耐用型植入式葡萄糖生物感測器

耐用型植入式葡萄糖感測器具有至少兩周的壽命，在連續血糖監測（CGM）和為新出現的糖尿病患者開發閉環人工胰腺系統中發揮關鍵作用。這篇簡短的綜述總結了 CGM 系統的現有技術，並指出了電流型葡萄糖生物感測器關於其固有感測器耐用性和信號穩定性的具體局限性，這些感測器耐用性和信號穩定性主要是由感測器植入後不可避免的異物反應引起的。

Abstract - 摘要

Long-term implantable glucose sensors with a demonstrated lifetime of at least two weeks play a key role in continuous glucose monitoring (CGM) and the development of closed-loop artificial pancreas systems for the emerging number of diabetes patients. This short review summarises the current state of the art of CGM systems and points out specific limitations of amperometric glucose biosensors regarding their inherent sensor long-term and signal stability that are mainly caused by the inevitable foreign body response after sensor implantation.

Figure - 圖片

Figure 1. Comparison of typical reaction cycles in a chemical batch reactor (A) and in a simplified scheme of a glucose converting redox enzyme (B). Left: description of a four-step cycle passed through on the level of a single batch reaction (1-4) and a single enzymatic conversion (I–IV), respectively. Right: integration of single reactors/enzymes picture into the scale of (A) a production plant where several batch reactors are in different states and substrate needs to be delivered as well as product is picked up. In (B) a model of an electrochemical biosensor with glucose converting enzymes immobilised inside a redox hydrogel matrix is shown. The enzymes are randomly oriented and substrate has to diffuse towards their active centres before the conversion and turnover current generation can take place.

Figure 2. Radar chart comparing the currently available CGM systems in five different categories. The maximum achievable values for each category were specifically defined and each system"s rating was adjusted to an individual scale: Lifetime, 90 days (～3 months); Accuracy, MARD 0% with a cut off at 15%; Calibration interval, factory calibrated sensors with maximum rating (100). All others dependent on average number of hours between two calibrations; Communication, platform independent connection to smartphones/watches accompanied by easy data handling and sharing justifies maximum rating, each restriction leads to deduction of points; Special features, integration/combination with insulin pumps or insulin reservoirs and other features like a vibration alert summed up for each device.

Figure 3. Foreign body response to an implanted sensor. Initial tissue damage, caused by the implantation procedure, inevitably triggers a host response. Proteins get attached to the sensor and facilitate the adhesion of cells, such as neutrophils, macrophages and lymphocytes. After acute tissue inflammation, a fibrous capsule forms around the implanted sensor.

Figure 4. Schematics of an enzymatic sensor based on substrate consumption (left) and a polymer-based affinity sensor (right) showing the concentration profiles of glucose in front of the transducer surface. Due to the catalysed substrate turnover, the enzymatic sensor shows a depletion of the glucose concentration towards the electrode surface varying with respect to the activity of the enzymes which are immobilised inside the redox polymer matrix. The affinity sensor is under permanent equilibrium conditions. Thus, no glucose concentration gradient occurs and only equilibrium perturbations are detected until a new equilibrium state is attained once the glucose concentration varies.

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