KR-20260065428-A - Biosensor for Transdermal type noninvasive continuous glucose measurement system

Abstract

The present invention relates to a biosensor structure and compositional material used for continuous glucose measurement by a non-invasive method of extracting human interstitial fluid glucose through the application of micro-direct current to skin tissue.

Inventors

• 이동훈
• 박명성

Assignees

• (주) 테크포엠

Dates

Publication Date

20260508

Application Date

20241101

Claims (6)

1. Electrolyte gel of a transdermal, non-invasive continuous glucose monitoring biosensor composed of 0.5% - 2.5wt% sodium alginate and glucose oxidase
2. The solvent of claim 1 is a physiological saline solution (phosphate buffer solution) with a 1/2 concentration in the pH range of 5.8 to 7.0.
3. Extraction of sugar molecules into skin tissue; the magnitude of the micro-DC current is possible by adjusting the pH of the electrolyte gel.
4. The signal magnitude and analysis time of sugar molecules extracted from skin tissue using micro-DC current can be controlled by the area ratio of the working electrode and the counter electrode.
5. The two extraction electrodes for extracting sugar molecules from skin tissue are carbon-component electrodes, and the working electrode and counter electrode materials are composed of carbon electrode materials containing 5-25 wt% platinum.
6. Sugar molecules within skin tissue can be extracted by applying a direct current of 0.100 mA or less.

Description

Transdermal noninvasive continuous glucose measurement biosensor The present invention relates to a biosensor configuration and constituent materials used in a transdermal, non-invasive continuous glucose monitor capable of repeated use. The Continuous Glucose Monitoring System (CGMS) was developed to overcome the inconvenience of the method of measuring human glucose levels sporadically by extracting blood using a lancet. Since the onset times of hypoglycemia and hyperglycemia symptoms in diabetic patients are not fixed, wearing a CGMS allows for the regular measurement of blood glucose levels at set intervals, making it possible to alert patients to risks they may not be aware of. Continuous glucose monitors are classified into invasive and non-invasive types. The micro-needle method involves inserting a penetrating micro-needle into the human skin tissue to induce interstitial fluidal glucose into a biosensor at regular intervals, which is then analyzed to continuously measure the body's glucose concentration. This method has recently begun to be used as a medical device because it offers higher reliability when compared to glucose concentration readings obtained through blood sampling. Currently, such products are being manufactured by medical device companies including Korea's i-Sens and the U.S.'s Dexcom and Abbott, while other multinational medical companies are preparing to launch their own products. Non-invasive methods can overcome the disadvantages of invasive continuous glucose monitors by not inserting a needle into the skin. Although methods for analyzing glucose concentration have been proposed primarily through electro-physical signals or physiological signals generated by the human body and optical measurements through the skin, they are not used as medical devices in the field of glucose measurement because their reliability is low and inaccurate measurement results pose a risk to the user. Among non-invasive methods, the electro-reverse ionosmosis method is suitable for use as a medical device. This method involves applying a micro-direct current to the skin for a certain period to induce interstitial fluid glucose within the epithelial tissue to a biosensor in a non-invasive manner. Existing transdermal biosensors using the electroosmosis method have faced difficulties in reproducibly measuring glucose concentrations due to severe signal distortion at the biosensor's analysis electrode. This is because the immobilization of glucose oxidase (GOD) to the electrolyte molecular ring is irregular, making it difficult for glucose molecules to react with GOD, and thus causing significant signal reduction. Furthermore, commercialization has been difficult due to the disadvantage that the mobility of human glucose molecules induced by the direct current within the skin tissue is affected by the degree of crosslinking during the synthesis of materials such as HPMA polymer gels used as electrolytes. This results in molecules failing to reach the biosensor's glucose analysis electrode, causing a decrease in signal. Additionally, the sensitivity to the shape and composition of the electrode has made it difficult to achieve a high level of completeness in the construction of the non-invasive biosensor. Therefore, in order to commercialize the biosensor for a transdermal non-invasive continuous glucose monitor, it is necessary to improve the electrolyte, the structure of the electrode, and the characteristics of the biosensor based on the electrode structure. Figure 1 shows the structure and principle of a transdermal non-invasive continuous glucose meter. Figure 2 shows the structure of a transdermal non-invasive continuous glucose monitor biosensor. Figure 3 shows continuous glucose monitoring signals obtained from forearm skin tissue at 20-minute intervals, including 2-minute glucose molecule extraction, using a transdermal non-invasive continuous glucose monitoring biosensor. Figure 4 shows a comparison between the measured signal value (nA) of a transdermal non-invasive continuous glucose monitoring biosensor and the blood glucose value (mg/dl) obtained from a blood glucose meter. The term “noninvasive” as used in this specification refers to the extraction of (interstitial fluid sugar, glucose, glucose) having characteristics similar to blood sugar concentration within skin tissue using a micro-direct current without making a hole in the skin, which is induced into a biosensor. As used in this specification, “glucose oxidase (GOD)” refers to a substance that selectively reacts with interstitial fluid sugars extracted from skin tissue to oxidize them, releasing two electrons to form hydrogen peroxide and gluconic acid, which generate a signal. The “electrolyte” used in this specification refers to a gel that maintains its shape without becoming a low-viscosity fluid due to body temperature and does not cause skin irritation, and which lowers skin resistance by increasing the adhesion between the s