reduced. In addition, the number of parts and the number of processes can be reduced, and the cost can be reduced.
　またゲート絶縁層５の膜厚は、FETの作製工程の精度で薄膜化できる。ゲート絶縁層５の薄膜化により、FETの増幅率向上、シグナルノイズ低減が可能となり、検出感度が高いセンサデバイスが実現可能となる。 Also, the film thickness of the gate insulating layer 5 can be reduced with the accuracy of the FET manufacturing process. By making the gate insulating layer 5 thinner, it is possible to improve the amplification factor of the FET and reduce the signal noise, thereby realizing a sensor device with high detection sensitivity.
　また、本実施例のデバイス構成では、微小チャンバ６の体積を、FETの作製工程において可能な精度の範囲内で、微小化することが可能である。例えば、典型的には、径もしくは幅が500から数千nm、深さが数千nm程度の孔もしくは溝が形成可能となるが、用途や必要な検知精度に応じて設計すればよい。微小チャンバとすることで、微小チャンバ６と上部チャンバ９間で交換されるイオン量に対する微小チャンバ６の濃度変動量が大きくなり、濃度平衡となるまでの時間が短くなる。その結果電位差が生じる時間も短くなる。そのため、時間応答の速いセンサデバイスが実現可能となる。 Further, in the device configuration of the present embodiment, the volume of the micro chamber 6 can be miniaturized within the accuracy range possible in the FET manufacturing process. For example, typically, a hole or groove having a diameter or width of 500 to several thousand nm and a depth of about several thousand nm can be formed, but it may be designed according to the application and required detection accuracy. By using the micro chamber, the concentration fluctuation amount of the micro chamber 6 with respect to the amount of ions exchanged between the micro chamber 6 and the upper chamber 9 increases, and the time until concentration equilibrium is shortened. As a result, the time during which the potential difference occurs is also shortened. Therefore, a sensor device having a quick time response can be realized.
　図２は、図１における微小チャンバ６より下部のデバイスの平面図である。図２では、説明のためにFETのソース２、ドレイン３、FETチャネル４の透視図としている。図１に示した、微小チャンバ６を規定する孔もしくは溝の領域は、FETチャネル４の上部を覆うように形成されており、FETチャネル４上部の絶縁層７の膜厚は、孔もしく溝が形成されない部分よりも薄くなるよう設計されている。つまりFETのゲート絶縁層７の膜厚は、孔もしくは溝の深さで規定される。 FIG. 2 is a plan view of the device below the microchamber 6 in FIG. In FIG. 2, for the sake of explanation, a perspective view of the FET source 2, drain 3, and FET channel 4 is shown. The hole or groove region defining the micro chamber 6 shown in FIG. 1 is formed so as to cover the upper part of the FET channel 4, and the film thickness of the insulating layer 7 on the FET channel 4 is a hole or groove. It is designed to be thinner than the part where no is formed. That is, the film thickness of the gate insulating layer 7 of the FET is defined by the depth of the hole or groove.
　図３は、上部チャンバ９より下部のデバイスの平面図である。上部チャンバ９と微小チャンバ６を仕切る脂質二重膜８は省略している。上部チャンバ９を規定するシース１０には、マイクロ流路１２が少なくとも２流路形成されている。図１、図３では、マイクロ流路１２の上部をシース１０が覆う構成であるが、溝状に流路を形成した後、別の材料で蓋をするように被覆しても構わない。このマイクロ流路１２の片側には、電解質溶液、脂質溶液、界面活性材などが適宜入れ替わり投入される。そしてもう片側からは、それぞれの溶液が廃棄される。 FIG. 3 is a plan view of the device below the upper chamber 9. The lipid bilayer membrane 8 that partitions the upper chamber 9 and the micro chamber 6 is omitted. The sheath 10 that defines the upper chamber 9 has at least two microchannels 12 formed therein. 1 and 3, the sheath 10 covers the upper part of the microchannel 12. However, after the channel is formed in a groove shape, the microchannel 12 may be covered with another material. An electrolyte solution, a lipid solution, a surfactant, and the like are appropriately exchanged and supplied to one side of the microchannel 12. Each solution is discarded from the other side.
　後で述べるように、このデバイス構成を適用すれば、脂質二重膜の溶解、廃棄、再形成が可能となり、デバイスの実効的な長寿命化を実現できる。 As will be described later, when this device configuration is applied, the lipid bilayer membrane can be dissolved, discarded, and reformed, and the effective life of the device can be increased.
　図４は、図１に示すデバイスとは異なる構成の、微小チャンバより下部の平面図である。図５は、図４に示すデバイスの上部チャンバ９より下部のデバイスの平面図である。図５では、図３と同様、上部チャンバ９と微小チャンバ６を仕切る脂質二重膜８は省略している。 FIG. 4 is a plan view below the microchamber having a configuration different from that of the device shown in FIG. FIG. 5 is a plan view of the device below the upper chamber 9 of the device shown in FIG. In FIG. 5, as in FIG. 3, the lipid bilayer membrane 8 that partitions the upper chamber 9 and the micro chamber 6 is omitted.
　図４に示すように、FETの電流が流れる方向、すなわち断面X1、断面X2の線と平行な方向に、微小チャンバ６を規定する複数個の溝が設けられている。さらに各溝は、少なくともソース２、ドレイン３それぞれの領域の一部を覆い、かつFETチャネル４の一部を覆っている。溝状の微小チャンバ６は、図1の例と比較し、開口面が小さいため、上端面に形成される脂質二重膜８にかかる表面張力が緩和できる。よって安定なデバイスが実現される。 As shown in FIG. 4, a plurality of grooves defining the micro chamber 6 are provided in the direction in which the current of the FET flows, that is, in the direction parallel to the lines of the cross section X1 and the cross section X2. Further, each groove covers at least a part of each region of the source 2 and the drain 3 and a part of the FET channel 4. Compared with the example of FIG. 1, the groove-like microchamber 6 has a smaller opening surface, so that the surface tension applied to the lipid bilayer membrane 8 formed on the upper end surface can be relaxed. Therefore, a stable device is realized.
　また、図５に示すとおり、マイクロ流路１２は、溝の２本の短辺に対向する２面のシース１０の壁面に２個設置されている。本構造とすることで、脂質二重膜形成の際、脂質溶液は、微小チャンバを規定する溝の短辺に平行に流入し、膜面も脂質溶液の流入する先端面に沿って形成される。膜面形成時に膜にかかる表面張力起因の反発力は、長辺で引っ張るよりも短辺で引っ張る方が小さくなるため、本構造を採用することで、脂質二重膜がより安定に成膜可能となる。 In addition, as shown in FIG. 5, two microchannels 12 are installed on the wall surface of the two sheaths 10 facing the two short sides of the groove. With this structure, when forming the lipid bilayer membrane, the lipid solution flows in parallel to the short side of the groove defining the microchamber, and the membrane surface is also formed along the tip surface into which the lipid solution flows. . Since the repulsive force due to surface tension applied to the membrane during membrane surface formation is smaller when it is pulled on the short side than on the long side, this structure makes it possible to form a lipid bilayer membrane more stably. It becomes.
　図６は、図４および図５における断面Ｘ１に対応する断面図、図７は、図４および図５における断面Ｘ２に対応する断面図、図８は、図４および図５における断面Ｙに対応する断面図である。図６、図７ではFETチャネル４の記載を省略している。これらの図に示すように、脂質二重膜８の間に電位差が生じた場合、FETチャネル４のうち、上部に微小チャンバ６が存在する領域のみに、電流経路となるFETチャネル４が形成される。 6 is a cross-sectional view corresponding to the cross section X1 in FIGS. 4 and 5, FIG. 7 is a cross-sectional view corresponding to the cross section X2 in FIGS. 4 and 5, and FIG. 8 corresponds to the cross section Y in FIGS. FIG. 6 and 7, the FET channel 4 is not shown. As shown in these figures, when a potential difference is generated between the lipid bilayer membranes 8, the FET channel 4 serving as a current path is formed only in the region of the FET channel 4 where the micro chamber 6 exists in the upper part. The
　図８に示すように、参照電極１１は、上部チャンバ９の上面を被覆するように形成されており、溝状に開口した開口部１４を備える。開口部１４は、微小チャンバ６の上部に形成される。つまり、開口部１４は、シリコン基板１に対し投影関係となるよう加工されている。開口部１４は外環境につながっており、検出対象の分子は、この開口部１４を介して上部チャンバ９の電解質溶液に溶込む。上述のとおり、検出のためには、対象分子は受容体１３まで運ばれる必要がある。 As shown in FIG. 8, the reference electrode 11 is formed so as to cover the upper surface of the upper chamber 9, and includes an opening 14 opened in a groove shape. The opening 14 is formed in the upper part of the micro chamber 6. That is, the opening 14 is processed so as to have a projection relationship with respect to the silicon substrate 1. The opening 14 is connected to the external environment, and molecules to be detected are dissolved in the electrolyte solution in the upper chamber 9 through the opening 14. As described above, the target molecule needs to be transported to the receptor 13 for detection.
　本実施例に示すデバイス構造を採用すると、参照電極１２は開口部１４を除いて上部チャンバ９を覆うように形成されているので、各微小チャンバ６に対する距離などの位置関係は均一に近づく。また、対象分子が開口部１４から受容体１３まで移動する距離が最短となるレイアウトであるため、均一でかつ応答が早いデバイスを提供することが可能となる。 When the device structure shown in the present embodiment is adopted, the reference electrode 12 is formed so as to cover the upper chamber 9 except for the opening 14, so that the positional relationship such as the distance with respect to each micro chamber 6 approaches uniformly. In addition, since the layout has the shortest distance that the target molecule moves from the opening 14 to the receptor 13, it is possible to provide a uniform and quick response device.
　上記の例では、シリコン基板１上に作成したバルクFET（図６、図８に示す）を例に示したが、例えば図９に示すような、SOI基板６０に作成したFETを採用すると、さらに性能の高いFETを提供できる。図９の例では、シリコン基板１上に作成されたSOI基板６０を能動層に適用している。これにより寄生ダイオードやシリコン基板との間の浮遊容量を抑えられるとともに、デバイスの高速応答、リーク電流抑制が可能になる。 In the above example, the bulk FET (shown in FIGS. 6 and 8) created on the silicon substrate 1 is shown as an example. However, when the FET created on the SOI substrate 60 as shown in FIG. High performance FET can be provided. In the example of FIG. 9, the SOI substrate 60 formed on the silicon substrate 1 is applied to the active layer. As a result, the stray capacitance between the parasitic diode and the silicon substrate can be suppressed, and the high-speed response of the device and the leakage current can be suppressed.
　また基板に電圧を印加できるように構成しておけば、FETの特性調整が可能となる（つまり、バックゲートバイアスを印加できるようになる）ため、デバイスのばらつきを補正することが可能なデバイスが提供可能となる。図９は、図１から図３で示したデバイスへの適用例を示しているが、図４から図８で示したデバイスへも適用可能である。 Also, if the voltage can be applied to the substrate, the FET characteristics can be adjusted (that is, the back gate bias can be applied), so there are devices that can correct device variations. It can be provided. FIG. 9 shows an application example to the device shown in FIGS. 1 to 3, but it can also be applied to the device shown in FIGS. 4 to 8.
　図１０は、図１および図４に示すデバイスとは異なる構成のデバイスの断面図である。図１０では、上部チャンバ９の下部に、少なくとも２個以上のFETが形成され、かつ各FETの上部には、それぞれ微小チャンバ６が形成されており、かつ微小チャンバ６の体積が互いに異なっている。 FIG. 10 is a cross-sectional view of a device having a configuration different from that shown in FIGS. In FIG. 10, at least two or more FETs are formed in the lower part of the upper chamber 9, and the minute chambers 6 are formed in the upper parts of the FETs, and the volumes of the minute chambers 6 are different from each other. .
　前述のとおり、微小チャンバ６を設ける効果の一つは、対象分子が受容体１３に捕捉され、特定イオンチャネルが開くことによる電解質溶液中の濃度変動の時間応答が速くなることであるが、微小チャンバ６の体積が異なると、その応答速度も異なる。定性的には、対象分子の濃度が小さい場合、微小チャンバ６の体積が小さいFETでその応答は良好となり、微小チャンバの体積が大きいFETでは応答は鈍感となる。一方、対象分子の濃度が大きい場合、微小チャンバ６の体積が小さいFETではその応答は飽和状態となり、微小チャンバ６の体積が大きいFETで応答は良好となる。 As described above, one of the effects of providing the micro chamber 6 is that the target molecule is captured by the receptor 13 and the time response of the concentration fluctuation in the electrolyte solution due to the opening of the specific ion channel is accelerated. If the volume of the chamber 6 is different, the response speed is also different. Qualitatively, when the concentration of the target molecule is small, the response is good with an FET with a small volume of the micro chamber 6, and the response is insensitive with an FET with a large volume of the micro chamber. On the other hand, when the concentration of the target molecule is large, the response is saturated in the FET with the small volume of the micro chamber 6, and the response is good with the FET with the large volume of the micro chamber 6.
　図１０に示す構成では、微小チャンバ６の体積が異なる、少なくとも２個以上のFETでデバイスが構成されている。微小チャンバ６の体積は、FETの作製工程の範囲内で自由に設定することができる。したがって極めて検出可能な濃度範囲が広い分子検出デバイスを提供することが可能になる。 In the configuration shown in FIG. 10, the device is configured by at least two or more FETs having different volumes of the micro chamber 6. The volume of the micro chamber 6 can be freely set within the range of the FET manufacturing process. Therefore, it is possible to provide a molecular detection device having a wide detectable concentration range.
　また本実施例に示す構成では、脂質二重膜再構成のために用いられるマイクロ流路対と同一の流路対、あるいは別組のマイクロ流路対を設け、上部チャンバの電解質溶液を循環させる機能を付加することができる。 Further, in the configuration shown in the present embodiment, the same channel pair as the microchannel pair used for lipid bilayer membrane reconstruction or another microchannel pair is provided to circulate the electrolyte solution in the upper chamber. Functions can be added.
　図１１は、図１で示したFETを適用した場合のデバイスの断面図である。なお、図１１の構成は、図１～１０に示した全てのFETに対し適用可能である。上部チャンバ９の電解質溶液を循環させる機能を果たす流路対を、脂質二重膜再構成のための流路対と同一にする場合は、流入側の上流、流出側の下流に選択バルブを設け、流路を分岐すればよい。電解質溶液は、電解質の循環装置２０によって上部チャンバ９と取り込みチャンバ２１の間を循環する。電解質の循環装置２０には、μ-TAS技術などで採用されているマイクロポンプや、MEMSなどを採用することができる。 FIG. 11 is a cross-sectional view of the device when the FET shown in FIG. 1 is applied. The configuration of FIG. 11 can be applied to all the FETs shown in FIGS. When the channel pair that performs the function of circulating the electrolyte solution in the upper chamber 9 is made the same as the channel pair for lipid bilayer membrane reconstruction, a selection valve is provided upstream on the inflow side and downstream on the outflow side. The flow path may be branched. The electrolyte solution circulates between the upper chamber 9 and the intake chamber 21 by the electrolyte circulation device 20. The electrolyte circulation device 20 may employ a micropump employed in the μ-TAS technology or the like, MEMS, or the like.
　本構成を採用した場合、取り込みチャンバ２１の設計位置や設計面積は、FET、微小チャンバ、及び上部チャンバの位置やサイズとは独立に、自由に設計することが可能となる。とくに気相中の分子を検出する場合に、取り込み口２２の面積拡大や、効率の良い形状レイアウトが可能となり、検出感度が極めて高いデバイスが実現可能となる。 When this configuration is adopted, the design position and design area of the intake chamber 21 can be freely designed independently of the positions and sizes of the FET, the micro chamber, and the upper chamber. In particular, when detecting molecules in the gas phase, the area of the intake port 22 can be enlarged and an efficient shape layout can be realized, and a device with extremely high detection sensitivity can be realized.
　図１２は、脂質二重膜の再構成の手順を説明する図である。 FIG. 12 is a diagram for explaining the procedure for reconstitution of the lipid bilayer membrane.
　空の状態のデバイス（図１２(a)）に、マイクロ流路１２を介して、微小チャンバ６に充填する電解質溶液２３を導入する(図１２(b))。続いて、マイクロ流路１２を介して、脂質二重膜を構成する脂質、受容体たんぱく質を含有する脂質性溶液２４を上部チャンバ９に導入する(図１２(c))。このとき、微小チャンバ６の内部には電解質溶液２３が残留し、電解質溶液２３と脂質性溶液２４との間に脂質一重膜２５が形成される。脂質一重膜２５は、親水基を電解質溶液２３側に、疎水基を脂質性溶液２４側に向けて配列する。電解質溶液２３と脂質性溶液２４の境界部、すなわち脂質性一重膜２５の形成位置は、系の界面エネルギーが最小となることから、微小チャンバ開口面のエッジ部を起点に開口面に沿って安定に形成される(図１２(c))。 The electrolyte solution 23 filling the micro chamber 6 is introduced into the empty device (FIG. 12 (a)) through the microchannel 12 (FIG. 12 (b)). Subsequently, a lipidic solution 24 containing a lipid constituting the lipid bilayer membrane and a receptor protein is introduced into the upper chamber 9 through the microchannel 12 (FIG. 12 (c)). At this time, the electrolyte solution 23 remains inside the micro chamber 6, and a lipid single membrane 25 is formed between the electrolyte solution 23 and the lipidic solution 24. The lipid single membrane 25 is arranged with the hydrophilic group facing the electrolyte solution 23 and the hydrophobic group facing the lipidic solution 24. The boundary between the electrolyte solution 23 and the lipidic solution 24, that is, the position where the lipidic single membrane 25 is formed is stable along the opening surface starting from the edge of the microchamber opening surface because the interfacial energy of the system is minimized. (FIG. 12C).
　次に、マイクロ流路１２を介して、上部チャンバ９に充填する電解質溶液２６を充填する。このとき微小チャンバ６の開口面では、脂質性一重膜２５の疎水基を被覆するように、二層目脂質分子が配列し、脂質二重膜８が形成される(図１２(d))。 Next, the electrolyte solution 26 that fills the upper chamber 9 is filled through the micro flow path 12. At this time, on the opening surface of the micro chamber 6, the second-layer lipid molecules are arranged so as to cover the hydrophobic group of the lipidic single membrane 25, and the lipid bilayer membrane 8 is formed (FIG. 12 (d)).
　脂質二重膜８に埋め込まれる受容体分子などのタンパク質は、その分子構造、界面エネルギーの安定度にしたがって、脂質一重層２５が形成されるタイミングから、脂質二重層８が形成されるタイミングの間に随時取り込まれる。このように、受容体分子が自然に埋め込まれる現象を利用する以外に、界面活性材や熱振動を用いて、受容体分子を積極的に埋め込む方法もある。 A protein such as a receptor molecule embedded in the lipid bilayer membrane 8 is between the timing at which the lipid monolayer 25 is formed and the timing at which the lipid bilayer 8 is formed according to the stability of the molecular structure and interfacial energy. Is taken in from time to time. As described above, there is a method of positively embedding receptor molecules using a surfactant or thermal vibration, in addition to utilizing a phenomenon in which receptor molecules are naturally embedded.
　一旦形成された脂質二重膜８を除去する際には、マイクロ流路１２を介して、界面活性剤を導入する。これにより脂質二重膜８を構成する脂質分子は、電解質溶液中に溶出する。その後、微小チャンバ６に充填する電解質溶液２３を導入し、既充填の溶液を、もう片方のマイクロ流路１２を介して廃液することで脂質分子を除去する。ここで、脂質分子の溶出を加速するために、熱振動を与えてもよい。 When removing the lipid bilayer membrane 8 once formed, a surfactant is introduced through the microchannel 12. Thereby, lipid molecules constituting the lipid bilayer membrane 8 are eluted in the electrolyte solution. Thereafter, the electrolyte solution 23 to be filled in the micro chamber 6 is introduced, and the lipid molecules are removed by draining the already filled solution through the other microchannel 12. Here, thermal vibration may be applied in order to accelerate the elution of lipid molecules.
　図１１における構成において、図１３（ａ）に示すように、上部チャンバ９の下に、シリコン基板１側から親水性絶縁層２７、疎水性絶縁層２８、及び親水性絶縁層２９の順に積層した構造を採用することで、微小チャンバ６の開口面に、より安定に、再現性よく脂質二重膜８を形成することができるようになる。ここで、疎水性絶縁層２８及び親水性絶縁層２９を、１から２nmの膜厚で形成することが望ましい。 In the configuration shown in FIG. 11, as shown in FIG. 13A, a hydrophilic insulating layer 27, a hydrophobic insulating layer 28, and a hydrophilic insulating layer 29 are stacked in this order from the silicon substrate 1 under the upper chamber 9. By adopting the structure, the lipid bilayer membrane 8 can be formed more stably and reproducibly on the opening surface of the micro chamber 6. Here, it is desirable to form the hydrophobic insulating layer 28 and the hydrophilic insulating layer 29 with a film thickness of 1 to 2 nm.
　図１３（ｂ）は、微小チャンバ６の端部を拡大した図である。図１３（ｂ）に示すように、脂質二重膜８は、微小チャンバ６の端部を起点に形成されるが、図１３（ａ）に示す積層構造を適用することで、脂質分子３０中の脂質疎水基３１は疎水性絶縁層２８に、脂質親水基３２は親水性絶縁層２７、２９に引き寄せられ、脂質二重膜８の起点となる。脂質分子３０は鎖状分子であり、その多くは数nmの長さとなるので、上述したとおり、疎水性絶縁層２８及び親水性絶縁層２９の膜厚を１から２nmで積層することが望ましい。 FIG. 13B is an enlarged view of the end of the micro chamber 6. As shown in FIG. 13 (b), the lipid bilayer membrane 8 is formed starting from the end of the microchamber 6. By applying the laminated structure shown in FIG. The lipid hydrophobic group 31 is attracted to the hydrophobic insulating layer 28, and the lipid hydrophilic group 32 is attracted to the hydrophilic insulating layers 27 and 29, and becomes the starting point of the lipid bilayer membrane 8. Since the lipid molecule 30 is a chain molecule, most of which has a length of several nm, as described above, it is desirable that the hydrophobic insulating layer 28 and the hydrophilic insulating layer 29 are laminated with a thickness of 1 to 2 nm.
　図１３の構成において、親水性絶縁材料としては例えばシリコン酸化膜などが、疎水性絶縁材料としては例えばモノシランと窒素を原料とした化学気相成長法を適用したシリコン窒化膜などがある。材料の選択により、図１３に示す構造は実現できるが、積層膜に一般的な表面処理を適用するか、もしくは積層膜の原料や成膜条件を制御することで、同一構成材料を用いた薄膜においても、膜の疎水化、親水化は比較的容易に制御できる。また数nm単位の膜厚制御は、例えば化学気相成長法や物理気相成長法において成膜時間を制御することで可能となり、一般的なFET形成工程においては特に困難な工程ではない。 In the configuration of FIG. 13, the hydrophilic insulating material includes, for example, a silicon oxide film, and the hydrophobic insulating material includes, for example, a silicon nitride film to which a chemical vapor deposition method using monosilane and nitrogen as raw materials is applied. Although the structure shown in FIG. 13 can be realized by selecting the material, a thin film using the same constituent material can be realized by applying a general surface treatment to the laminated film or by controlling the raw material and film forming conditions of the laminated film. However, the hydrophobicity and hydrophilicity of the membrane can be controlled relatively easily. The film thickness can be controlled in units of several nanometers by controlling the film formation time in, for example, chemical vapor deposition or physical vapor deposition, and is not particularly difficult in a general FET formation process.
　次に、本実施例のデバイス構造の形成方法を、図１に示したデバイスの例を形成する工程例で説明する。FET形成工程の詳細は、公知のMOS形成プロセスに準拠したものであり、よく知られている技術である。シリコン基板表面のFET能動層の形成方法の詳細は多くの文献があるため、それらを参照されたい。下記ではその形成法の一例を示す。 Next, the method for forming the device structure of the present embodiment will be described with reference to a process example for forming the device example shown in FIG. The details of the FET forming process are based on a well-known MOS forming process and are well-known techniques. For details of the method of forming the FET active layer on the surface of the silicon substrate, refer to them because there are many documents. Below, an example of the formation method is shown.
　まず、シリコン基板１の表面に、必要に応じてウェルを形成する。続いてLOCOS(Local Oxidation of Silicon)工程もしくはSTI(Shallow Trench Isolation)工程を用いて素子分離を行う。以下、図１４では、ウェル層、および素子分離の絶縁層に関しては表記を省略する。 First, a well is formed on the surface of the silicon substrate 1 as necessary. Subsequently, element isolation is performed using a LOCOS (Local Oxidation of Silicon) process or an STI (Shallow Trench Isolation) process. Hereinafter, in FIG. 14, the description of the well layer and the element isolation insulating layer is omitted.
　次に、熱酸化もしくは化学気相成長法を用いて、ソース・ドレイン形成用酸化膜３３を成膜する（図１４（ａ））。この後、必要に応じて、FETの閾値制御用の不純物をイオン注入法により基板表面に導入する。ソース・ドレイン形成用酸化膜３３の厚さは、イオン注入法を用いた不純物導入が最適となるように設定される。 Next, a source / drain forming oxide film 33 is formed by thermal oxidation or chemical vapor deposition (FIG. 14A). Thereafter, if necessary, impurities for controlling the threshold value of the FET are introduced into the substrate surface by an ion implantation method. The thickness of the source / drain forming oxide film 33 is set so that the impurity introduction using the ion implantation method is optimized.
　次に、ホト工程を用いて、ソース・ドレイン領域を除いた領域を、ホトレジスト３４で被覆する（図１４（ｂ））。その後イオン注入法により、ソース・ドレイン領域に不純物を導入し、不純物導入層３５を形成する。N型のFETの場合、導入する不純物は、例えばリン、ヒ素などの元素であり、P型のFETの場合、導入する不純物は、例えばボロン、アルミなどの元素である。 Next, using a photo process, the region excluding the source / drain regions is covered with a photoresist 34 (FIG. 14B). Thereafter, impurities are introduced into the source / drain regions by ion implantation to form an impurity introduction layer 35. In the case of an N-type FET, the impurity to be introduced is an element such as phosphorus or arsenic. In the case of a P-type FET, the impurity to be introduced is an element such as boron or aluminum.
　次に、ホトレジスト３４、ソース・ドレイン形成用酸化膜３３を除去した後、厚い絶縁層７を形成する（図１４（ｃ））。この膜は成膜時間を短縮するために、例えば、化学気相成長法などが用いられる。膜厚は微小チャンバの大きさに合わせて制御するが、典型的な値としては１μmから１０μmである。 Next, after removing the photoresist 34 and the source / drain forming oxide film 33, a thick insulating layer 7 is formed (FIG. 14C). For example, a chemical vapor deposition method is used to shorten the film formation time. The film thickness is controlled in accordance with the size of the micro chamber, but a typical value is 1 μm to 10 μm.
　絶縁層7の膜質（緻密度、欠陥密度など）は、緻密すなわち高密度であって、かつ欠陥密度が小さい高品質なものであることが望ましい。特にFETのゲート絶縁層として使用される場合、膜質はFETのスイッチ特性に敏感に作用するため、高品質であることは必須である。しかし、膜厚が１μmから１０μmと厚い場合、成膜時間は長くなるため、コストや製造時間の観点から、絶縁層7全体を高品質とすることは現実的ではない。 It is desirable that the film quality (density, defect density, etc.) of the insulating layer 7 is dense, that is, high-quality and has a low defect density. In particular, when used as a gate insulating layer of an FET, the film quality is sensitive to the switching characteristics of the FET, so that high quality is essential. However, when the film thickness is as thick as 1 μm to 10 μm, the film formation time becomes long. Therefore, it is not realistic to make the entire insulating layer 7 high in terms of cost and manufacturing time.
　そこで、コストや製造時間を考慮した場合、絶縁層７を、膜質が均質ではない膜として成膜してもよい。例えば、ゲート絶縁膜の機能を担う絶縁層7の下層部を高密度（緻密）で欠陥密度の小さな高品質な膜で構成し、絶縁層の7上層部を成膜速度が速い（下層部よりも低密度な）膜で構成する。 Therefore, in consideration of cost and manufacturing time, the insulating layer 7 may be formed as a film having a non-homogeneous film quality. For example, the lower layer part of the insulating layer 7 that functions as a gate insulating film is composed of a high-quality film with high density (dense) and small defect density, and the upper layer part of the insulating layer 7 has a higher deposition rate (than the lower layer part). (Also low density).
　一般に、成膜時間が短い酸化膜は膜質が悪く、FETのゲート絶縁層として適当ではない。したがって、厚い絶縁層を形成する前に、FETのゲート絶縁層用に１０nm程度の熱酸化膜を形成しておくことが望ましい。このように形成することにより、FETのチャネルが接する部分の絶縁層は、高密度で良好な絶縁層となる。また、良好なゲート絶縁層が得られるだけではなく、後述する微小チャンバの加工の際の、加工レート差すなわち選択比を確保できることにもなり、ゲート絶縁層の膜厚の精度確保が可能になる。 In general, an oxide film having a short film formation time has poor film quality and is not suitable as a gate insulating layer of an FET. Therefore, it is desirable to form a thermal oxide film of about 10 nm for the gate insulating layer of the FET before forming the thick insulating layer. By forming in this way, the portion of the insulating layer in contact with the channel of the FET becomes a high density and good insulating layer. Further, not only a good gate insulating layer can be obtained, but also a processing rate difference, that is, a selection ratio can be ensured when processing a micro chamber described later, and the accuracy of the film thickness of the gate insulating layer can be ensured. .
　さらに、例えば熱酸化膜で形成したゲート絶縁層の上部に、シリコン窒化膜を数nmから数十nm追加成膜することで、選択比をさらに大きく確保できる。上記では、ソース・ドレイン形成用酸化膜を除去することとしたが、この酸化膜が熱酸化などで形成され、FETのゲート絶縁層として充分適用できる場合には、この酸化膜を除去せず、その上に厚い絶縁層を形成してもよい。 Further, for example, a silicon nitride film is additionally formed on the gate insulating layer formed of a thermal oxide film, for example, by several nm to several tens of nm, thereby further ensuring a high selection ratio. In the above, the source / drain forming oxide film is removed, but when this oxide film is formed by thermal oxidation or the like and can be sufficiently applied as a gate insulating layer of an FET, this oxide film is not removed, A thick insulating layer may be formed thereon.
　次に、リソグラフィー工程を用いて、微小チャンバ６を加工する（図１４（ｄ））。図１４（ｄ）では、ホトレジスト３６で加工形状を制御している。ホトレジストで被覆されない領域を異方性のドライエッチングで加工し、孔もしくは溝を形成する。必要に応じて、より選択比が取れる保護膜をホトレジストの下部に形成、加工してもよい。ゲート絶縁層の膜質、膜厚は、FETの制御性と均一性を決める因子となるため、これらを制御することは極めて重要になる。 Next, the micro chamber 6 is processed using a lithography process (FIG. 14D). In FIG. 14D, the processing shape is controlled by the photoresist 36. Regions not covered with the photoresist are processed by anisotropic dry etching to form holes or grooves. If necessary, a protective film with a higher selectivity may be formed and processed under the photoresist. Since the film quality and film thickness of the gate insulating layer are factors that determine the controllability and uniformity of the FET, it is extremely important to control them.
　上述したとおり、シリコン基板と厚い絶縁層との間に高品質な絶縁層や、加工の際の選択比が取れる材料を成膜しておくことにより、ゲート絶縁層の膜質、微小チャンバ形成後のゲート絶縁層の膜厚制御性は向上する。 As described above, by forming a high-quality insulating layer between the silicon substrate and the thick insulating layer, or a material that can be selected at the time of processing, the film quality of the gate insulating layer, the micro chamber after the formation The film thickness controllability of the gate insulating layer is improved.
　次に、ホトレジスト３６や、保護膜を除去した後、本基板に、別工程で加工されたマイクロ流路１２、参照電極１１、マイクロポンプや、MEMSが組込まれた筐体部３７を貼り合せる(図１４（e）)。マイクロ流路１２は、筐体側壁３８に少なくとも１対、２本形成されている。筐体蓋部３９には参照電極１１が埋め込まれ、外部から上部チャンバ側電解質溶液２６に電圧を印加できるよう構成されている。 Next, after removing the photoresist 36 and the protective film, the micro-channel 12, the reference electrode 11, the micro-pump, and the casing 37 in which the MEMS is incorporated are bonded to the substrate. FIG. 14 (e)). At least one and two microchannels 12 are formed on the housing side wall 38. The reference electrode 11 is embedded in the housing lid portion 39 so that a voltage can be applied to the upper chamber side electrolyte solution 26 from the outside.
　上部チャンバ９に外界より分子を導入する方法としては、上述のように循環系で導入する方法と、直接上部チャンバ９に引き込む方法とがある。後者の場合は、分子導入のための微細孔が筐体蓋部３９に多数形成される。 As a method of introducing molecules into the upper chamber 9 from the outside, there are a method of introducing them in the circulation system as described above, and a method of drawing them directly into the upper chamber 9. In the latter case, a large number of fine holes for introducing molecules are formed in the housing lid part 39.
　筐体を構成する材料は、微小チャンバと同じ厚膜の酸化膜や、アクリルなどの有機系の絶縁材料などがある。前者の材料（微小チャンバと同じ厚膜の酸化膜）を採用すると、FET形成工程で筐体の側壁まで一括加工が可能となり、貼合わせ精度の問題から解放される。この場合、上部チャンバも含めた微細化が可能となり、複数種の検出対象を検知可能な微小センサモジュールの提供が可能となる。また、後者の材料（アクリルなどの有機系の絶縁材料）を採用し、貼合わせ尤度を考慮して、大きめに上部チャンバを形成したとしても、本実施例で実現できる主要な効果は、微小チャンバの存在によってもたらされるため、本実施例で得られる利益を享受することができる。 The material constituting the housing includes an oxide film having the same thickness as the microchamber and an organic insulating material such as acrylic. If the former material (an oxide film with the same thickness as that of the micro chamber) is used, it is possible to perform batch processing up to the side wall of the housing in the FET forming process, and it is freed from the problem of bonding accuracy. In this case, miniaturization including the upper chamber is possible, and a micro sensor module capable of detecting a plurality of types of detection objects can be provided. Moreover, even if the latter material (organic insulating material such as acrylic) is used and the upper chamber is formed in consideration of the bonding likelihood, the main effect that can be realized in this embodiment is very small. Since it is brought about by the presence of the chamber, the benefits obtained in this embodiment can be enjoyed.
　例えばセンサアレイのように複数のFETで構成されるセンサモジュールの場合には、例えば図１５（ａ）のように、１個の大きな上部チャンバ９でまとめて被覆することが可能である。図１５（a）は、上部チャンバ９の筐体部を仮想的に開いて、デバイスを俯瞰した図である。１個の大きな上部チャンバに対応して１８個の微小チャンバ６が開口し、それぞれの下部にFETが形成されている。 For example, in the case of a sensor module composed of a plurality of FETs such as a sensor array, for example, as shown in FIG. FIG. 15A is a diagram in which the device of the upper chamber 9 is virtually opened to look down on the device. Eighteen micro-chambers 6 are opened corresponding to one large upper chamber, and FETs are formed in the respective lower portions.
　図１５(b)は、図１５(a)に示す破線に沿った面に対するデバイス断面図である。STI４０で素子分離されたFETが６個配置され、それぞれのFETの上部に微小チャンバ６が形成されている。FETのソース、ドレインは、それぞれソース側ビア４１、ドレイン側ビア４２を介して、上部に形成される配線に電気的に接続される。上部チャンバ９は共通で、マイクロ流路１２、参照電極１１とともに筐体部３７に形成されている。筐体部３７は、例えばアクリル樹脂などの有機系絶縁材料で構成され、FETが形成されたシリコン基板と貼り合わされている。参照電極１１は、筐体蓋部３９に形成された配線を介し、例えばソース側配線と電気的に接続されている。アレイを構成するFETの数は、上部チャンバ９の占有面積に収まる限り自由に設定できる。 FIG. 15 (b) is a device cross-sectional view with respect to the plane along the broken line shown in FIG. 15 (a). Six FETs separated by the STI 40 are arranged, and a micro chamber 6 is formed above each FET. The source and drain of the FET are electrically connected to the wiring formed in the upper part through the source side via 41 and the drain side via 42, respectively. The upper chamber 9 is common and is formed in the casing 37 together with the microchannel 12 and the reference electrode 11. The casing 37 is made of an organic insulating material such as acrylic resin, and is bonded to a silicon substrate on which an FET is formed. The reference electrode 11 is electrically connected to, for example, a source side wiring through a wiring formed on the housing lid portion 39. The number of FETs constituting the array can be freely set as long as it falls within the area occupied by the upper chamber 9.
　また、図１５では参照電極１１を筐体蓋部３９の中央に設ける例を示したが、上部チャンバ９の上面全面に設けたり、メッシュ形状になるよう設けたりすることも可能である。このようにすることで電界分布がセンサアレイ領域で均一となり、感度分布が小さいセンサ群で構成されるセンサアレイを提供することが可能となる。 FIG. 15 shows an example in which the reference electrode 11 is provided in the center of the casing lid portion 39, but it is also possible to provide the reference electrode 11 on the entire upper surface of the upper chamber 9 or in a mesh shape. By doing so, it is possible to provide a sensor array including a sensor group in which the electric field distribution is uniform in the sensor array region and the sensitivity distribution is small.
　図１６は、図１、図６、図８～１０、図１５等に示したFETを適用したセンサデバイスの機能ブロック図である。FETもしくはFETアレイに形成されたマイクロ流路１２に、微小チャンバ６を満たす電解質溶液Ａ（図１２（ｂ）における電解質溶液２３）を供給する供給部５０、上部チャンバ９を満たす電解質溶液Ｂ（図１２（ｂ）における電解質溶液２６）を供給する供給部５１と、脂質二重膜の構成成分となる脂質溶液（図１２（ｃ）における脂質性溶液２４）を供給する供給部５２と、脂質二重膜を溶出する界面活性剤溶液を供給する供給部５３と、溶出された脂質二重膜を含む廃棄液体を回収(再生)する廃液部５４と、供給または廃棄すべき液体の種類、および流経路を制御するためのバルブ群と、これらの各部を制御するための制御部５５で構成されている。 FIG. 16 is a functional block diagram of a sensor device to which the FET shown in FIG. 1, FIG. 6, FIG. 8 to FIG. Supply unit 50 for supplying electrolyte solution A (electrolyte solution 23 in FIG. 12B) filling microchamber 6 to microchannel 12 formed in the FET or FET array, and electrolyte solution B (see FIG. 12) filling upper chamber 9 12 (b), a supply unit 51 for supplying the electrolyte solution 26), a supply unit 52 for supplying a lipid solution (lipidic solution 24 in FIG. 12 (c)) as a constituent of the lipid bilayer, A supply unit 53 that supplies a surfactant solution that elutes the bilayer membrane, a waste liquid unit 54 that collects (regenerates) the waste liquid containing the eluted lipid bilayer membrane, the type and flow of the liquid to be supplied or discarded It consists of a valve group for controlling the path and a control unit 55 for controlling these parts.
　図１６ではこれに加えて、電解質溶液Ｂに検出対象の分子を外環境から取込み、FETへ誘導するための循環部５６が付加されているが、これは必要に応じて付加される。 In FIG. 16, in addition to this, a circulation part 56 for taking the molecules to be detected from the external environment into the electrolyte solution B and guiding them to the FET is added, but this is added as necessary.
　センサデバイスを図１６に示す構成にすると、脂質二重膜を適時に廃棄または再構成できるため、劣化耐性のよい長寿命なデバイスを提供できるようになる。 When the sensor device is configured as shown in FIG. 16, the lipid bilayer membrane can be discarded or reconfigured in a timely manner, so that a long-life device with good deterioration resistance can be provided.
　図１７は、図１６に示す機能ブロック図を有するセンサデバイスの動作を示すタイミングチャートである。縦軸は、機能動作と機能停止をそれぞれ１値と０値で表したもので、横軸に時間をとり、経時推移を表している。 FIG. 17 is a timing chart showing the operation of the sensor device having the functional block diagram shown in FIG. The vertical axis represents the function operation and the function stop by 1 value and 0 value, respectively, and the horizontal axis represents time, and represents the change over time.
　まず、電解質溶液Ａを、マイクロ流路１２を介して微小チャンバ６と上部チャンバ９に充填する。充填の際、廃液部５４のバルブは閉止するが、あえて開放することにより、廃液をしながら充填を行ってもよい。そうすることで、チャンバ内を電解質溶液Ａでパージ、洗浄できる。続いて脂質溶液２４を導入する。この際、微小チャンバ６に充填された電解質溶液Ａは残存し、脂質溶液２４との界面に脂質一重膜２５を形成する。 First, the electrolyte solution A is filled into the micro chamber 6 and the upper chamber 9 through the micro flow path 12. At the time of filling, the valve of the waste liquid part 54 is closed, but filling may be performed while opening the waste liquid by deliberately opening. By doing so, the inside of the chamber can be purged and cleaned with the electrolyte solution A. Subsequently, the lipid solution 24 is introduced. At this time, the electrolyte solution A filled in the microchamber 6 remains, and a lipid monolayer 25 is formed at the interface with the lipid solution 24.
　次に、電解質溶液Ｂを上部チャンバ９に導入する。この際、電解質溶液Ｂは脂質溶液２４を押し出しながら廃液系５４側へ進むが、その境界面と脂質一重膜２５の接線上では、脂質一重膜２５の疎水基と、脂質溶液２４を構成する脂質分子の疎水基が向かい合うように配列し、接線の移動方向とは反対側に脂質二重膜を形成していく。 Next, the electrolyte solution B is introduced into the upper chamber 9. At this time, the electrolyte solution B advances to the waste liquid system 54 side while extruding the lipid solution 24. On the boundary surface and the tangent line of the lipid single membrane 25, the lipid group constituting the lipid solution 24 and the hydrophobic group of the lipid single membrane 25 are formed. The molecules are arranged so that the hydrophobic groups face each other, and a lipid bilayer is formed on the side opposite to the tangential movement direction.
　電解質溶液Ｂが上部チャンバ９に充填された後、供給部５０～５３と廃液部５４のバルブを閉止し、FET４９、および循環部５６（設置している場合）を動作させ、分子センシングを行う。設定した分子センシング時間を経た後、FET４９、および循環部５６（設置している場合）を停止させ、循環部５６のバルブを全て閉止する。その後、界面活性剤溶液を供出する供給部５３と廃液部５４のバルブを開放し、電解質溶液Ａ、Ｂ、脂質二重膜を溶出、廃棄する。 After the electrolyte solution B is filled in the upper chamber 9, the valves of the supply parts 50 to 53 and the waste liquid part 54 are closed, and the FET 49 and the circulation part 56 (when installed) are operated to perform molecular sensing. After the set molecular sensing time, the FET 49 and the circulation unit 56 (if installed) are stopped, and all the valves of the circulation unit 56 are closed. Thereafter, the valves of the supply unit 53 for supplying the surfactant solution and the waste liquid unit 54 are opened, and the electrolyte solutions A and B and the lipid bilayer membrane are eluted and discarded.
　次に、再び電解質溶液Ａを導入、同じシーケンスを経て脂質二重膜を再構成する。 Next, electrolyte solution A is introduced again, and the lipid bilayer membrane is reconfigured through the same sequence.
　電解質溶液Ａ、Ｂのチャンバへの充填、残留や、脂質一重膜、二重膜の形成、脂質膜の廃棄に関しては、原料溶液、廃液の流量制御が重要になる。これらの制御は、制御部によって、例えば配管に設置されたMFC（Mass Flow Controller）で溶液の流量を制御される。バルブ群も同様に、制御部によって開放、閉止を制御される。 Electrochemical solution A and B chamber filling, residue, formation of lipid monolayers and bilayers, and disposal of lipid membranes are important in controlling the flow rate of the raw material solution and waste solution. In these controls, the flow rate of the solution is controlled by the control unit, for example, with an MFC (Mass Flow Controller) installed in the pipe. Similarly, the opening and closing of the valve group is controlled by the control unit.
　図１６に示す構成のセンサデバイスでは、電解質溶液Ａ、Ｂ、脂質二重膜の溶出、廃棄と、脂質二重膜再構成を行っている間は、分子センシングができない。この場合、センサデバイスを図１８に示す構成とすることによって、常にセンシングが可能なデバイスを提供することが可能となる。 In the sensor device having the configuration shown in FIG. 16, molecular sensing is not possible during the elution and disposal of the electrolyte solutions A and B, the lipid bilayer membrane, and the lipid bilayer membrane reconfiguration. In this case, the sensor device having the configuration shown in FIG. 18 can provide a device that can always perform sensing.
　図１８では、供給部、廃棄部、制御部の機能ブロックは図１６と同様であるが、同一構造のFETセンサが２個（ＡとＢ）、選択バルブが２種（選択バルブ１と２）追加されている。適宜、選択バルブを作動させ流路を切り替えることで、各FETのセンシング、及び脂質二重膜の再構成のシーケンスを、異なるタイミングで実行させることによって、センサデバイスが常にセンシングを行うことが可能である。 In FIG. 18, the functional blocks of the supply unit, the disposal unit, and the control unit are the same as in FIG. 16, but two FET sensors with the same structure (A and B) and two types of selection valves (selection valves 1 and 2). Have been added. By appropriately operating the selection valve and switching the flow path, the sensor device can always perform sensing by executing the sensing sequence of each FET and the lipid bilayer reconfiguration sequence at different timings. is there.
　図１９は、図１８に示す機能ブロック図を有するセンサデバイスの動作を示すタイミングチャートである。選択バルブ１の切り換えによって、動作させるFETを選択し、選択バルブ２の切り換えによって、脂質二重膜の再構成を行うFETを選択する。選択バルブ１と２とは、互いに異なるFETへ繋がるマイクロ流路を選択しており、同一周期で位相が反転する形で選択する流路を切り替えるため、常にセンシングが可能になる。 FIG. 19 is a timing chart showing the operation of the sensor device having the functional block diagram shown in FIG. The FET to be operated is selected by switching the selection valve 1, and the FET for reconfiguring the lipid bilayer membrane is selected by switching the selection valve 2. The selection valves 1 and 2 select micro-channels connected to different FETs, and the selected channels are switched so that the phase is inverted in the same cycle, so that sensing is always possible.
　脂質二重膜は劣化するため、図１９では、可能な限りFETセンサ動作の直前で膜の再構成を行う例としたが、別のFETセンサの動作中の時間であれば、どのタイミングで膜の再構成を行ってもよい。また、ここではFETセンサが２個で構成されている例を示したが、２個以上のFETセンサでも、選択バルブを適宜追加すれば、同様の構成を実現できる。 Since the lipid bilayer membrane deteriorates, in FIG. 19, the membrane is reconfigured as much as possible immediately before the FET sensor operation. However, at any timing during the operation of another FET sensor, at any timing May be reconfigured. In addition, although an example in which two FET sensors are configured is shown here, a similar configuration can be realized with two or more FET sensors by adding a selection valve as appropriate.
　図１６と図１８では、微小チャンバに充填する電解質溶液Ａと、上部チャンバに充填する電解質溶液Ｂは、異なる種類の電解質溶液をそれぞれFETに供給する構成を採用したが、同じ種類の電解質溶液を微小チャンバと上部チャンバに充填する構成でもよい。その場合は、電解質溶液を供給する供給部は一つでよい。 In FIG. 16 and FIG. 18, the electrolyte solution A filling the micro chamber and the electrolyte solution B filling the upper chamber are configured to supply different types of electrolyte solutions to the FETs. The micro chamber and the upper chamber may be filled. In that case, the supply part which supplies electrolyte solution may be one.
　本実施例のFETでは、脂質二重膜で隔てられた微小チャンバと上部チャンバを満たす電解質溶液の特定イオンもしくはイオン群に対する濃度差を生じさせる必要がある。微小チャンバに充填する電解質溶液Ａと、上部チャンバに充填する電解質溶液Ｂのように、異なる種類の電解質溶液をFETのそれぞれのチャンバに供給する構成は、これを実現することができる。 In the FET of this embodiment, it is necessary to cause a concentration difference with respect to a specific ion or a group of ions in the electrolyte solution filling the microchamber and the upper chamber separated by the lipid bilayer membrane. A configuration in which different types of electrolyte solutions are supplied to the respective chambers of the FET, such as the electrolyte solution A filling the microchamber and the electrolyte solution B filling the upper chamber, can realize this.
　しかしながら、溶液充填後に脂質二重膜両側の二つの電解質溶液にイオン濃度差を生じさせることができるのであれば、微小チャンバと上部チャンバに充填する電解質溶液が同じ種類であってもよい。採用する脂質二重膜は、一般の生体細胞膜と同様に、イオンチャネルの機能を有することを想定している。したがって、例えば、充填後に上部チャンバの溶液へ特定イオンを補充する機構や、イオンチャネル自身に能動的な機能を付加できれば、脂質二重膜で隔てられた微小チャンバと上部チャンバの電解質溶液に濃度差を生じさせることができる。 However, the electrolyte solution to be filled in the microchamber and the upper chamber may be of the same type as long as a difference in ion concentration can be generated between the two electrolyte solutions on both sides of the lipid bilayer after filling the solution. It is assumed that the lipid bilayer to be employed has the function of an ion channel similarly to a general biological cell membrane. Therefore, for example, if a mechanism for replenishing specific ions to the solution in the upper chamber after filling or an active function can be added to the ion channel itself, there is a difference in concentration between the electrolyte solution in the microchamber and the upper chamber separated by the lipid bilayer membrane. Can be generated.
　本実施例によれば、補綴器官、ロボットの検知系へ応用可能な、嗅覚センサ、味覚センサに適用できる脂質二重膜を用いた生体模倣の分子検出センサ素子およびセンサデバイスを提供することができる。 According to the present embodiment, it is possible to provide a biomimetic molecular detection sensor element and sensor device using a lipid bilayer membrane applicable to a prosthetic organ and a robot detection system, and applicable to an olfactory sensor and a taste sensor. .
　また、本実施例に示すデバイス構造を採用することにより、以下の効果を得ることができる。 Further, by adopting the device structure shown in this embodiment, the following effects can be obtained.
　（１）FETのチャネルと脂質二重膜を同一の基板上に構成するため、従来のように基板貼合わせ、貼合わせのための尤度を確保する必要がない。そのため、デバイスサイズを縮小できる。また部品点数、工程数を削減でき、低コスト化が可能となる。 (1) Since the FET channel and the lipid bilayer membrane are formed on the same substrate, it is not necessary to secure the likelihood for substrate bonding and bonding as in the past. Therefore, the device size can be reduced. In addition, the number of parts and the number of processes can be reduced, and the cost can be reduced.
　（２）微小チャンバをFET作製工程と同様にリソグラフィー工程で形成することが可能となる。そのため、微小チャンバの密度、位置、形状を、自由に高精度に形成することが可能となり、その結果デバイスの検出感度向上が可能になる。 (2) A micro chamber can be formed by a lithography process in the same manner as the FET fabrication process. Therefore, the density, position, and shape of the micro chamber can be freely formed with high accuracy, and as a result, the detection sensitivity of the device can be improved.
　（３）デバイスのマイクロ流路に、電解質溶液、脂質溶液、界面活性剤を適宜投入することにより、微小チャンバ表面に脂質二重膜の平面膜を再現性良く形成することが可能になる。これにより、脂質二重膜の人工的な新陳代謝を実現することができ、デバイスの寿命を延ばすことが可能となる。 (3) By appropriately introducing an electrolyte solution, a lipid solution, and a surfactant into the microchannel of the device, it becomes possible to form a lipid bilayer membrane on the surface of the microchamber with good reproducibility. Thereby, artificial metabolism of the lipid bilayer membrane can be realized, and the life of the device can be extended.
　１：シリコン基板、２：ソース、３：ドレイン、４：FETチャネル、５：ゲート絶縁層、６：微小チャンバ、７：絶縁層、８：脂質二重膜、９：上部チャンバ、１０：シース、１１：参照電極、１２：マイクロ流路、１３：受容体 1: silicon substrate, 2: source, 3: drain, 4: FET channel, 5: gate insulating layer, 6: micro chamber, 7: insulating layer, 8: lipid bilayer, 9: upper chamber, 10: sheath, 11: Reference electrode, 12: Microchannel, 13: Receptor

Claims (12)

  1. 　絶縁基板上に形成された電界効果トランジスタ（FET）を備えるセンサ素子において、
    　前記FETに含まれるチャネルの上方に形成される第１のチャンバと、
    　前記第１のチャンバの上方に形成される第２のチャンバとを備え、
    　前記第１のチャンバと前記第２のチャンバは電解質溶液で満たされており、
    　前記第１のチャンバと前記第２のチャンバの境界に脂質二重膜が形成されることを特徴とするセンサ素子。     In a sensor element comprising a field effect transistor (FET) formed on an insulating substrate,
    A first chamber formed above a channel included in the FET;
    A second chamber formed above the first chamber,
    The first chamber and the second chamber are filled with an electrolyte solution;
    A sensor element, wherein a lipid bilayer is formed at a boundary between the first chamber and the second chamber.
  2. 　前記第１のチャンバは、前記第２のチャンバよりも容量が小さいことを特徴とする請求項１記載のセンサ素子。 The sensor element according to claim 1, wherein the first chamber has a smaller capacity than the second chamber.
  3. 　前記第１のチャンバは溝形状であり、前記溝形状の長軸方向は、前記FETチャネル内の電流方向と平行になるように溝が形成されることを特徴とする請求項１記載のセンサ素子。 2. The sensor element according to claim 1, wherein the first chamber has a groove shape, and a groove is formed so that a major axis direction of the groove shape is parallel to a current direction in the FET channel. .
  4. 　前記第１のチャンバは、前記FETチャネルの上方に複数形成されることを特徴とする請求項３記載のセンサ素子。 The sensor element according to claim 3, wherein a plurality of the first chambers are formed above the FET channel.
  5. 　前記第２のチャンバの下部に、複数のFETが形成され、かつ前記各FETと前記第２のチャンバとの間に、それぞれ第１のチャンバが形成されることを特徴とする請求項４記載のセンサ素子。 The plurality of FETs are formed in a lower portion of the second chamber, and a first chamber is formed between each FET and the second chamber, respectively. Sensor element.
  6. 　前記複数の第１のチャンバの体積が互いに異なることを特徴とする請求項４記載のセンサ素子。 5. The sensor element according to claim 4, wherein the plurality of first chambers have different volumes.
  7. 　前記センサ素子は、前記第１のチャンバを規定する絶縁層を備え、
    　前記絶縁層は、前記絶縁層の前記第二のチャンバ側に、前記絶縁基板側から親水性絶縁層、疎水性絶縁層、及び親水性絶縁層の順で積層された構造であることを特徴とする請求項１記載のセンサ素子。     The sensor element includes an insulating layer that defines the first chamber;
    The insulating layer has a structure in which a hydrophilic insulating layer, a hydrophobic insulating layer, and a hydrophilic insulating layer are stacked in this order from the insulating substrate side on the second chamber side of the insulating layer. The sensor element according to claim 1.
  8. 　前記センサ素子は、前記第１のチャンバを規定する絶縁層を備え、
    　前記絶縁層は、前記絶縁基板側の密度が、前記第２のチャンバ側の密度に比べ高いことを特徴とする請求項１記載のセンサ素子。     The sensor element includes an insulating layer that defines the first chamber;
    The sensor element according to claim 1, wherein the insulating layer has a higher density on the insulating substrate side than on the second chamber side.
  9. 　前記センサ素子は、前記第１のチャンバを規定する絶縁層を備え、
    　前記絶縁層は、前記絶縁基板側から、シリコン酸化膜、シリコン窒化膜、シリコン酸化膜の順番で積層された多層構造になっており、
    　前記絶縁基板側のシリコン酸化膜の密度が、前記第２のチャンバ側のシリコン酸化膜の密度に比べ高いことを特徴とする請求項１記載のセンサ素子。     The sensor element includes an insulating layer that defines the first chamber;
    The insulating layer has a multilayer structure in which a silicon oxide film, a silicon nitride film, and a silicon oxide film are stacked in this order from the insulating substrate side.
    2. The sensor element according to claim 1, wherein the density of the silicon oxide film on the insulating substrate side is higher than the density of the silicon oxide film on the second chamber side.
  10. 　前記センサ素子のFETは、ソースおよびドレインを含み、
    　前記FETのチャネル、ソースおよびドレインは、SOI基板に形成されることを特徴とする請求項１に記載のセンサ素子。     The FET of the sensor element includes a source and a drain,
    The sensor element according to claim 1, wherein a channel, a source, and a drain of the FET are formed on an SOI substrate.
  11. 　請求項１に記載したセンサ素子と、
    　前記第一のチャンバに充填する電解質溶液を供給する第１の供給部と、
    　前記第二のチャンバに充填する電解質溶液を供給する第２の供給部と、
    　前記第一のチャンバおよび前記第二のチャンバの境界に形成される脂質二重膜を構成する成分を含む脂質溶液を前記センサ素子に供給する第３の供給部と、
    　前記脂質二重膜を分解する界面活性剤を前記センサ素子に供給する第４の供給部と、
    　前記センサ素子に供給された液体を排出する廃液部と、
    　前記各供給部および前記廃液部を制御する制御部とを備えることを特徴とするセンサデバイス。     A sensor element according to claim 1;
    A first supply unit for supplying an electrolyte solution filling the first chamber;
    A second supply part for supplying an electrolyte solution for filling the second chamber;
    A third supply unit for supplying a lipid solution containing a component constituting a lipid bilayer formed at a boundary between the first chamber and the second chamber to the sensor element;
    A fourth supply unit that supplies the sensor element with a surfactant that decomposes the lipid bilayer;
    A waste liquid part for discharging the liquid supplied to the sensor element;
    A sensor device comprising: a controller that controls each of the supply units and the waste liquid unit.
  12. 　前記センサデバイスは、前記センサ素子を複数備え、
    　前記複数のセンサ素子は、前記各供給部および廃液部と、選択バルブを介して接続されることを特徴とする請求項１１記載のセンサデバイス。     The sensor device includes a plurality of the sensor elements,
    The sensor device according to claim 11, wherein the plurality of sensor elements are connected to each of the supply unit and the waste liquid unit via a selection valve.
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