WO2010107122A1 - 中空マイクロチューブ構造体およびその作製方法ならびに生体検査装置 - Google Patents
中空マイクロチューブ構造体およびその作製方法ならびに生体検査装置 Download PDFInfo
- Publication number
- WO2010107122A1 WO2010107122A1 PCT/JP2010/054893 JP2010054893W WO2010107122A1 WO 2010107122 A1 WO2010107122 A1 WO 2010107122A1 JP 2010054893 W JP2010054893 W JP 2010054893W WO 2010107122 A1 WO2010107122 A1 WO 2010107122A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- hollow
- coating layer
- hollow tube
- substrate
- semiconductor substrate
- Prior art date
Links
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/24—Detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B10/00—Other methods or instruments for diagnosis, e.g. instruments for taking a cell sample, for biopsy, for vaccination diagnosis; Sex determination; Ovulation-period determination; Throat striking implements
- A61B10/02—Instruments for taking cell samples or for biopsy
- A61B10/0233—Pointed or sharp biopsy instruments
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
- A61B5/0082—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence adapted for particular medical purposes
- A61B5/0084—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence adapted for particular medical purposes for introduction into the body, e.g. by catheters
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B81—MICROSTRUCTURAL TECHNOLOGY
- B81C—PROCESSES OR APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OR TREATMENT OF MICROSTRUCTURAL DEVICES OR SYSTEMS
- B81C1/00—Manufacture or treatment of devices or systems in or on a substrate
- B81C1/00015—Manufacture or treatment of devices or systems in or on a substrate for manufacturing microsystems
- B81C1/00023—Manufacture or treatment of devices or systems in or on a substrate for manufacturing microsystems without movable or flexible elements
- B81C1/00111—Tips, pillars, i.e. raised structures
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B2562/00—Details of sensors; Constructional details of sensor housings or probes; Accessories for sensors
- A61B2562/02—Details of sensors specially adapted for in-vivo measurements
- A61B2562/028—Microscale sensors, e.g. electromechanical sensors [MEMS]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/0002—Remote monitoring of patients using telemetry, e.g. transmission of vital signals via a communication network
- A61B5/0015—Remote monitoring of patients using telemetry, e.g. transmission of vital signals via a communication network characterised by features of the telemetry system
- A61B5/0017—Remote monitoring of patients using telemetry, e.g. transmission of vital signals via a communication network characterised by features of the telemetry system transmitting optical signals
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B81—MICROSTRUCTURAL TECHNOLOGY
- B81B—MICROSTRUCTURAL DEVICES OR SYSTEMS, e.g. MICROMECHANICAL DEVICES
- B81B2201/00—Specific applications of microelectromechanical systems
- B81B2201/05—Microfluidics
- B81B2201/055—Microneedles
-
- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01L—SEMICONDUCTOR DEVICES NOT COVERED BY CLASS H10
- H01L2924/00—Indexing scheme for arrangements or methods for connecting or disconnecting semiconductor or solid-state bodies as covered by H01L24/00
- H01L2924/0001—Technical content checked by a classifier
- H01L2924/0002—Not covered by any one of groups H01L24/00, H01L24/00 and H01L2224/00
Definitions
- the present invention relates to a hollow microtube structure, a manufacturing method thereof, and a biological examination apparatus.
- Non-Patent Documents 1 and 2 a technique related to creating a chemical solution transport device or a signal measurement device using a technique for manufacturing MEMS is described in literatures (Non-Patent Documents 1 and 2). Further, a technique related to a technique in which a chemical solution transport tube structure and a signal measurement probe electrode are formed on the same substrate is described in a document (Non-patent Document 3).
- micro probe electrodes and hollow tubes are required from the viewpoint of minimal invasiveness, and neuropotential measurement and pharmacological delivery are performed using these. Is expected.
- local nerve cell analysis requires that electrical measurement, chemical measurement, optical measurement, and the like can be performed simultaneously at the same location.
- the probe electrode and the hollow tube are separately manufactured, it is difficult for the electrode and the tube to simultaneously contact or invade a local region (for example, a region having a cell as a unit). Or there was a problem that the optical stimulus and the response to these could not be measured sufficiently. And even if both can be formed on the same substrate, it is not possible to configure the remaining of the silicon crystal forming the probe electrode and the removal of the crystal for forming the tube structure at a close distance. As a result, they are manufactured apart from each other. As described above, even in the structure in which the probe electrode and the tube are formed at the distant positions, there is a problem that it is difficult to simultaneously contact or invade the local region with the electrode and the tube.
- the diameter of the electrode tip is required to be several ⁇ m.
- this reduces the surface area of the electrode tip, so that electrical Impedance increased. For this reason, signal attenuation is caused in the probe electrode, and there is a problem that when measuring a minute cell signal, the nerve potential is attenuated and measurement becomes difficult.
- the tube is used to give a stimulus by infusion or suction of a chemical solution or the like, and an electrode different from the tube is used to measure the response to the stimulus. Therefore, the numbers of tubes and electrodes differ depending on the matters to be measured. Therefore, a large number of electrodes and tubes had to be prepared in order to cope with all measurement conditions.
- the present invention provides a hollow microtube structure that can be used as a minimally invasive electrode and a method for manufacturing the same, in order to enable measurement of a response by electrical, chemical, or optical stimulation in a local region at the same time.
- An object of the present invention is to provide a living body inspection apparatus using the hollow microtube structure.
- the present invention has been devised in order to achieve the above object, and the invention relating to a hollow microtube structure includes a semiconductor substrate and a hollow portion linearly orthogonal to the surface of the semiconductor substrate. At least one hollow tube provided on the surface in the form of a microscale tube, a metal coating layer constituting the inner surface of the hollow tube, and an outer surface of the hollow tube.
- the gist of the present invention is a hollow microtube structure comprising: an insulating coating layer to be formed; and a through hole that opens on the back surface of the semiconductor substrate while communicating with an extension of a hollow portion of the hollow tube.
- the metal coating layer is disposed on the inner surface of the hollow tube, it functions as an electrode by filling the hollow inside of the hollow tube with, for example, physiological saline. Further, since the periphery of the metal coating layer is surrounded by the insulating coating layer, at least the metal coating layer excluding the edge of the tip portion is totally insulated, and an electrical signal is transmitted to the metal coating layer. At the time of transmission, electrical conduction with the periphery of the hollow tube is cut off, and electrical stimulation at unnecessary portions can be eliminated.
- the semiconductor substrate is a silicon substrate
- the hollow tube has a two-layer structure formed by laminating a metal coating layer and an insulating coating layer, continuous to each layer constituting the hollow tube, and the metal coating layer and It is good also as a structure which laminates
- the conductive portion connected to the metal film in the hollow tube can be formed on the surface while the hollow tube having the above-described action is provided on the surface of the silicon substrate. Thereby, it is possible to transmit a change in potential in the living body. Further, by forming a semiconductor integrated circuit on the substrate, it is possible to configure a semiconductor chip that measures and analyzes the potential change.
- each said invention can be set as the structure by which the said hollow tube was formed in the array form on the surface of the said board
- nanoscale micro hollow tubes can be formed close to each other on the same substrate, and electrical stimulation, chemical stimulation, and / or optical stimulation is applied to, for example, cell fibers.
- electrical stimulation, chemical stimulation, and / or optical stimulation is applied to, for example, cell fibers.
- the present invention according to the method for producing the hollow microtube structure includes an erosion process of eroding both the front and back surfaces of a semiconductor substrate, and a pseudo-regulation for forming a column body in a range eroded on the surface side of the semiconductor substrate.
- the gist of this is a method for producing a hollow microtube structure.
- the erosion step includes a step of forming a film on both front and back surfaces of the semiconductor substrate, a step of removing a part of the film, and a step of eroding the semiconductor substrate in a range where the film is removed.
- the perforating step may be a perforating step in which the semiconductor substrate is perforated until the pillar body is removed and the semiconductor substrate reaches an eroded region.
- the film is removed only at an appropriate place on the back side of the substrate, and only a desired position can be eroded, and the hollow tube formed on the front side and the back side are formed.
- the position of the erosion part (perforation) to be provided can be provided on a linear extension line.
- the range in which the substrate is eroded from the back side of the substrate is formed in a wider range than the space formed in the hollow tube in order to ensure the perforation in the perforation process.
- a space is appropriately formed on the back surface side, so that it can function as a liquid reservoir when a chemical solution or the like is injected, and connectors for various devices can be provided.
- the metal coating layer forming step forms a metal coating layer on the substrate surface at the same time as forming the metal coating layer around the pillar
- the insulating coating layer forming step includes the metal coating layer forming step.
- An insulating coating layer is formed around the coating layer, and at the same time, an insulating coating layer is formed on the metal coating layer on the substrate surface.
- the present invention relating to a biopsy device using a hollow microtube structure is a biopsy device using the hollow microtube structure according to any one of claims 1 to 3, wherein the hollow microtube A chemical liquid injection means for supplying a chemical liquid into the hollow interior of the hollow tube, and an electrical signal transmitting means for conducting to the hollow tube, provided continuously to the structure, an opening opening on the substrate rear surface side of the through hole, and
- the gist of the present invention is a living body inspection apparatus including an electrical measuring unit.
- a drug solution is injected into a nerve cell, and the reaction of the nerve cell is measured by an electrical measurement means that conducts to another hollow tube.
- an electrical signal is transmitted from the electrical signal transmitting means to the nerve cells, for example, and nerve cells are electrically stimulated. It is also possible to measure.
- the internal space of the hollow tube is filled with physiological saline, for example, by injecting physiological saline into the hollow tube through which the electrical signal transmitting means and electrical measuring means are conducted. Therefore, transmission / reception can be performed while reducing the attenuation rate of the electrical signal.
- physiological saline for example, by injecting physiological saline into the hollow tube through which the electrical signal transmitting means and electrical measuring means are conducted. Therefore, transmission / reception can be performed while reducing the attenuation rate of the electrical signal.
- a hollow microtube structure in which hollow tubes are formed in an array is used, a plurality of hollow tubes can be formed at very close positions.
- the reaction can be electrically measured, for example, as a change in potential.
- this invention concerning a biopsy apparatus is a biopsy apparatus which uses the hollow microtube structure in any one of Claim 1 thru
- the gist of the present invention is also a biopsy device characterized by comprising an optical measuring means.
- a single hollow tube is used to irradiate light inside the living body (for example, nerve cells), and the other hollow tube is used to receive light reflected inside the living body. Therefore, it is possible to perform an optical analysis using the reflected light of a part of the living body. In addition to performing an inspection to measure the optical response of the reflected light to an optical stimulus caused by light irradiation, it is also possible to perform an inspection to check the color of the cell and its surroundings with the reflected light. it can.
- the medical solution is further provided continuously through an opening portion that opens on the back side of the substrate of the through hole, and supplies the chemical solution through the hollow tube. It can be set as the structure provided with the chemical
- the biopsy device according to any one of claims 7 to 10 is further provided continuously to an opening portion that opens to the back side of the substrate of the through hole, and passes through the inside of the hollow tube.
- the liquid extraction means for sucking and extracting the chemical liquid or the body fluid and the chemical measurement means provided continuously or in the middle of the liquid extraction means can be provided.
- electrical stimulation stimulation given by the electrical signal transmission means
- chemical stimulation stimulation given by the chemical solution injection means
- optical stimulation optical signal transmission means
- Change in the body fluid around the nerve cell can be chemically measured, and when the once injected chemical solution is sucked, the change in the chemical solution can be measured chemically.
- the chemical analysis can be measured by using different reactants depending on the object (body fluid or various chemicals) to be suctioned and extracted by the liquid extraction means.
- the present invention relating to the hollow microtube structure, it is possible to give an electrical, chemical or optical stimulus in a local region, and to measure a response to these stimuli. It is also possible to perform these measurements at the same place at the same time. Furthermore, since a fine hollow tube can function as an electrode, it is possible to perform stimulation and measurement that contribute to minimally invasiveness.
- the measuring means for measuring the change is an electrical measuring means that can measure a change in potential, for example, and an optical measuring means can measure the wavelength of received light, for example.
- the measurement result can be the inspection result by specifically limiting the object of inspection by assuming that the presence or amount of a specific component etc. can be measured, for example It is.
- FIG. 1 shows a process from a prior process to a process of forming a column
- FIG. 2 shows a process from a process of forming a metal coating layer to a final process.
- a step of forming a columnar body (hereinafter referred to as a probe) 24 (a pseudo layer formation step) is performed.
- the probe 24 is formed on the surface side of the substrate 2 (that is, the side opposite to the erosion region).
- the film 28 formed on the surface of the substrate 2 in the preliminary process is partially removed, and a void is formed in the removed portion, and the metal film 22 is placed on the substrate surface in the void. (FIG. 1C).
- the gap is formed in a circular shape, and the position thereof is adjusted so as to be on the extended line of the erosion region on the back surface side of the substrate 2 formed in the preliminary process.
- the probe 24 standing from the substrate 2 is formed (FIG. 1D).
- a VLS crystal growth method is used for forming the probe 24, and the probe 8 is crystal-grown by supplying disilane (Si 2 H 6 ) gas or the like to the substrate 2 disposed in the high vacuum chamber.
- the height (length) of the probe 24 for crystal growth is adjusted by the gas supply time, and the diameter of the probe 24 is adjusted by the area of the metal film 22 or the like. This is the step of forming the column body.
- the metal coating layer 6 is formed, the surface of the gap is coated (in reality, the metal coating layer 6 It penetrates the entire gap portion).
- a deposition method or a sputtering method can be used.
- gold or platinum can be used, but iridium, silver or silver-silver chloride can be used.
- the metal coating layer 6 formed on the surface side of the substrate 2 is electrically insulated because the film 28 is interposed between the metal coating layer 6 and the substrate 2.
- a step of exposing the tip of the probe 24 is performed.
- the insulating film layer 8 constituting the outer layer, the metal film layer 6 constituting the inner layer, and the metal film 26 as a catalyst used in the VLS crystal growth method are removed (FIG. 2C).
- the removal method is not limited, and any method of wet etching or dry etching may be used.
- the insulating film layer 8 can be formed by a selective etching method or a RIE (Reactive Ion Etching) method, and the metal film layer 6 and the metal film 26 can be formed by RIE in addition to the method of dissolving with aqua regia. Can be by law.
- the metal coating layer 6 is etched slightly more than the insulating coating layer 8, so that the tip portion at the completion of the hollow tube after the final process protrudes the insulating coating layer 8 beyond the metal coating layer 6. Can be configured.
- a step of removing the probe 24 and perforating the substrate 2 is performed.
- the inside of the metal coating layer 6 is hollowed to form a hollow tube, and the internal space of the hollow tube is communicated with the back surface of the substrate 2 (FIG. 2 ( d)).
- xenon difluoride XeF 2
- iodine fluoride SF 6
- the etching rate of xenon difluoride is hardly scraped off.
- gallium arsenide is used for the probe 24, chlorine-based boron trichloride (BCl 3 ) can be used as an etching gas. This is the same for the etching of the substrate 2 (including the previous step).
- FIG. 3 is a schematic view of a hollow microtube structure formed by the above-described production method using a silicon substrate.
- the hollow interior of the hollow tube 4 communicates with the back surface side of the substrate 2 through the erosion region of the substrate 2, and the hollow tube 4 on the front surface side isolated from the back surface side by the presence of the main body portion of the substrate 2.
- the internal space is continuous with the space on the back surface side of the substrate 2.
- a metal coating layer 6 configured as an inner layer of the hollow tube 4 is formed up to the vicinity of the erosion region of the substrate 2, and electrical connection with the hollow tube 4 is possible also on the back surface side of the substrate 2.
- the hollow tube 4 function as a high-performance electrode with a minute diameter by filling the hollow tube 4 with physiological saline.
- the meaning of filling the hollow tube with physiological saline means that the entire hollow tube is in a conductive state, and the physiological saline is interposed including the entire range up to the electrical measuring means.
- the electrical measuring means and the tip of the hollow tube can be brought into conduction.
- the impedance can be reduced (about 1/10 times) by the resistance value of physiological saline (14.7 ⁇ cm). That is, it is possible to obtain an electrode that does not attenuate the signal even when measuring the nerve potential. Therefore, for example, a change in potential when a stimulus is applied to a nerve cell can be measured.
- the potential measurement signal at this time can be acquired from the metal film on the front surface side of the substrate 1 as well as from the back surface side.
- each of the hollow tubes 4 is inserted into the living body at the same time and the tip portion is disposed in the same local region, optical, chemical and electrical stimulations are applied sequentially or simultaneously, and the reaction at that time is performed. It can be measured sequentially.
- one hollow tube 4 is used as an electrode for potential measurement and the other three are used as hollow bodies that irradiate light sources having different wavelengths (for example, 470 nm, 525 nm, and 595 nm), the colors are different.
- the response to light (red, blue, green) stimuli can be measured. This is effective, for example, when examining a color reaction in nerve cells constituting the retina.
- a connector 34 connected to the flow path opening of the resin 38 with a microchannel is provided, and the syringe (syringe) 14 can be connected via the flexible tube 20.
- the light source can be arranged in the opening portion of the microhole formed linearly in the resin 38 with a microchannel. Note that by using a light emitting diode or a laser diode as the light source, it is possible to easily manage the timing of irradiation and the irradiation time.
- an electrical signal transmitting means (electrical signal transmitter), an optical signal transmitting means (optical signal transmitter), a chemical liquid injection means (chemical liquid injector), an electric It is possible to arrange a functional measuring means (electrical measuring instrument), an optical measuring means (optical measuring instrument) and a chemical measuring means (chemical measuring instrument) and to make them function. Furthermore, when a syringe is used as the chemical solution injection means (chemical solution injector), it can function as a liquid extraction means (liquid extractor) for sucking and extracting the chemical solution or body fluid.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Surgery (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Medical Informatics (AREA)
- Molecular Biology (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pathology (AREA)
- Physics & Mathematics (AREA)
- Biophysics (AREA)
- Manufacturing & Machinery (AREA)
- Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- Microelectronics & Electronic Packaging (AREA)
- Micromachines (AREA)
- Measurement And Recording Of Electrical Phenomena And Electrical Characteristics Of The Living Body (AREA)
Abstract
Description
ことが要求されるものの、これでは電極先端の表面積が小さくなり、生体溶液中での電気的なインピーダンスが大きくなるものであった。そのため、プローブ電極内において信号の減衰を招来し、微差な細胞信号を測定する際には、神経電位が減衰して測定が困難となるという問題があった。
位の電位の変化を計測することが可能となる。
導通させることにより、電気信号の減衰を低減させることができる。
れる。すなわち、基板2の表面側全体に形成された膜28の一部を除去して円形の空隙部が形成されたが、プローブ24は、その空隙部よりも小さな径で形成されることから、膜28とプローブ24の間には、空隙部の一部が間隙を構成することとなり、金属被膜層6を形成する際に、この間隙の表面が被膜される(現実的には金属被膜層6が間隙部分全体に侵入する)のである。ここで、上記の金属被膜層6を形成するためには、堆積法またはスパッタ法を用いることができる。また、使用される金属としては、金または白金を用いることができるが、イリジウム、銀または銀-塩化銀を使用することができる。特に、中空マクロチューブ構造体を細胞計測に使用する場合には、列記の材料による金属被膜層6を形成することが望ましい。なお、基板2の表面側に構成された金属被膜層6は、基板2との間に膜28が介在することとなり、電気的に絶縁された状態である。また、基板2の表面側にこのような金属被膜層6を部分的に形成しない場合には、当該基板2の表面に形成された金属被膜をエッチングにより除去される。
チューブ構造体の実施の形態について説明する。図3は、シリコン基板を使用して上記作成方法により構成した中空マイクロチューブ構造体の概略図である。
的計測手段(化学的計測器)を配置し、これらを機能させることができる。さらに、薬液注入手段(薬液注入器)としてシリンジを使用する場合には、薬液もしくは体液の吸引抽出する液体抽出手段(液体抽出器)として機能させることができる。
〔実験例1〕
まず、上記実施形態により作製した中空チューブ電極による電位計測時における信号の出力-入力比評価を行った。実験装置を図5に示す。このときの中空チューブ内には生理食塩水を充満させており、シリンジのシリンダ内に金のワイヤによって電極を設け、パルス発生器によって発生させた1kHzの正弦波(100mVp-p)の電気信号を抵抗減衰器により約1/1250まで減衰させ(減衰後は約80μVp-p)、これを中空チューブ先端付近に与えて実験した。その結果は図6のとおりとなった。また、図6には、参考のために径の異なる同種の中空チューブにおける実験結果を示している。従来から使用されるプローブ電極の実験結果を比較例として示している。この実験結果によれば、従来のプローブ電極では、直径を小さくすると出力-入力比が極端に減少するが、本実施例による中空チューブ電極では、外径を小さくしてもほとんど変化がないことが判明した。
〔実験例2〕
次に、溶液の吐出・吸引の可能性を実験した。実験装置は、図8に示すように、シリンジポンプ(Harvard社製Model11PicoPlus)によってプラスチックシリンジに圧力を加え、微小流量をセンシング可能なフローセンサ(Senssirion社製SLG1430)により流量を観測する構成とした。実験に使用した中空チューブは、内径が2.5μm、4.1μm、4.6μmおよび6.4μmで、いずれも長さを22μmとした4種類のものを使用した。その結果、いずれの中空チューブにおいても溶液の吐出が可能であった。そこで、さらに、内径2μmの中空チューブについての吐出・吸引の可能性を実験した。そのときの状態を図9に示す。図9は、中空チューブの先端側から撮影した写真である。この図において明らかなとおり、液体の吐出においても吸引においても、中空チューブを使用して可能であることが判明した。
〔実験例3〕
また、光の透過性について、基板2の裏面側から発光ダイオードを用いて光を照射し、中空チューブ先端に到達する光の状態を実験した。使用した中空チューブの内径は2μmであり、透過させる光は、波長470nm(青)、525nm(緑)および595nm(赤)に分けて行った。その結果を図10に示す。この実験結果により、いずれの波長の光についても中空チューブを透過することが確認された。
〔実験例4〕
さらに、神経細胞のように微小なターゲットを中空チューブの先端に固定できるか否か
について、マイクロビーズを用いて実験したところ、図11に示すように、マイクロビーズを完全に固定化していることを確認した。これにより、神経細胞のような微小なターゲットを固定化することが可能となった。なお、実験に使用する中空マイクロチューブ構造体の中空チューブが、金属被膜層の先端よりも絶縁被膜層の先端を突出させた構成のものであるとき、マイクロビーズと金属被膜層とのシール抵抗を測定したところ、数ギガオームであった。これは、マイクロビーズが金属被膜層に接していないことを示すものである。
4 中空チューブ
6 金属被膜層
8 絶縁被膜層
10 発光素子
12 薬液
14 注射器
16 アンプ・フィルター
18 光
20 フレキシブルチューブ
22 金属膜
24 プローブ
26 金属合金膜
28 膜
30 金属線
32 生理食塩水
34 コネクタ
36 テスト用マイクロビーズ
38 マイクロチャンネル付き樹脂
Claims (11)
- 半導体基板と、
該半導体基板の表面に対して直交方向に直線状に中空部を形成してなり、かつ、マイクロスケールの筒状に該表面上に設けられた少なくとも1つの中空チューブと、
該中空チューブの内部表面を構成する金属被膜層と、
前記中空チューブの外部表面を構成する絶縁被膜層と、
前記中空チューブの中空部の延長上に連通しつつ前記半導体基板の裏面で開口する貫通孔と、
を備えたことを特徴とする中空マイクロチューブ構造体。 - 前記半導体基板がシリコン基板であり、前記中空チューブが金属被膜層と絶縁被膜層を積層してなる二層構造の中空チューブであり、該中空チューブを構成する各層に連続し、かつ、金属被膜層および絶縁被膜層による積層体を該絶縁被膜層が外側に配置されつつ前記シリコン基板表面に積層してなることを特徴とする請求項1記載の中空マイクロチューブ構造体。
- 前記中空チューブが前記基板の表面にアレイ状に形成されたことを特徴とする請求項1または2に記載の中空マイクロチューブ構造体。
- 半導体基板の表裏両面を浸食する浸食工程と、
前記半導体基板の表面側で浸食された範囲に柱体を形成する擬制層形成工程と、
前記柱体の周囲に金属被膜層を形成する金属被膜層形成工程と、
前記柱体とは異なる材料の絶縁被膜層を前記金属被膜層の周囲に形成する絶縁被膜層形成工程と、
前記柱体の先端における絶縁被膜層および金属被膜層を除去し、前記柱体の先端部を露出させる先端除去工程と、
前記柱体を除去するとともに半導体基板を穿孔する穿孔工程と、
からなることを特徴とする中空マイクロチューブ構造体の作製方法。 - 前記浸食工程は、半導体基板の表裏両面に膜を形成する工程と、前記膜の一部を除去する工程と、膜を除去された範囲の前記半導体基板を浸食する工程とを含み、
前記穿孔工程は、前記柱体を除去するとともに、前記半導体基板が浸食された領域に到達するまで該半導体基板を穿孔する穿孔工程であることを特徴とする請求項4に記載の中空マイクロチューブ構造体の作製方法。 - 前記金属被膜層形成工程は、前記柱体の周囲に金属被膜層を形成すると同時に前記基板表面にも金属被膜層を形成し、前記絶縁被膜層形成工程は、前記金属被膜層の周囲に絶縁被膜層を形成すると同時に前記基板表面の金属被膜層に重ねて絶縁被膜層を形成することを特徴とする請求項4または5に記載の中空マイクロチューブ構造体の作成方法。
- 請求項1ないし3のいずれかに記載の中空マイクロチューブ構造体を使用する生体検査装置であって、
前記中空マイクロチューブ構造体と、
前記貫通孔の基板裏面側に開口する開口部に連続して設けられ、前記中空チューブの中空内部に薬液を供給する薬液注入手段と、
前記中空チューブに導通する電気信号発信手段および電気的計測手段と、
を備えたことを特徴とする生体検査装置。 - 請求項1ないし3のいずれかに記載の中空マイクロチューブ構造体を使用する生体検査装置であって、
前記中空マイクロチューブ構造体と、
前記貫通孔の基板裏面側に開口する開口部から前記中空チューブを透過する光源を発信する光学的信号発信手段と、
前記中空チューブの中空内部を経由して前記基板裏面側に到達する前記光源の反射光を受信する光学的計測手段と、
を備えたことを特徴とする生体検査装置。 - 請求項1ないし3のいずれかに記載の中空マイクロチューブ構造体を使用する生体検査装置であって、
前記中空マイクロチューブ構造体と、
前記貫通孔の基板裏面側に開口する開口部から前記中空チューブを透過する光源を発信する光学的信号発信手段と、
前記中空チューブに導通する電気的計測手段を備えたことを特徴とする生体検査装置。 - 請求項8または9に記載の生体検査装置であって、さらに、前記貫通孔の基板裏面側に開口する開口部に連続して設けられ、前記中空チューブ内部を経由して薬液を供給する薬液注入手段を備えたことを特徴とする生体検査装置。
- 請求項7ないし10のいずれか1項に記載の生体検査装置であって、さらに、前記貫通孔の基板裏面側に開口する開口部に連続して設けられ、前記中空チューブ内部を経由して体液または薬液を吸引抽出する液体抽出手段と、該液体抽出手段に連続しまたはその途中に設けられた化学的計測手段とを備えたことを特徴とする生体検査装置。
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US13/257,721 US20120016261A1 (en) | 2009-03-20 | 2010-03-19 | Hollow microtube structure, production method thereof and biopsy device |
JP2011504901A JP5429827B2 (ja) | 2009-03-20 | 2010-03-19 | 中空マイクロチューブ構造体およびその作製方法ならびに生体検査装置 |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2009-069216 | 2009-03-20 | ||
JP2009069216 | 2009-03-20 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2010107122A1 true WO2010107122A1 (ja) | 2010-09-23 |
Family
ID=42739778
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP2010/054893 WO2010107122A1 (ja) | 2009-03-20 | 2010-03-19 | 中空マイクロチューブ構造体およびその作製方法ならびに生体検査装置 |
Country Status (3)
Country | Link |
---|---|
US (1) | US20120016261A1 (ja) |
JP (1) | JP5429827B2 (ja) |
WO (1) | WO2010107122A1 (ja) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE102012006953A1 (de) * | 2012-04-04 | 2013-10-10 | Albert-Ludwigs-Universität Freiburg | Vorrichtung zur Stimulierung und/oder Detektion von Zellaktivitäten innerhalb einer Zellenumgebung |
JP6371439B1 (ja) * | 2017-04-28 | 2018-08-08 | 株式会社ライトショー・テクノロジー | 光源装置および投射型表示装置 |
JP7015679B2 (ja) | 2017-11-15 | 2022-02-03 | コニカミノルタ株式会社 | 撮像レンズ,撮像光学装置及びデジタル機器 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH03209103A (ja) * | 1990-01-11 | 1991-09-12 | Canon Inc | 微小プローブおよびその製造方法 |
JP2000197616A (ja) * | 1999-01-08 | 2000-07-18 | Hitachi Ltd | マイクロ電極の製造方法 |
JP2005337756A (ja) * | 2004-05-24 | 2005-12-08 | Toyohashi Univ Of Technology | マルチプローブ、これによって形成されるマルチセンサおよびマルチプローブの製造方法 |
-
2010
- 2010-03-19 JP JP2011504901A patent/JP5429827B2/ja active Active
- 2010-03-19 WO PCT/JP2010/054893 patent/WO2010107122A1/ja active Application Filing
- 2010-03-19 US US13/257,721 patent/US20120016261A1/en not_active Abandoned
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH03209103A (ja) * | 1990-01-11 | 1991-09-12 | Canon Inc | 微小プローブおよびその製造方法 |
JP2000197616A (ja) * | 1999-01-08 | 2000-07-18 | Hitachi Ltd | マイクロ電極の製造方法 |
JP2005337756A (ja) * | 2004-05-24 | 2005-12-08 | Toyohashi Univ Of Technology | マルチプローブ、これによって形成されるマルチセンサおよびマルチプローブの製造方法 |
Also Published As
Publication number | Publication date |
---|---|
JP5429827B2 (ja) | 2014-02-26 |
US20120016261A1 (en) | 2012-01-19 |
JPWO2010107122A1 (ja) | 2012-09-20 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Lee et al. | A multichannel neural probe with embedded microfluidic channels for simultaneous in vivo neural recording and drug delivery | |
JP6873303B2 (ja) | マイクロニードルおよびチップ | |
JP4353582B2 (ja) | 状態量を測定する方法および装置 | |
US9014796B2 (en) | Flexible polymer microelectrode with fluid delivery capability and methods for making same | |
Pongracz et al. | Deep-brain silicon multielectrodes for simultaneous in vivo neural recording and drug delivery | |
CN104271059B (zh) | 气泡喷出构件及其制造方法、气液喷出构件及其制造方法、局部消融装置及局部消融方法、注射装置及注射方法 | |
John et al. | Microfabrication of 3D neural probes with combined electrical and chemical interfaces | |
US8682412B2 (en) | Tetrode for measuring bio-signals and method of manufacturing the same | |
US20100241100A1 (en) | Real-time multimode neurobiophysiology probe | |
IE20050165A1 (en) | Apparatus for the prophylaxis or treatment of tissue | |
WO2011116388A1 (en) | Body fluid sampling/fluid delivery device | |
JP5429827B2 (ja) | 中空マイクロチューブ構造体およびその作製方法ならびに生体検査装置 | |
US20200261025A1 (en) | System and method for making and implanting high-density electrode arrays | |
EP2688485B1 (en) | Medical instruments and methods for fabricating same | |
Kim et al. | 3D silicon neural probe with integrated optical fibers for optogenetic modulation | |
US20120019270A1 (en) | Microfabricated pipette and method of manufacture | |
Frey et al. | Biosensor microprobes with integrated microfluidic channels for bi-directional neurochemical interaction | |
JP6869983B2 (ja) | モジュラー・デバイスおよびケーブル・アセンブリを含むプローブ・アセンブリおよびシステム | |
JP3893381B2 (ja) | 生体試料が発する電気信号を測定するための測定デバイスおよび測定方法 | |
JP4953357B2 (ja) | 細胞侵襲用プローブ及び該細胞侵襲用プローブを有する細胞侵襲装置、並びに、細部侵襲方法 | |
JP2008079608A (ja) | マイクロニードル搭載型バイオプローブ、およびマイクロニードル搭載型バイオプローブの作製方法 | |
EP3795064B1 (en) | Neural probe structure for measuring multiple fluorescence signals and manufacturing method thereof | |
Kim | Development of advanced multifunctional neural interface devices | |
Raghunathan | Design and Development of a Multiport Microfluidic Device for In Vitro Surface Stimulation of the Retina | |
JP2020524001A (ja) | ナノニードルならびに関連する装置および方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 10753613 Country of ref document: EP Kind code of ref document: A1 |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
WWE | Wipo information: entry into national phase |
Ref document number: 13257721 Country of ref document: US |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2011504901 Country of ref document: JP |
|
122 | Ep: pct application non-entry in european phase |
Ref document number: 10753613 Country of ref document: EP Kind code of ref document: A1 |