CN212546944U - A sensor for minimally invasive detection of levodopa - Google Patents
A sensor for minimally invasive detection of levodopa Download PDFInfo
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- CN212546944U CN212546944U CN202020511116.2U CN202020511116U CN212546944U CN 212546944 U CN212546944 U CN 212546944U CN 202020511116 U CN202020511116 U CN 202020511116U CN 212546944 U CN212546944 U CN 212546944U
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- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 title claims abstract description 47
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- 229960004502 levodopa Drugs 0.000 title claims abstract description 47
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- 239000010931 gold Substances 0.000 claims description 8
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- AHMIDUVKSGCHAU-LURJTMIESA-N L-dopaquinone Chemical compound [O-]C(=O)[C@@H]([NH3+])CC1=CC(=O)C(=O)C=C1 AHMIDUVKSGCHAU-LURJTMIESA-N 0.000 description 3
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- Measurement Of The Respiration, Hearing Ability, Form, And Blood Characteristics Of Living Organisms (AREA)
Abstract
本实用新型公开了一种微创检测左旋多巴的传感器。该传感器包含有一基底，基底下平面固定有三根针形电极，其分别为第一工作电极，第二工作电极，以及参比电极。三根针形电极上端均连接着导电片，在导电片上端固定有一块印刷电路板，电极的信号可以通过导电片与印刷电路板的触点连接。本实用新型在使用过程中，三根针形电极刺入并停留在人体皮肤的浅表层，以此来持续将体液中探测到的反应电流输出，由于第一工作电极与第二工作电极表面修饰有不同的涂层，因此可以通过差分的方式计算得到左旋多巴的浓度，从而实现微创连续检测左旋多巴浓度。
The utility model discloses a sensor for minimally invasive detection of levodopa. The sensor includes a base, and three needle electrodes are fixed on the lower plane of the base, which are respectively a first working electrode, a second working electrode and a reference electrode. The upper ends of the three needle electrodes are all connected with a conductive sheet, and a printed circuit board is fixed on the upper end of the conductive sheet. The signals of the electrodes can be connected to the contacts of the printed circuit board through the conductive sheet. During the use of the utility model, the three needle electrodes pierce and stay on the superficial layer of the human skin, so as to continuously output the reaction current detected in the body fluid. Because the surfaces of the first working electrode and the second working electrode are decorated with Different coatings, therefore, the concentration of levodopa can be calculated in a differential manner, thereby realizing minimally invasive continuous detection of levodopa concentration.
Description
Technical Field
The utility model belongs to the technical field of medical monitoring instrument, more specifically say, relate to a minimally invasive detection levodopa's sensor.
Background
Parkinson is a common degenerative disease of the nervous system caused by a deficiency in the neurotransmitter dopamine, with an average age of around 60 years, and patients often exhibit resting tremor, bradykinesia, rigidity, and postural gait disturbance. Since 1960, levodopa (L-DOPA) was used as the most effective drug for the treatment of parkinson's disease. Because the levodopa is a metabolic precursor of the dopamine, the levodopa can pass through a blood brain barrier, but the dopamine cannot pass through the blood brain barrier, and the dopamine can be effectively improved by taking the levodopa medicine. However, long-term use of levodopa will also increase the concentration of levodopa in blood, which in turn may cause other adverse effects such as dyskinesia. Therefore, it is important to detect and control the concentration of levodopa in the blood during treatment.
Several assays currently used to detect levodopa include: spectrophotometry, gas chromatography, high performance liquid chromatography, etc., which all require long-term analysis and have poor real-time performance and cannot be used for dynamically monitoring the concentration of levodopa in blood.
The electrochemical detection method is researched and used for monitoring levodopa nowadays due to the advantages of high sensitivity, low manufacturing cost and the like. At present, the biggest difficulty in measuring the levodopa content in a living body by an electrochemical method is the influence of interferents such as ascorbic acid, glucose, uric acid and the like coexisting with the levodopa.
Disclosure of Invention
The utility model provides a minimally invasive detection levodopa's sensor to the above-mentioned not enough of prior art existence. A first working electrode, a second working electrode and a reference electrode of the sensor are pierced into and stay on the superficial layer of human skin, a first working electrode generates a target signal and an interference signal, a second working electrode generates an interference signal, and the two signals are differentiated, so that interference is eliminated, and levodopa is continuously monitored.
The utility model provides a technical scheme that its technical problem adopted as follows:
a minimally invasive levodopa detection sensor comprises a base and an insulating top cover, wherein the base and the insulating top cover form a sensor inner cavity, a printed circuit board is installed in the sensor inner cavity, and a first needle-shaped working electrode, a second needle-shaped working electrode and a reference electrode are fixed on the bottom surface of the base; the fixed ends of the first needle-shaped working electrode, the second needle-shaped working electrode and the reference electrode are respectively connected with corresponding signal contacts on the printed circuit board through different conducting strips, and the tips of the first needle-shaped working electrode, the second needle-shaped working electrode and the reference electrode all protrude out of the bottom surface of the base; the first needle-shaped working electrode, the second needle-shaped working electrode and the reference electrode form a double-electrode system respectively;
the first needle-shaped working electrode is of a multi-layer composite structure, the center of the first needle-shaped working electrode is a first metal needle core, and a first catalytic metal layer and a first biocompatible polymer permeation film layer are sequentially wrapped outside the first metal needle core;
the second needle-shaped working electrode is of a multi-layer composite structure, the center of the second needle-shaped working electrode is a second metal needle core, and a second catalytic metal layer, a tyrosinase layer and a second biocompatible polymer permeation film layer are sequentially wrapped outside the second metal needle core.
Preferably, the first metal stylet and/or the second metal stylet is made of gold.
Preferably, the first catalytic metal layer and/or the second catalytic metal layer are gold nanoparticles.
Preferably, the first biocompatible polymer permeable membrane layer and/or the second biocompatible polymer permeable membrane layer is a polyurethane layer.
Preferably, the reference electrode is a silver/silver chloride electrode.
Preferably, the edge portion of the bottom surface of the base is adhered with a ring of adhesive tape for adhering and fixing the sensor on the skin surface.
Preferably, the first needle-shaped working electrode, the second needle-shaped working electrode and the reference electrode are detachably fixed to the base.
Compared with the prior art, the utility model discloses following beneficial effect has:
the utility model discloses can utilize three aciculiform electrodes to pierce and stop at the superficial top layer of human skin to this continues the reaction current output who detects in the body fluid, because two working electrode surface modification have different coatings, consequently can calculate the concentration that obtains levodopa through the mode of difference, thereby realizes the wicresoft and detects levodopa concentration in succession. The utility model discloses got rid of the interference that exists in the body fluid, realized continuously surveying levodopa concentration in the body fluid and can continuous output, effective control parkinson patient dosage is at a suitable level.
Drawings
Fig. 1 is a schematic view of the overall structure of the present invention;
fig. 2 is an exploded view of the present invention;
FIG. 3 is a schematic view of a first needle-shaped working electrode of the present invention;
FIG. 4 is a schematic view of a second needle-shaped working electrode of the present invention;
fig. 5 is a graph of current values for the first and second needle-shaped working electrodes at different concentrations of levodopa.
The reference numbers in the figures are: the biosensor comprises a base 1, a first needle-shaped working electrode 2, a reference electrode 3, a second needle-shaped working electrode 4, a conducting strip 5, a printed circuit board 6, an insulating top cover 7, a first metal needle core 2.1, a first metal catalyst layer 2.2, a first biocompatible polymer permeation membrane layer 2.3, a second metal needle core 4.1, a second metal catalyst layer 4.2, a second biosensing layer 4.3 and a second biocompatible polymer permeation membrane layer 4.4.
Detailed Description
The following description will be made in detail with reference to the accompanying drawings, which are implemented on the premise of the technical solution of the present invention, and the detailed embodiments and the specific operation process are given, but the scope of the present invention is not limited to the following examples.
As shown in fig. 1 and 2, in a preferred embodiment of the present invention, a sensor for minimally invasive detection of levodopa is provided, in which a base 1 and an insulating cap 7 are provided. The base 1 is a mounting frame of the entire sensor and has a plate shape. A first needle-shaped working electrode 2, a second needle-shaped working electrode 4 and a reference electrode 3 are fixed on the bottom surface of the base 1. The three electrodes are vertically mounted on the bottom surface of the base 1 with their tips facing downward. In use, the tips of the three electrodes pierce the skin and are fixed to the superficial layer of the skin. The fixed ends of the first needle-shaped working electrode 2, the second needle-shaped working electrode 4 and the reference electrode 3 are respectively connected with metal contacts for signal input on a printed circuit board 6 through different conducting strips 5. Thus, the first needle-shaped working electrode 2 and the reference electrode 3, and the second needle-shaped working electrode 2 and the reference electrode 3 constitute two-electrode systems, respectively. The two double-electrode systems respectively generate different electrochemical reactions in body fluid and generate electric signals, the electric signals are transmitted to a printed circuit board 6, an electric insulation top cover 7 made of plastic materials is assembled on the base 1, and the printed circuit board 6 is internally arranged and packaged in a sensor inner cavity formed by the two parts. In order to enhance the fixing effect, a circle of adhesive plaster is arranged at the edge position of the base 1 and can be fixed on the skin of a human body, and the adhesive plaster can adopt products such as medical double-sided adhesive tape or adhesive gel.
For convenience of use, the base 1 is provided with a groove on the bottom surface, three electrode mounting holes are formed in the groove, and the first needle-shaped working electrode 2, the second needle-shaped working electrode 4 and the reference electrode 3 are uniformly arranged in the groove. The fixed end of each electrode passes through the electrode mounting hole for fixing, and the tip of each electrode needs to protrude out of the bottom surface of the base 1 so as to be capable of penetrating into the skin. The protruding length of the tip needs to be set properly to allow contact with body fluids in the superficial layers of the skin, but not to penetrate too deeply to avoid excessive loss of skin tissue. In addition, as shown in fig. 2, each electrode of the present invention can be detachably mounted or attached to the bottom surface of the base 1, the conductive sheet 5 matched with the electrode can be set to a clamping member, and the fixed end of the electrode can be fixed on the base 1 by using the conductive sheet 5. When the sequential detection process is completed, the detection device can be detached and replaced, and the base 1, the conducting strip 5 and the printed circuit board are multiplexed, so that the use cost is reduced.
In the two-electrode systems, the working electrodes are wrapped by different composite structures, so that the electrochemical reactions are different. As shown in fig. 3, the first needle-shaped working electrode has a multi-layer composite structure, a first metal needle core 2.1 is disposed at the center, and a first catalytic metal layer 2.2 and a first bio-compatible polymer permeation film layer 2.3 are sequentially wrapped outside the first metal needle core 2.1. In this example, the first metal needle core 2.1 is made of gold, the first catalytic metal layer 2.2 is a gold nanoparticle layer, and the first biocompatible polymer permeation membrane layer 2.3 is a polyurethane Pu layer. Interference substances such as levodopa and ascorbic acid in body fluid are subjected to oxidation-reduction reaction under the applied voltage of 0.3V, and then an electric signal is generated and transmitted outwards through the first metal needle core 2.1. As shown in fig. 4, the second needle-shaped working electrode 4 is also a multi-layer composite structure, the center of which is a second metal needle core 4.1, and the second metal needle core 4.1 is sequentially wrapped with a second catalytic metal layer 4.2, a tyrosinase layer 4.3 and a second biocompatible polymer permeation membrane layer 4.4. In this example, the second metallic needle core 4.1 is gold, the second catalytic metallic layer 4.2 is a gold nanoparticle layer, the tyrosinase layer 4.3 is a biosensing layer, and the second biocompatible polymer permeation membrane layer 4.4 is a polyurethane Pu layer. Levodopa in body fluid permeates through the Pu layer and reacts with tyrosinase in the biosensing layer to generate dopaquinone. And the interference substances such as ascorbic acid and the like still generate oxidation reduction reaction under the applied voltage of 0.3V, and further generate an electric signal, and the electric signal is transmitted outwards through the second metal needle core 4.1. Thus, the difference between the electrical signals of the two working electrodes is the redox potential caused by dopaquinone produced by the tyrosinase reaction. As shown in fig. 5, the current values of the first needle-shaped working electrode 2 and the second needle-shaped working electrode 4 at different concentrations of levodopa are calculated by differentiating the electrical signals of the two electrodes, and the concentration of levodopa in the body fluid can be converted from the differential signal.
In the present invention, the reference electrode can be formed by any silver/silver chloride electrode of the prior art, but in this example, the inner needle core is silver and the surface of the reference electrode is compounded with a silver/silver chloride layer.
The utility model discloses in, first aciculiform working electrode, second aciculiform working electrode and reference electrode's effect are the electrochemistry signal who obtains relevant reaction in the body fluid, and printed circuit board's effect is the signal of telecommunication that the receiving electrode gathered and carries out corresponding processing to the signal. The specific form and circuit structure of printed circuit board can design according to required function, also can adopt current commercial product, not the utility model discloses a key. Generally, a constant potential circuit, a bluetooth antenna, a metal contact, a microprocessor, a peripheral circuit and a lithium battery are required to be arranged on the printed circuit board. The electric signal that the electrode was gathered needs to be transmitted to the microprocessor of printed circuit board through the metal contact in, then in transmitting to corresponding host computer through bluetooth antenna wireless. It should be noted that the above sensor of the present invention does not need to calculate the concentration of levodopa, and it mainly detects the corresponding electrical signal, and the subsequent signal processing and calculation can be realized by an external system.
Therefore, the utility model discloses based on above-mentioned sensor, can further provide a levodopa detecting system, it contains above-mentioned sensor and host computer, and the sensor is connected through the bluetooth with the host computer and is carried out data transmission. Of course, the sensor and the upper computer may be connected in other wired or wireless manners. In this system, the sensor is first fixed to the skin surface and three electrodes penetrate the superficial layer of the skin to contact the body fluid. The same electric potential is applied to two double-electrode systems formed by the three electrodes, so that the oxidation-reduction reaction electric signals of the two double-electrode systems to the body fluid to be detected can be respectively obtained and sent to an upper computer. As mentioned above, in the two-electrode systems, the working electrodes are wrapped by different composite structures, so that the electrochemical reactions are different, wherein the first needle-shaped working electrode 2 obtains the basic current I of the body fluid under the applied voltage1The current is generated by oxidation-reduction reaction of interference substances such as levodopa and ascorbic acid; the second needle-shaped working electrode 4 is also provided with the tyrosinase layer 4.3, so that the detection current I under the applied voltage after the dopaquinone is generated by catalyzing the levodopa in the body fluid by the tyrosinase layer 4.3 can be obtained2. A computing unit in the upper computer obtains a basic current I1And detecting the current I2Then, the differential current Δ I ═ I of the two is calculated1-I2According to the advanceAnd calculating a conversion formula between the stored differential current and the concentration of the levodopa to obtain the concentration of the levodopa in the body fluid to be detected.
The utility model discloses in, a concentration conversion formula for data processing can be obtained by the data fitting, and it is the fitting formula between the levodopa concentration in differential current and the sample. The sensor can be used for measuring body fluid containing levodopa with different concentrations, response current is detected under an external constant potential, and a straight line is fitted to obtain a conversion relation between the levodopa concentration of the body fluid to be measured and the differential current of the body fluid to be measured.
The above-mentioned embodiments are merely a preferred embodiment of the present invention, but it is not intended to limit the present invention. Various changes and modifications can be made by one of ordinary skill in the pertinent art without departing from the spirit and scope of the present invention. Therefore, all the technical schemes obtained by adopting the mode of equivalent replacement or equivalent transformation fall within the protection scope of the utility model.
Claims (7)
1. A minimally invasive levodopa detection sensor is characterized by comprising a base (1) and an insulating top cover (7), wherein the base (1) and the insulating top cover form a sensor inner cavity, a printed circuit board (6) is installed in the sensor inner cavity, and a first needle-shaped working electrode (2), a second needle-shaped working electrode (4) and a reference electrode (3) are fixed on the bottom surface of the base (1); the fixed ends of the first needle-shaped working electrode (2), the second needle-shaped working electrode (4) and the reference electrode (3) are respectively connected with corresponding signal contacts on a printed circuit board (6) through different conducting strips (5), and the tips of the first needle-shaped working electrode (2), the second needle-shaped working electrode (4) and the reference electrode (3) all protrude out of the bottom surface of the base (1); the first needle-shaped working electrode (2), the second needle-shaped working electrode (4) and the reference electrode (3) form a double-electrode system respectively;
the first needle-shaped working electrode (2) is of a multilayer composite structure, a first metal needle core (2.1) is arranged at the center, and a first catalytic metal layer (2.2) and a first biocompatible polymer permeation film layer (2.3) are sequentially wrapped outside the first metal needle core (2.1);
the second needle-shaped working electrode (4) is of a multilayer composite structure, a second metal needle core (4.1) is arranged at the center, and a second catalytic metal layer (4.2), a tyrosinase layer (4.3) and a second biocompatible polymer permeation membrane layer (4.4) are sequentially wrapped outside the second metal needle core (4.1).
2. The sensor for minimally invasive detection of levodopa according to claim 1, wherein the first metal stylet (2.1) and/or the second metal stylet (4.1) is made of gold.
3. The minimally invasive sensor for detecting levodopa according to claim 1, wherein the first catalytic metal layer (2.2) and/or the second catalytic metal layer (4.2) are gold nanoparticles.
4. The sensor for minimally invasive detection of levodopa according to claim 1, characterized in that the first biocompatible polymer permeable membrane layer (2.3) and/or the second biocompatible polymer permeable membrane layer (4.4) is a polyurethane layer.
5. The sensor for minimally invasive detection of levodopa according to claim 1, wherein said reference electrode (3) is a silver/silver chloride electrode.
6. The sensor for minimally invasive detection of levodopa according to claim 1, wherein a circle of adhesive tape is attached to an edge portion of the bottom surface of the base (1) for adhesively fixing the sensor to the skin surface.
7. The sensor for minimally invasive detection of levodopa according to claim 1, wherein the first needle-shaped working electrode (2), the second needle-shaped working electrode (4) and the reference electrode (3) are detachably fixed to the base (1).
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| Application Number | Priority Date | Filing Date | Title |
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| CN202020511116.2U CN212546944U (en) | 2020-04-09 | 2020-04-09 | A sensor for minimally invasive detection of levodopa |
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| CN202020511116.2U CN212546944U (en) | 2020-04-09 | 2020-04-09 | A sensor for minimally invasive detection of levodopa |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111387993A (en) * | 2020-04-09 | 2020-07-10 | 浙江大学 | Sensor and detection system for minimally invasive detection of levodopa |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111387993A (en) * | 2020-04-09 | 2020-07-10 | 浙江大学 | Sensor and detection system for minimally invasive detection of levodopa |
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