KR20130062574A - Flexible ph sensor for measuring a ph in a blood vessel - Google Patents

Flexible ph sensor for measuring a ph in a blood vessel Download PDF

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KR20130062574A
KR20130062574A KR1020110128921A KR20110128921A KR20130062574A KR 20130062574 A KR20130062574 A KR 20130062574A KR 1020110128921 A KR1020110128921 A KR 1020110128921A KR 20110128921 A KR20110128921 A KR 20110128921A KR 20130062574 A KR20130062574 A KR 20130062574A
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flexible
sensor
substrate
electrode
blood vessel
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KR101301007B1 (en
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김진석
서준교
박형달
강성철
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한국과학기술연구원
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/14539—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue for measuring pH
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/14503—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/68—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
    • A61B5/6846—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive
    • A61B5/6847—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive mounted on an invasive device

Abstract

PURPOSE: A flexible pH sensor is provided to facilitate the insertion into the blood vessels, and to minimize the blood vessel damage by comprising flexible materials having biocompatibility. CONSTITUTION: A flexible pH sensor(100) comprises a substrate(110), a reference electrode(120), a working electrode(130), and ISFET(Ion-Selective Field Effect Transistor)(140). The substrate has the biocompatibility, and is made of flexible materials. The substrate is formed with the width and length of 300um to 500um, respectively. The reference electrode and the working electrode are formed by photolithography and a lift-off process on the substrate, and perform the pH measurement in the blood vessels. The ISFET is formed between the reference electrode and the working electrode, and the two electrodes are in a semiconductor electrode form.

Description

혈관 내 피에이치 측정을 위한 플렉시블 피에이치 센서 {FLEXIBLE PH SENSOR FOR MEASURING A PH IN A BLOOD VESSEL}FLEXIBLE PH SENSOR FOR MEASURING A PH IN A BLOOD VESSEL}

본 발명은 플렉시블 pH 센서에 관한 것으로, 더 상세하게는, 생체적합성을 갖는 유연한 재료를 이용하며 의학용 주사바늘을 이용하여 혈관 삽입이 용이한 크기를 갖는 플렉시블 pH 센서에 관한 것이다. The present invention relates to a flexible pH sensor, and more particularly, to a flexible pH sensor using a flexible material having biocompatibility and having an easy insertion of blood vessels using a medical needle.

pH 센서는 용액의 pH를 측정하기 위한 센서이며, 근래에는 pH 센서를 소형화하여 임상의학의 분야에서 모니터용으로서 사용하고 있다. 특히, 뇌 수술 시에 있어서, 뇌는 산소 공급이 중단되면 기능이 정지하고, 이 상태가 지속되면 4~5분 내에 재생불능의 뇌세포 파괴가 일어나므로, 뇌에 공급되는 산소를 실시간으로 모니터링 할 필요성이 크다. The pH sensor is a sensor for measuring the pH of a solution. In recent years, the pH sensor has been miniaturized and used as a monitor in the field of clinical medicine. In particular, during brain surgery, the brain ceases to function when oxygen supply is interrupted, and if this condition persists, non-renewable brain cell destruction occurs within 4 to 5 minutes. The need is great.

신체는 정상일 때, 혈액 내의 이산화탄소와 산소의 분압이 일정하게 유지되지만, 산소 공급이 충분하지 못한 경우, 혈액의 이산화탄소 분압이 상승하게 된다. 이 상태에서, 혈중 이산화탄소가 뇌 장벽을 통과하여 뇌척수액에 유입되며, 뇌척수액의 물(H2O)과 결합하여 H+ 이온을 발생시켜 뇌척수액의 pH 농도가 낮아지게 된다. 상기와 같은 뇌척수액의 pH 의 측정을 위해, 종래에는 뇌하수체에 pH 센서를 삽입하여 측정하였으나, 이 경우, 뇌수술시 위험성이 크고, 수술부위에서 이뤄지는 워싱(washing)이나 흡입(suction)과 같은 행위로 인해서 정확한 pH 농도 측정이 어렵다는 문제점이 있다. When the body is normal, the partial pressure of carbon dioxide and oxygen in the blood is kept constant, but when the oxygen supply is insufficient, the partial pressure of carbon dioxide in the blood rises. In this state, blood carbon dioxide enters the cerebrospinal fluid through the brain barrier, and combines with cerebrospinal fluid water (H 2 O) to generate H + ions, thereby lowering the pH of the cerebrospinal fluid. In order to measure the pH of the cerebrospinal fluid as described above, in the past, a pH sensor was inserted into the pituitary gland, but in this case, the risk of brain surgery is high, and the acts such as washing or suction performed at the surgical site are performed. Due to this, there is a problem in that accurate pH concentration measurement is difficult.

도 1은 종래의 pH 모니터링 장치를 도시하는 도면이다. 1 is a view showing a conventional pH monitoring device.

도 1을 참조하면, 뇌의 pH 모니터링을 위해, 종래의 논문, 뇌의 pH 체내 모니터링을 위한 새로운 ISFET 카테테르 피막형성 기술(NEW ISFET CATHETERS ENCAPSULATION TECHNIQUES FOR BRAIN PH IN-VIVO MONITORING)은, 기존의 pH 센서에 사용되는 Ag/AgCl/KCL 용액이 아닌 은(silver) 전극, 즉, 고체 박막형 전극을 이용한 pH 센서가 집적된 카테테르를 이용하여, 임상학적으로 혈관을 통한 pH 모니터링 가능성을 제시한다. Referring to Figure 1, for the pH monitoring of the brain, the conventional paper, the new ISFET CATHETERS ENCAPSULATION TECHNIQUES FOR BRAIN PH IN-VIVO MONITORING The use of a catheter integrated with a silver sensor, ie, a solid-state thin film electrode, rather than a Ag / AgCl / KCL solution used in the sensor, suggests the possibility of clinically monitoring pH through blood vessels.

그러나, 상기 논문에서 제안된 카테테르의 경우, 특정 혈관에만 삽입이 가능한 크기를 가지고 있으므로, 사용에 있어서 제약이 따른다. 또한, 카테테르가 혈관에 삽입 시, 카테테르의 강성(rigidity)으로 인해 혈관 손상이 야기될 수 있으며, 크기로 인해서 혈관 내 혈액이 흐를 수 있는 공간을 협소하게 만들어, 혈액의 흐름을 방해하여 뇌압이 상승하는 역효과를 일으키기도 한다.However, the catheter proposed in the above paper has a size that can be inserted only into a specific blood vessel, and thus there is a limitation in use. In addition, when the catheter is inserted into the blood vessel, the rigidity of the catheter may cause damage to the blood vessel, and the size of the catheter narrows the space where blood can flow in the blood vessel, thereby interfering with the flow of blood, thereby causing pressure. This rising adverse effect may also occur.

따라서, 혈관 손상을 최소화하면서, 혈액의 pH 농도 측정을 용이하게 수행할 수 있는 기술이 요구된다.Therefore, there is a need for a technique that can easily measure the pH concentration of blood while minimizing blood vessel damage.

비특허문헌 1: NEW ISFET CATHETERS ENCAPSULATION TECHNIQUES FOR BRAIN PH IN-VIVO MONITORING : Liby Sudakov-Boreysha et al., IEEE 2004, 424-426면Non-Patent Document 1: NEW ISFET CATHETERS ENCAPSULATION TECHNIQUES FOR BRAIN PH IN-VIVO MONITORING: Liby Sudakov-Boreysha et al., IEEE 2004, pp. 424-426

본 발명의 목적은 의학용 주사바늘을 통해 혈관 내에 삽입가능한 크기를 갖는 생체적합성을 지닌 플렉시블 pH 센서를 제공하는 것이다.It is an object of the present invention to provide a biocompatible flexible pH sensor having a size that can be inserted into a blood vessel through a medical needle.

전술한 목적을 달성하기 위한 본 발명의 일 실시예에 따른 플렉시블 pH 센서는, 유연한 재료로 이루어지는 기판; 상기 기판 상에 포토리소그래피와 리프트-오프 공정을 통해 형성되어 pH 농도 측정을 수행하는 기준 전극과 작용 전극; 및 상기 기준 전극과 작용 전극 사이에 형성되는 ISFET를 포함하며, 상기 기판은 의학용 주사바늘에 삽입가능하도록 가로와 세로 크기가 각각 300㎛ 내지 500㎛ 로 이루어진다. Flexible pH sensor according to an embodiment of the present invention for achieving the above object, a substrate made of a flexible material; A reference electrode and a working electrode formed on the substrate through photolithography and lift-off processes to perform pH concentration measurement; And an ISFET formed between the reference electrode and the working electrode, wherein the substrate has a horizontal and vertical size of 300 µm to 500 µm, respectively, so as to be inserted into a medical needle.

상기 기판은 후막 포토레지스트 또는 고분자 물질로 이루어질 수 있다. The substrate may be made of a thick film photoresist or a polymer material.

상기 기준 전극은 Au 전극이 될 수 있다. The reference electrode may be an Au electrode.

상기 작용 전극은 나노다공성 금속으로 이루어질 수 있다.The working electrode may be made of a nanoporous metal.

본 발명의 플렉시블 pH 센서는 생체적합성을 갖는 유연한 재료로 구성되므로, 혈관 내에 삽입이 용이하며 혈관 손상도 최소화할 수 있는 효과가 있다. Since the flexible pH sensor of the present invention is composed of a flexible material having biocompatibility, it is easy to insert into a blood vessel and has an effect of minimizing blood vessel damage.

또한, 본 발명의 플렉시블 pH 센서는 의학용 주사바늘을 통해 혈관 내에 삽입가능한 크기를 가지므로, 사용이 편리하다는 효과가 있다.In addition, the flexible pH sensor of the present invention has a size that can be inserted into the blood vessel through the medical needle, there is an effect that it is convenient to use.

도 1은 종래의 pH 모니터링 장치를 도시하는 도면이다.
도 2는 본 발명의 일 실시예에 따른 플렉시블 pH 센서를 도시한 사시도이다.
도 3은 도 2의 플렉시블 pH 센서의 단면도이다.
도 4는 본 발명의 플렉시블 pH 센서가 의학용 주사바늘을 이용하여 혈관 내에 삽입된 상태를 도시하는 도면이다. 1 is a view showing a conventional pH monitoring device.
2 is a perspective view showing a flexible pH sensor according to an embodiment of the present invention.
3 is a cross-sectional view of the flexible pH sensor of FIG. 2.
4 is a view illustrating a state in which the flexible pH sensor of the present invention is inserted into a blood vessel using a medical needle.

이하에서는 첨부한 도면을 참조하여 본 발명의 바람직한 실시예에 따른 플렉시블 pH 센서에 대하여 상세히 설명한다. Hereinafter, a flexible pH sensor according to a preferred embodiment of the present invention will be described in detail with reference to the accompanying drawings.

도 2는 본 발명의 일 실시예에 따른 플렉시블 pH 센서를 도시한 사시도이며, 도 3은 도 2의 플렉시블 pH 센서의 단면도이다. 2 is a perspective view showing a flexible pH sensor according to an embodiment of the present invention, Figure 3 is a cross-sectional view of the flexible pH sensor of FIG.

도 2 및 도 3을 참조하면, 본 발명의 플렉시블 pH 센서(100)는, 기판(110), 기준 전극(reference electrode)(120), 작용 전극(working electrode)(130) 및 ISFET(Ion-Selective Field Effect Transistor)(140)을 포함한다. 2 and 3, the flexible pH sensor 100 of the present invention includes a substrate 110, a reference electrode 120, a working electrode 130, and an ion selective (ISFET). Field Effect Transistor) 140.

기판(110)은 생체적합성을 가지며, 유연한 재료로 이루어진다. 또한, 기판(110)은 의학용 주사바늘의 내경에 삽입가능한 크기로 제조되며, 예를 들어, 가로와 세로 크기는 각각 300㎛ 내지 500㎛로 구성된다. The substrate 110 is biocompatible and is made of a flexible material. In addition, the substrate 110 is made of a size that can be inserted into the inner diameter of the medical needle, for example, the horizontal and vertical size is composed of 300㎛ to 500㎛, respectively.

본 발명의 플렉시블 pH 센서(100)는 기판(110)이 유연한 물질로 구성되므로, 혈관에 삽입 시 혈관 손상을 최소화할 수 있고, 의학용 주사바늘에 끼워서, 혈관 내로 삽입하므로 그 사용이 편리하다. 기판(110)은, 예를 들어, SU-8과 같은 후막 포토레지스트(thick photoresist) 또는 폴리이미드(polyimide)와 같은 고분자 물질로 이루어질 수 있다.Flexible pH sensor 100 of the present invention is because the substrate 110 is made of a flexible material, can minimize the damage to the blood vessel when inserted into the blood vessel, inserted into the medical needle, it is convenient to use because it is inserted into the blood vessel. The substrate 110 may be made of, for example, a polymer material such as a thick photoresist or polyimide such as SU-8.

기준 전극(120)과 작용 전극(130)은 혈관 내 pH 농도 측정을 수행한다. 기준 전극(120)과 작용 전극(130) 사이에는 ISFET(Ion-Selective Field Effect Transistor)(140)가 형성되어, 2개의 전극(120, 130)이 반도체 전극의 형태가 된다. 따라서, 기준 전극(120)과 작용 전극(130)은 ISFET(140)의 소스/드레인 구조를 갖게 되며, 혈관 내 pH 변화에 따라 2개의 전극(120, 130) 사이에 드레인 전류의 변화가 발생하여, 이를 통해 혈관 내 pH 값을 구분한다. The reference electrode 120 and the working electrode 130 perform intravascular pH concentration measurement. An ion-selective field effect transistor (ISFET) 140 is formed between the reference electrode 120 and the working electrode 130 so that the two electrodes 120 and 130 are in the form of semiconductor electrodes. Accordingly, the reference electrode 120 and the working electrode 130 have a source / drain structure of the ISFET 140, and a change in drain current occurs between two electrodes 120 and 130 according to a change in pH in a blood vessel. In this way, the pH value of blood vessels can be distinguished.

pH 농도 측정은 기준 전극(120)과 작용 전극(130)에서 드레인 전류가 형성되는 전극의 전류를 측정하여, 전류 차이에 따라 pH 농도 측정 결과를 산출한다. 이를 위해, 제조된 플렉시블 pH 센서(100)의 감도(sensitivity)에 따른 농도별 데이터 피드백이 필요하다. The pH concentration measurement measures the current of the electrode in which the drain current is formed in the reference electrode 120 and the working electrode 130, and calculates the pH concentration measurement result according to the current difference. To this end, concentration-specific data feedback based on the sensitivity of the manufactured flexible pH sensor 100 is required.

기준 전극(120)은 Au 전극으로 구성될 수 있으며, 작용 전극(130)은 나노다공성 금속(nanoporous metal)으로 구성될 수 있다. 상기 Au 전극과 나노다공성 금속은 기판(110) 상에 포토리소그래피(photolithography)와 리프트-오프(lift-off) 공정 방식을 적용하여 형성할 수 있다. The reference electrode 120 may be formed of an Au electrode, and the working electrode 130 may be formed of a nanoporous metal. The Au electrode and the nanoporous metal may be formed on the substrate 110 by applying photolithography and a lift-off process method.

구체적으로, Au 전극은 이-빔 증착(E-beam evaporation)이나 스퍼터링(sputtering)을 이용하여 기판(110) 상에 증착할 수 있으며, 나노다공성 금속은, 스퍼터링에서 기체(O2) 삽입량을 조절하거나, 나노-파티클을 이용하거나, 전기 도금(electrodeposition) 방식을 이용하거나, 졸-겔(sol-gel) 방식을 통해 기판(110) 상에 형성될 수 있다. 이 중, 스퍼터링에서 기체(O2) 삽입량을 조절하는 방식을 채택하는 경우, 기존의 보유 장비를 이용하여 조건 확립을 통해 나노다공성 금속을 형성할 수 있다. Specifically, the Au electrode may be deposited on the substrate 110 by using E-beam evaporation or sputtering, and the nanoporous metal may adjust the amount of gas (O 2 ) insertion in sputtering. It may be formed on the substrate 110 by adjusting, using nano-particles, using an electrodeposition method, or a sol-gel method. Among these, in the case of adopting a method of adjusting the amount of gas (O 2) inserted in the sputtering, it is possible to form the nanoporous metal through the establishment of conditions using existing holding equipment.

본 발명의 플렉시블 pH 센서(100)는 액체 전극을 배제하고, 기준 전극(120)과 작용 전극(130)을 각각 Au 전극과 나노다공성 금속으로 구성함으로써, 생체적합성을 갖게 된다. The flexible pH sensor 100 of the present invention has a biocompatibility by excluding the liquid electrode and configuring the reference electrode 120 and the working electrode 130 each with an Au electrode and a nanoporous metal.

본 발명의 플렉시블 pH 센서(100)는, 예를 들어, 내경정맥 내에 삽입될 수 있으며, 뇌하수체의 pH 농도는 뇌에 공급되는 산소량에 대한 정보를 나타낸다. 본 발명의 플렉시블 pH 센서(100)를 뇌하수체에 삽입하는 경우, 뇌하수체에 pH 센서를 직접 삽입하는 종래의 방식보다 뇌수술시 위험성이 적고, 수술부위에서 이뤄지는 워싱(washing)이나 흡입(suction)과 같은 행위로 인해서 정확한 pH 농도 측정이 방해되는 것도 방지할 수 있다. 따라서, 뇌 수술 시에, 내경정맥의 pH 농도를 측정함으로써 보다 정확하게 환자의 뇌에 공급되는 산소량을 추정할 수 있으므로, 본 발명의 플렉시블 pH 센서(100)는 뇌의 산소결핍 상태를 실시간으로 모니터링 할 수 있도록 한다. The flexible pH sensor 100 of the present invention may be inserted into, for example, the internal jugular vein, and the pH concentration of the pituitary gland indicates information on the amount of oxygen supplied to the brain. When inserting the flexible pH sensor 100 of the present invention into the pituitary gland, there is less risk during cerebral surgery than the conventional method of inserting the pH sensor directly into the pituitary gland, such as washing or suction performed at the surgical site Actions can also prevent interference with accurate pH concentration measurements. Therefore, since the amount of oxygen supplied to the patient's brain can be estimated more accurately by measuring the pH concentration of the internal jugular vein during brain surgery, the flexible pH sensor 100 of the present invention can monitor the oxygen deficiency state of the brain in real time. To help.

도 4는 본 발명의 플렉시블 pH 센서가 혈관 내에 삽입된 상태를 도시하는 도면이다. 4 is a view showing a state where the flexible pH sensor of the present invention is inserted into the blood vessel.

도 4를 참조하면, 전술한 바와 같이 본 발명의 플렉시블 pH 센서(100)는 의학용 주사바늘(200)에 끼워진 상태에서 혈관(300) 내로 삽입가능하므로, pH 센서(100)의 배치 및 사용이 용이하다. Referring to FIG. 4, as described above, the flexible pH sensor 100 of the present invention can be inserted into the blood vessel 300 in a state of being fitted to the medical needle 200, so that the placement and use of the pH sensor 100 may be avoided. It is easy.

상기에서는 본 발명의 바람직한 실시예에 대하여 설명하였지만, 본 발명은 이에 한정되는 것이 아니고 특허청구범위와 발명의 상세한 설명 및 첨부한 도면의 범위 안에서 여러 가지로 변형하여 실시하는 것이 가능하고 이 또한 본 발명의 범위에 속하는 것은 당연하다.While the present invention has been described in connection with what is presently considered to be practical exemplary embodiments, it is to be understood that the invention is not limited to the disclosed embodiments, but, on the contrary, Of course.

100: 플렉시블 pH 센서
110: 기판
120: 기준 전극
130: 작용 전극
140: ISFET
200: 의학용 주사바늘
300: 혈관100: flexible pH sensor
110: substrate
120: reference electrode
130: working electrode
140: ISFET
200: medical needle
300: blood vessel

Claims (4)

혈관 내 pH 측정을 위한 플렉시블 pH 센서로서,
유연한 재료로 이루어지는 기판;
상기 기판 상에 포토리소그래피와 리프트-오프 공정을 통해 형성되어 pH 농도 측정을 수행하는 기준 전극과 작용 전극; 및
상기 기준 전극과 작용 전극 사이에 형성되는 ISFET를 포함하며,
상기 기판은 의학용 주사바늘에 삽입가능하도록 가로와 세로 크기가 각각 300㎛ 내지 500㎛ 인 것을 특징으로 하는 플렉시블 pH 센서.Flexible pH sensor for pH measurement in blood vessels,
A substrate made of a flexible material;
A reference electrode and a working electrode formed on the substrate through photolithography and lift-off processes to perform pH concentration measurement; And
An ISFET formed between the reference electrode and the working electrode,
The substrate is a flexible pH sensor, characterized in that the horizontal and vertical size is 300㎛ to 500㎛ respectively so as to be inserted into the medical needle. 제1항에 있어서, 상기 기판은 후막 포토레지스트 또는 고분자 물질로 이루어지는 것을 특징으로 하는 플렉시블 pH 센서.The flexible pH sensor of claim 1, wherein the substrate is made of a thick film photoresist or a polymer material. 제1항에 있어서, 상기 기준 전극은 Au 전극인 것을 특징으로 하는 플렉시블 pH 센서. The flexible pH sensor of claim 1, wherein the reference electrode is an Au electrode. 제1항에 있어서, 상기 작용 전극은 나노다공성 금속으로 이루어지는 것을 특징으로 하는 플렉시블 pH 센서.The flexible pH sensor of claim 1, wherein the working electrode is made of a nanoporous metal.
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