JP2005062137A - Apparatus for counting particulate in liquid - Google Patents

Apparatus for counting particulate in liquid Download PDF

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JP2005062137A
JP2005062137A JP2003296437A JP2003296437A JP2005062137A JP 2005062137 A JP2005062137 A JP 2005062137A JP 2003296437 A JP2003296437 A JP 2003296437A JP 2003296437 A JP2003296437 A JP 2003296437A JP 2005062137 A JP2005062137 A JP 2005062137A
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aperture
flow path
electrodes
liquid
blood
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JP3911259B2 (en
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Kazuhiro Miyamura
和宏 宮村
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Horiba Ltd
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume, or surface-area of porous materials
    • G01N15/10—Investigating individual particles
    • G01N15/1031—Investigating individual particles by measuring electrical or magnetic effects thereof, e.g. conductivity or capacity
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Abstract

<P>PROBLEM TO BE SOLVED: To provide an apparatus for counting particulates in a liquid which accurately counts the number of the desired particulates although bubbles are generated on an electrode. <P>SOLUTION: An aperture 2c is formed in the middle of a flow path 2 in which a liquid sample S flows from upstream to downstream. Two electrodes 5, 6 are provided in the flow path 2b downstream from the aperture 2c. A liquid dividing part 3 is provided in the vicinity of the aperture 2c in the downstream flow path 2b, and divides the liquid sample S flowing from the flow path 2a upstream from the aperture 2c through the aperture 2c in two direction to the electrodes. An impedance change generated when the liquid sample S passes through the aperture 2c is detected by the electrodes 5, 6. The number of the particulates contained in the liquid sample S is counted based on a detected result. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

この発明は、例えば、血液中の血球を計数する血球計数装置などの液体中の微粒子計数装置に関する。   The present invention relates to a fine particle counting device in a liquid such as a blood cell counting device for counting blood cells in blood.

従来から、血液中の赤血球、白血球、血小板などの血球を計数する手法の一つとして電気抵抗法が知られている。この電気抵抗法は、血液細胞を等張性希釈液に懸濁させ、粒子がアパーチャを通過するときに、血球が占める容積に比例した電気抵抗（インピーダンス）の変化が生じる。このインピーダンス変化に対応して生ずるパルス数を計数することにより、血球の個数を検出することができ、また、前記パルスの高さを検出することにより、血球の容積（白血球、赤血球、血小板であるかの種類）を検出することができる。   Conventionally, an electrical resistance method is known as one of methods for counting blood cells such as red blood cells, white blood cells, and platelets in blood. In this electrical resistance method, blood cells are suspended in an isotonic diluent, and when the particles pass through the aperture, a change in electrical resistance (impedance) proportional to the volume occupied by the blood cells occurs. By counting the number of pulses generated corresponding to this impedance change, the number of blood cells can be detected, and by detecting the height of the pulse, the volume of blood cells (white blood cells, red blood cells, platelets). Can be detected.

ところで、近年においては、血球計数装置のマイクロ化が進められており、前記電気抵抗法に則ったチップ状のマイクロ血球計数装置が開発されるに至っており、例えば、特許文献１に示すようなものが実用化されつつある。このマイクロ血球計数装置の測定部では、シリコン基板に測定対象である検体血液が流れる流入側の流路および流出側の流路と、これら流路の途中に狭隘部が形成されることにより得られるアパーチャと、このアパーチャの両側の流路に設けられる電極とが備えられている。   By the way, in recent years, the microcytometer of a blood cell counter has been promoted, and a chip-like micro blood cell counter conforming to the electric resistance method has been developed. For example, as shown in Patent Document 1 Is being put into practical use. The measurement unit of this micro blood cell counter is obtained by forming a flow path on the inflow side and a flow path on the outflow side through which the sample blood to be measured flows on the silicon substrate, and a narrow portion in the middle of these flow paths. An aperture and electrodes provided in flow paths on both sides of the aperture are provided.

図４は、この種の従来のマイクロ血球計数装置における測定部の構成を概略的に示すもので、この図において、５１はシリコン基板で、例えば厚さが５００μｍ、長さが１０ｍｍ、幅が５ｍｍ程度の大きさに形成されている。５２はシリコン基板５１の上面に、例えば、ＭＥＭＳ（マイクロ・エレクトロ・メカニカル・システムズ）プロセスなどによる加工技術を用いて形成される適宜の深さの流路である。   FIG. 4 schematically shows a configuration of a measuring unit in this type of conventional micro blood cell counter. In this figure, 51 is a silicon substrate, for example, having a thickness of 500 μm, a length of 10 mm, and a width of 5 mm. It is formed to a size of about. Reference numeral 52 denotes a flow path having an appropriate depth formed on the upper surface of the silicon substrate 51 using a processing technique such as a MEMS (Micro Electro Mechanical Systems) process.

前記流路５２は、そのほぼ中間において形成されて流路幅が狭くなった狭隘部としての５ｃと、この狭隘部５２ｃの両側に形成されて流路幅が比較的幅広である、狭隘部５２ｃより上流側の流路５２ａおよび狭隘部５２ｃより下流側の流路５２ｂとからなる。なお、前記狭隘部５２ｃは、シリコン基板５１の上方から流路５２を覆うようにしてシリコン基板５１に密着するように設けられるガラス板などの蓋体（図示していない）の下面と共働してアパーチャを構成する。以下、狭隘部５２ｃをアパーチャとも呼ぶ。   The flow path 52 is formed in a substantially middle portion of the narrow portion 5c as a narrow width portion and the narrow portion 52c formed on both sides of the narrow portion 52c and has a relatively wide flow width. It consists of a flow path 52a on the more upstream side and a flow path 52b on the downstream side of the narrow portion 52c. The narrow portion 52c cooperates with the lower surface of a lid (not shown) such as a glass plate provided so as to be in close contact with the silicon substrate 51 so as to cover the flow path 52 from above the silicon substrate 51. To configure the aperture. Hereinafter, the narrow portion 52c is also referred to as an aperture.

５３は上流側の流路５２ａの底部の表面に形成される電極であり、５４は下流側の流路５２ｂの底部の表面に形成される電極である。これらの電極５３，５４は、検出回路５５に接続されており、検体血液５６がアパーチャ５２ｃを通過するときに生ずるインピーダンス変化を検出するように構成されている。   53 is an electrode formed on the surface of the bottom of the upstream channel 52a, and 54 is an electrode formed on the surface of the bottom of the downstream channel 52b. These electrodes 53 and 54 are connected to a detection circuit 55 and configured to detect a change in impedance that occurs when the specimen blood 56 passes through the aperture 52c.

上記構成のマイクロ血球計数装置の測定部において、検体血液の測定を行う場合、適宜の希釈液で希釈された検体血液５６がサンプル導入口（図示していない）から上流側の流路５２ａに導入される。そして、この検体血液５６が上流側の流路５２ａからアパーチャ５２ｃを通過して下流側の流路５２ｂに導かれ、サンプル流出口（図示していない）から排出される。   When the sample blood is measured in the measurement unit of the micro blood cell counter having the above-described configuration, the sample blood 56 diluted with an appropriate diluent is introduced from the sample introduction port (not shown) into the upstream channel 52a. Is done. The sample blood 56 passes through the aperture 52c from the upstream flow path 52a, is guided to the downstream flow path 52b, and is discharged from the sample outlet (not shown).

ここで、検体血液５６がアパーチャ５２ｃを通過するとき、電極５３，５４間のインピーダンスが変化し、このインピーダンスの変化を示す検出信号が計器本体（図示していない）に入力され、計器本体において所定の演算が行われることによって、赤血球、白血球、血小板などの血球５７が計数される。
特開２０００−２７７３８０号公報 Here, when the sample blood 56 passes through the aperture 52c, the impedance between the electrodes 53 and 54 changes, and a detection signal indicating the change in the impedance is input to the instrument body (not shown), and the instrument body has a predetermined signal. By performing this calculation, blood cells 57 such as red blood cells, white blood cells, and platelets are counted.
JP 2000-277380 A

ところで、従来の液体中のマイクロ血球計数装置においては、その測定部において、アパーチャ５２ｃの上、下流側の流路５２ａ，５２ｂにそれぞれ電極５３，５４が設けられていたので、次のような不都合が生ずることがあった。すなわち、測定時には、前記電極５３，５４に所定の電圧が印加され、これらを含む回路には所定の電流がながれている。このため、検体血液５６が特に、上流側に位置する電極５３に接触したとき、前記電流によって検体血液５６が電気分解され、これによって、電極５３において泡５８が発生する。この泡５８が検体血液５６とともにアパーチャ５２ｃを通過すると、電極５３，５４間のインピーダンスが変化し、これを血球と同様に検出する。つまり、前記電気分解によって生じた泡５８がノイズとなり、検出信号の精度が低下し、これに伴って、検体血液の血球の計数精度が低下することになる。   By the way, in the conventional micro blood cell counter in liquid, the electrodes 53 and 54 are provided in the flow paths 52a and 52b on the downstream side of the aperture 52c in the measurement unit, respectively. Sometimes occurred. That is, at the time of measurement, a predetermined voltage is applied to the electrodes 53 and 54, and a predetermined current flows through a circuit including them. For this reason, particularly when the sample blood 56 comes into contact with the electrode 53 located on the upstream side, the sample blood 56 is electrolyzed by the current, thereby generating a bubble 58 at the electrode 53. When the bubble 58 passes through the aperture 52c together with the sample blood 56, the impedance between the electrodes 53 and 54 changes, and this is detected in the same manner as a blood cell. That is, the bubble 58 generated by the electrolysis becomes noise, and the accuracy of the detection signal is lowered, and accordingly, the counting accuracy of the blood cells of the sample blood is lowered.

これに対して、前記電極５３，５４に印加する電圧を低くして電気分解が起こらないようにすることが考えられるが、このようにすると、電極５３，５４間のインピーダンスの変化レベルが小さくなって、インピーダンス変化を示す検出信号の精度が低下し、この結果、検体血液の血球の計数精度が低下することになる。   On the other hand, it is conceivable that the voltage applied to the electrodes 53 and 54 is lowered so that electrolysis does not occur. However, in this case, the level of change in impedance between the electrodes 53 and 54 is reduced. As a result, the accuracy of the detection signal indicating the impedance change is lowered, and as a result, the counting accuracy of the blood cells of the sample blood is lowered.

なお、上述のような問題は、半導体製造工程における半導体ウェハの洗浄などに用いられる洗浄用液体中や超純水中に含まれる微粒子の計数を行う液体中の微粒子計数装置においても同様に生じているところである。   The above-mentioned problems also occur in the fine particle counting apparatus in the liquid that counts the fine particles contained in the cleaning liquid or ultrapure water used for cleaning the semiconductor wafer in the semiconductor manufacturing process. It is where you are.

この発明は、上述の事柄に留意してなされたもので、その目的は、電極において泡が発生するなどしても、所望の微粒子の数を高精度で計数することのできる液体中の微粒子計数装置を提供することである。 The present invention has been made in consideration of the above-described matters, and its purpose is to count fine particles in a liquid that can count the number of desired fine particles with high accuracy even if bubbles are generated in an electrode. Is to provide a device.

上記目的を達成するために、この発明の液体中の微粒子計数装置は、液体試料が上流側から下流側に向かって流れる流路の途中にアパーチャを形成し、このアパーチャより下流側の流路に２個の電極を設けるとともに、前記下流側の流路の前記アパーチャの近傍に、前記アパーチャより上流側の流路から当該アパーチャを経て流れてくる液体試料を前記２つの電極方向に分割する液分割部を設け、前記液体試料が前記アパーチャを通過するときに生ずるインピーダンス変化を前記両電極によって検出し、この検出結果に基づいて前記液体試料中に含まれる粒子数を計数するようにしたことを特徴としている。   In order to achieve the above object, the fine particle counting apparatus in the liquid according to the present invention forms an aperture in the middle of the flow path where the liquid sample flows from the upstream side toward the downstream side, and the flow path is located downstream of the aperture. Liquid division that provides two electrodes and divides a liquid sample flowing from the flow path upstream of the aperture via the aperture in the vicinity of the aperture of the downstream flow path in the direction of the two electrodes And an impedance change that occurs when the liquid sample passes through the aperture is detected by the two electrodes, and the number of particles contained in the liquid sample is counted based on the detection result. It is said.

上記構成よりなる液体中の微粒子計数装置においては、アパーチャの下流側の流路に液体試料が前記アパーチャを通過するときに生ずるインーダンス変化を検出するための電極を設けているので、仮に電極において泡が生じても、この泡がアパーチャを通過することがない。したがって、従来のこの種の装置と異なり、泡によるノイズが発生することがなくなり、ノイズが低減される。そして、電極間に印加する電圧を大きくすることができるので、より大きな検出信号が得られ、検出精度の高い測定を行うことができる。 In the fine particle counting apparatus having the above-described configuration, an electrode for detecting an impedance change that occurs when a liquid sample passes through the aperture is provided in the flow path on the downstream side of the aperture. If this occurs, the bubbles will not pass through the aperture. Therefore, unlike this type of conventional device, noise due to bubbles is not generated, and the noise is reduced. Since the voltage applied between the electrodes can be increased, a larger detection signal can be obtained and measurement with high detection accuracy can be performed.

図１および図２は、この発明の第１実施例を示す。そして、図１は、この発明の液体中の微粒子計数装置としてのマイクロ血球計数装置の測定部におけるチップ構成を示す斜視図であり、図２は、前記測定部の要部を拡大して示す平面図である。   1 and 2 show a first embodiment of the present invention. FIG. 1 is a perspective view showing a chip configuration in a measuring unit of a micro blood cell counter as a microparticle counter in a liquid according to the present invention, and FIG. 2 is an enlarged plan view showing a main part of the measuring unit. FIG.

前記図１および図２において、１はシリコン基板で、例えば厚さが５００μｍ、長さが１０ｍｍ、幅が５ｍｍ程度の大きさに形成されている。２はシリコン基板１の上面に、例えばＭＥＭＳプロセスなどによる加工技術を用いて形成される適宜の深さの流路である。この流路２は、そのほぼ中間において形成され流路幅が狭くなった狭隘部２ｃと、この狭隘部２ｃの両側に形成され流路幅が比較的幅広である流路２ａ，流路２ｂとからなる。今、説明の便宜上、一方の流路２ａを上流側流路２ａ、他方の流路２ｂを下流側流路２ｂという．なお、狭隘部２ｃは、後述するガラス板の下面と共働してアパーチャを構成する。以下、狭隘部２ｃをアパーチャとも呼ぶ。そして、前記流路２ａ，流路２ｂの幅（図２中のＷ1 ，Ｗ2 ）は例えば３ｍｍである。また、アパーチャ２ｃの開口は５０μｍである。 In FIG. 1 and FIG. 2, reference numeral 1 denotes a silicon substrate, which has a thickness of about 500 μm, a length of 10 mm, and a width of about 5 mm. Reference numeral 2 denotes a flow path having an appropriate depth formed on the upper surface of the silicon substrate 1 by using a processing technique such as a MEMS process. The channel 2 includes a narrow portion 2c formed in the middle of the narrow channel 2c and a narrow channel, and channels 2a and 2b formed on both sides of the narrow unit 2c and having a relatively wide channel width. Consists of. For convenience of explanation, one channel 2a is referred to as an upstream channel 2a, and the other channel 2b is referred to as a downstream channel 2b. In addition, the narrow part 2c cooperates with the lower surface of the glass plate mentioned later, and comprises an aperture. Hereinafter, the narrow portion 2c is also referred to as an aperture. Then, (W 1, W 2 in FIG. 2) the flow channel 2a, the width of the flow path 2b is 3mm, for example. The opening of the aperture 2c is 50 μm.

３は下流側流路２ｂ内に設けられる液分割部で、上流側流路２ａからアパーチャ２ｃを経て下流側流路２ｂ内に流入してくる検体血液Ｓを２つの等しい流れに分岐するもので、蓋としてのガラス板１２（後述する）の下面と密着する高さを有するとともに、一旦分岐した検体血液Ｓが互いに混じらないように構成されている。この実施例においては、その上流側（アパーチャ２ｃに近い側）の先端部３ａの平面視形状が曲面（例えば半円形）に形成され、これに連なる部分２ｂが下流側流路２ｂ内を流れの方向において二分するように直線的に設けられている。そして、液分割部３の先端部３ａの対向する壁面４ａ，４ｂとの間に、二つの隙間ｄ1 ，ｄ2 が形成され、これらの隙間ｄ1 ，ｄ2 の開口がアパーチャ２ｃの開口径（この例では５０μｍ）とほぼ等しくなるように設定してある。なお、２ｂ1 ，２ｂ2 は、前記液分割部３によって互いに連通しないように区画された下流側流路２ｂ内の二つの部分である。 Reference numeral 3 denotes a liquid dividing section provided in the downstream flow path 2b, which branches the sample blood S flowing into the downstream flow path 2b from the upstream flow path 2a through the aperture 2c into two equal flows. It has a height that is in close contact with the lower surface of a glass plate 12 (described later) as a lid, and is configured so that the once-divided specimen blood S is not mixed with each other. In this embodiment, the shape of the front end portion 3a on the upstream side (side close to the aperture 2c) is formed in a curved surface (for example, a semicircular shape), and a portion 2b connected to the tip portion 3a flows in the downstream channel 2b. It is provided linearly so as to bisect in the direction. Then, two gaps d 1 and d 2 are formed between the opposing wall surfaces 4a and 4b of the tip 3a of the liquid dividing part 3, and the openings of these gaps d 1 and d 2 are the opening diameters of the aperture 2c. It is set to be substantially equal to (50 μm in this example). Reference numerals 2b 1 and 2b 2 denote two portions in the downstream flow path 2b that are partitioned by the liquid dividing section 3 so as not to communicate with each other.

そして、５，６は液分割部３によって二分された下流側流路２ｂの二つの部分２ｂ1 ，２ｂ2 の底部の表面に互いに離間した状態に形成される電極である。これらの電極５，６は、検体血液Ｓがアパーチャ２ｃを通過するときに生ずるインピーダンス変化を検出するためのもので、図２に示すように、計器本体（図示していない）の検出回路７に接続されている。そして、これらの電極５，６は、その平面視形状が台形状になるように、互いに線対称の状態で配置され、特に、台形の短い辺５ａ，６ａがアパーチャ２ｃに近くなるように配置されている。また、８，９は電極５，６にそれぞれ連なる電極リード部であり、これらの電極リード部８，９は流路２ａ，２ｂの底部と同レベルに位置するようにそれぞれ設けられる。 Reference numerals 5 and 6 denote electrodes formed on the surfaces of the bottoms of the two portions 2b 1 and 2b 2 of the downstream channel 2b divided by the liquid dividing unit 3 so as to be separated from each other. These electrodes 5 and 6 are for detecting a change in impedance that occurs when the sample blood S passes through the aperture 2c. As shown in FIG. 2, the electrodes 5 and 6 are connected to the detection circuit 7 of the instrument body (not shown). It is connected. The electrodes 5 and 6 are arranged in line symmetry with each other so that the shape in plan view is trapezoidal, and in particular, the trapezoidal short sides 5a and 6a are arranged close to the aperture 2c. ing. Reference numerals 8 and 9 denote electrode lead portions connected to the electrodes 5 and 6, respectively. These electrode lead portions 8 and 9 are provided so as to be located at the same level as the bottom portions of the flow paths 2a and 2b.

このため、シリコン基板１には、流路２ａ，２ｂと同じ深さのリード部用溝１０，１１が流路２ａ，２ｂと連なるようにして形成されている。これらのリード部用溝１０，１１は、流路２ａ，２ｂの形成時に同時にＭＥＭＳプロセスなどによる加工技術を用いて形成され、これらのリード部用溝１０，１１内には電極リード部８，９が電極５，６と同じ厚みで形成される。   For this reason, in the silicon substrate 1, lead portion grooves 10 and 11 having the same depth as the flow paths 2a and 2b are formed so as to be continuous with the flow paths 2a and 2b. These lead portion grooves 10 and 11 are formed by using a processing technique such as a MEMS process at the same time when the flow paths 2a and 2b are formed. In the lead portion grooves 10 and 11, the electrode lead portions 8 and 9 are formed. Is formed with the same thickness as the electrodes 5 and 6.

１２はシリコン基板１とほぼ同じ寸法を有する透明なガラス板で、流路２を覆うようにしてシリコン基板１に例えば陽極接合などの手法で接合される。そして、このガラス板１２がシリコン基板１に接合されることにより、流路２の各部２ａ〜２ｃは外部と遮断された状態で閉塞され、特に、狭隘部２ｃは、シリコン基板１と共働してアパーチャとなる。   A transparent glass plate 12 having substantially the same dimensions as the silicon substrate 1 is bonded to the silicon substrate 1 by a technique such as anodic bonding so as to cover the flow path 2. Then, the glass plate 12 is bonded to the silicon substrate 1, so that the portions 2 a to 2 c of the flow path 2 are blocked off from the outside. In particular, the narrow portion 2 c cooperates with the silicon substrate 1. And become an aperture.

１３，１４はガラス板１１に形成される検体血液導入孔、検体血液導出孔で、検体血液導入孔１３は、上流側流路２ａに対応する位置に開設され、また、検体血液導出孔１４は、下流側流路２ｂの二つの部分２ｂ1 ，２ｂ2 に対応する位置にそれぞれ開設されている。つまり、液分割部３によって二つに分割された検体血液Ｓは、互いに独立して取り出されるようにしてある。なお、これらの検体血液導入孔１３、検体血液導出孔１４は、検体血液導入用の流路（図示していない）、検体血液導出用の管路（図示していない）が着脱自在に接続されるように構成されている。 Reference numerals 13 and 14 denote a specimen blood introduction hole and a specimen blood outlet hole formed in the glass plate 11. The specimen blood introduction hole 13 is opened at a position corresponding to the upstream flow path 2a. , And are opened at positions corresponding to the two portions 2b 1 and 2b 2 of the downstream channel 2b. That is, the sample blood S divided into two by the liquid dividing unit 3 is taken out independently of each other. The specimen blood introduction hole 13 and the specimen blood lead-out hole 14 are detachably connected to a specimen blood introduction flow path (not shown) and a specimen blood lead-out pipe line (not shown). It is comprised so that.

１５，１６はガラス板１２に形成されるスルーホールで、電極リード部８，９のそれぞれの接続端部に一端が接続されたリード線１７，１８が挿通して、コネクタ１９の信号端子２０，２１に接続されている。なお、リード線１７，１８を挿通したスルーホール１５，１６には、耐水性および絶縁性を有する充填剤が充填され、液密構造が保持される。   15 and 16 are through-holes formed in the glass plate 12, and lead wires 17 and 18 having one ends connected to the connection ends of the electrode lead portions 8 and 9 are inserted, and the signal terminals 20 and 20 of the connector 19 are inserted. 21 is connected. In addition, the through holes 15 and 16 inserted through the lead wires 17 and 18 are filled with a filler having water resistance and insulation, and a liquid-tight structure is maintained.

前記コネクタ１９は、電極５，６によって検出されるインピーダンス変化を示す信号（検出信号）を外部に取り出すための接続装置で、シリコン基板１の側部に形成されており、所謂プラグインユニット形状に構成されている。そして、このコネクタ１９のコネクタ部２１は、信号ケーブル（図示していない）を介してマイクロ血球計数装置の計器本体（図示していない）に接続されている。   The connector 19 is a connection device for taking out a signal (detection signal) indicating an impedance change detected by the electrodes 5 and 6, and is formed on a side portion of the silicon substrate 1, and has a so-called plug-in unit shape. It is configured. The connector portion 21 of the connector 19 is connected to an instrument body (not shown) of the micro blood cell counter via a signal cable (not shown).

上記構成のマイクロ血球計数装置においては、適宜の希釈液で希釈された検体血液Ｓが検体血液導入孔１３から上流側流路２ａに導入される。この検体血液Ｓは、アパーチャ２ｃを経て下流側流路２ｂ側に流入する。この下流側流路２ｂに流入した検体血液Ｓは、アパーチャ２ｃに近接して設けられている液分割部３によって二つの流れに等分され、液分割部３によって分割された下流側流路の二つの部分２ｂ1 ，２ｂ2 内を流れる。そして、検体血液Ｓがアパーチャ２ｃと同様の隙間ｄ1 ，ｄ2 を通過するとき、インピーダンス変化が生じ、このインピーダンス変化が下流側流路２ｂの分割された部分２ｂ1 ，２ｂ2 に設けられた電極５，６によって検出され、このインピーダンス変化を表す信号は、電極リード部８，９、リード線１７，１８、コネクタ１９や信号ケーブル（図示していない）を経て計器本体（図示していない）に入力され、所定の演算が行われることにより、ＲＢＣ、ＷＢＣ、ＰＬＴなどの血球が計数される。なお、測定に供されたマイクロ血球カウンタは、原則として使い捨てにされる。 In the micro blood cell counter having the above configuration, the sample blood S diluted with an appropriate diluent is introduced from the sample blood introduction hole 13 into the upstream flow path 2a. The sample blood S flows into the downstream channel 2b side through the aperture 2c. The sample blood S flowing into the downstream channel 2b is equally divided into two flows by the liquid dividing unit 3 provided in the vicinity of the aperture 2c, and the downstream blood channel divided by the liquid dividing unit 3 It flows in the two parts 2b 1 and 2b 2 . When the sample blood S passes through the gaps d 1 and d 2 similar to the aperture 2c, an impedance change occurs, and this impedance change is provided in the divided portions 2b 1 and 2b 2 of the downstream flow path 2b. A signal that is detected by the electrodes 5 and 6 and represents this impedance change passes through the electrode lead portions 8 and 9, lead wires 17 and 18, a connector 19 and a signal cable (not shown), and an instrument body (not shown). Blood cells such as RBC, WBC, and PLT are counted. Note that the micro blood cell counter used for the measurement is in principle disposable.

そして、上記マイクロ血球計数装置においては、アパーチャ２ｃの下流側の流路２ｂに検体血液Ｓがアパーチャ２ｃを通過するするときに生ずるインーダンス変化を検出するための電極５，６を設けているので、仮に電極５，６において泡が生じても、この泡がアパーチャ２ｃを通過することがない。したがって、従来のこの種の装置と異なり、泡によるノイズが発生することがなくなり、精度の高い測定を行うことができる。そして、電極５，６間に印加する電圧を大きくすることができるので、より大きな検出信号が得られ、検出精度の高い測定を行うことができる。   In the micro blood cell counter, the electrodes 5 and 6 are provided in the flow path 2b on the downstream side of the aperture 2c for detecting the impedance change that occurs when the sample blood S passes through the aperture 2c. Even if bubbles are generated in the electrodes 5 and 6, the bubbles do not pass through the aperture 2c. Therefore, unlike conventional devices of this type, noise due to bubbles is not generated, and highly accurate measurement can be performed. Since the voltage applied between the electrodes 5 and 6 can be increased, a larger detection signal can be obtained and measurement with high detection accuracy can be performed.

上述の実施例においては、電極５，６の平面視形状を台形状に形成していたので、電界集中が緩和され、測定時のノイズを低減できるといった効果があるが、さらに、図３に示すように、前記電極５，６のアパーチャ２ｃ側の辺５ａ’，５ｂ’を曲線状（アパーチャ２ｃに向かって凸面状）に形成することにより、前記電界集中が緩和され、前記ノイズをより低減できる効果がある。   In the above-described embodiment, the shape of the electrodes 5 and 6 in plan view is formed in a trapezoidal shape, so that there is an effect that the electric field concentration is reduced and noise at the time of measurement can be reduced. As described above, by forming the sides 5a ′ and 5b ′ on the aperture 2c side of the electrodes 5 and 6 in a curved shape (convex shape toward the aperture 2c), the electric field concentration is alleviated and the noise can be further reduced. effective.

そして、この発明は、上記マイクロ血球計数装置に限られるものではなく、各種の液体中の微粒子を計数する装置においても広く適用することができる。   And this invention is not restricted to the said micro blood cell counter, It can apply widely also in the apparatus which counts the microparticles | fine-particles in various liquids.

この発明の液体中の微粒子計数装置としてのマイクロ血球計数装置の測定部におけるチップ構成を示す斜視図である。It is a perspective view which shows the chip | tip structure in the measurement part of the micro blood cell counter as a microparticle counter in the liquid of this invention. 前記測定部の要部の一例を拡大して示す平面図である。It is a top view which expands and shows an example of the principal part of the said measurement part. 前記測定部の要部の他の例を拡大して示す平面図である。It is a top view which expands and shows the other example of the principal part of the said measurement part. 従来技術を説明するための図である。It is a figure for demonstrating a prior art.

符号の説明Explanation of symbols

２ 流路 ２ａ 上流側流路 ２ｂ 下流側流路 ２ｃ アパーチャ ３ 液分割部 ５，６ 電極 Ｓ 液体試料 2 channel 2a upstream channel 2b downstream channel 2c aperture 3 liquid dividing part 5, 6 electrode S liquid sample

Claims (1)

液体試料が上流側から下流側に向かって流れる流路の途中にアパーチャを形成し、このアパーチャより下流側の流路に２個の電極を設けるとともに、前記下流側の流路の前記アパーチャの近傍に、前記アパーチャより上流側の流路から当該アパーチャを経て流れてくる液体試料を前記２つの電極方向に分割する液分割部を設け、前記液体試料が前記アパーチャを通過するときに生ずるインピーダンス変化を前記両電極によって検出し、この検出結果に基づいて前記液体試料中に含まれる粒子数を計数するようにしたことを特徴とする液体中の微粒子計数装置。
An aperture is formed in the middle of the flow path where the liquid sample flows from the upstream side toward the downstream side, and two electrodes are provided in the flow path on the downstream side of the aperture, and the vicinity of the aperture in the downstream flow path In addition, a liquid dividing unit that divides the liquid sample flowing from the flow path upstream of the aperture through the aperture in the direction of the two electrodes is provided, and an impedance change that occurs when the liquid sample passes through the aperture is provided. An apparatus for counting fine particles in a liquid, characterized in that the number of particles contained in the liquid sample is counted based on the detection result detected by the two electrodes.
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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2007017303A (en) * 2005-07-07 2007-01-25 Horiba Ltd Measuring instrument of number of cells and measuring cartridge of number of cells
JP4567540B2 (en) * 2005-07-07 2010-10-20 株式会社堀場製作所 Cell count device and cell count cartridge
US8961938B2 (en) 2005-09-05 2015-02-24 Kao Corporation Dentifrice composition
JP2013520659A (en) * 2010-02-26 2013-06-06 イーティーエイチ・チューリッヒ Method for spatially manipulating a micro object and apparatus for carrying out said method
JP2013015498A (en) * 2011-07-06 2013-01-24 Sharp Corp Particle measuring apparatus
EP2796855A1 (en) 2013-04-22 2014-10-29 Horiba, Ltd. Particle analysis apparatus and production method thereof
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US9581583B2 (en) 2013-05-17 2017-02-28 Horiba, Ltd. Blood analysis apparatus
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EP3336557A1 (en) 2016-12-15 2018-06-20 Horiba, Ltd.g Analysis apparatus
CN113917165A (en) * 2020-07-10 2022-01-11 深圳市帝迈生物技术有限公司 POCT sample analyzer and detection method thereof

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