Kai Fan, Kuei-Lin Liu, Jun-Hsuan Chung, Zong-Hong Lin
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There is an immense urgency to develop a sensing platform that can detect the essential ions as well as biomarkers from the interstitial fluid (ISF) as it contains valuable information about the physiological status of a person. According to Centers for Disease Control and Prevention (CDC), imbalance of sodium concentration in the body may lead to stroke, hypertension, and epilepsy; for potassium: arrhythmia, chronic kidney disease (CKD), and dizziness; for calcium: depression, osteoporosis, and other bone-related disease; for pH of body fluid: urinary tract infection, respiratory acidosis, and sleep apnea. Within this advent of wearables, microneedle (MN)-based transdermal sensors are well positioned to play a key role in combining the significant benefits of dermal interstitial fluid (ISF) as a source of clinical indicators and minimally invasive skin puncturing to allow the collection of real-time diagnostic data. In this context, we have developed a MNs based versatile platform for the transdermal amperometric detection of glucose and different clinically relevant biomarkers such as K + , Na + , Ca 2+ in the body fluid in a robust, reliable, and cost-effective way. Here, stainless steel microneedle (SS-MN) is used as an ideal candidate for multiplex sensing due to its great chemical stability as well as the rigidity for accurate and painless puncture. The device is fabricated with ion selective electrode (ISM) coating on each needle for their corresponding electrolyte and enzyme for glucose detection. In vitro experiments performed in artificial ISF samples yielded excellent sensitivity and a good linear response. The sensor is successfully applied for in vivo detection of glucose and these ions in SD rats for validating their feasibility as a real-time sensing device. 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According to Centers for Disease Control and Prevention (CDC), imbalance of sodium concentration in the body may lead to stroke, hypertension, and epilepsy; for potassium: arrhythmia, chronic kidney disease (CKD), and dizziness; for calcium: depression, osteoporosis, and other bone-related disease; for pH of body fluid: urinary tract infection, respiratory acidosis, and sleep apnea. Within this advent of wearables, microneedle (MN)-based transdermal sensors are well positioned to play a key role in combining the significant benefits of dermal interstitial fluid (ISF) as a source of clinical indicators and minimally invasive skin puncturing to allow the collection of real-time diagnostic data. In this context, we have developed a MNs based versatile platform for the transdermal amperometric detection of glucose and different clinically relevant biomarkers such as K + , Na + , Ca 2+ in the body fluid in a robust, reliable, and cost-effective way. Here, stainless steel microneedle (SS-MN) is used as an ideal candidate for multiplex sensing due to its great chemical stability as well as the rigidity for accurate and painless puncture. The device is fabricated with ion selective electrode (ISM) coating on each needle for their corresponding electrolyte and enzyme for glucose detection. In vitro experiments performed in artificial ISF samples yielded excellent sensitivity and a good linear response. The sensor is successfully applied for in vivo detection of glucose and these ions in SD rats for validating their feasibility as a real-time sensing device. 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引用次数: 0
摘要
由于全球人口老龄化和物联网(IoT)的普及,可穿戴设备技术在医疗保健领域发挥着巨大的作用。此外,2019冠状病毒病(COVID-19)大流行加速了可穿戴医疗设备在市场上的出现。慢性疾病患者更关注体内单一或多种营养物质和生物标志物的追踪。糖尿病是一种典型的慢性疾病,患者需要长期监测血糖水平。此外,糖尿病患者还面临电解质失衡,从而引发其他几种疾病。由于间质液(ISF)包含有关人的生理状态的宝贵信息,因此开发一种能够检测必需离子和生物标志物的传感平台迫在眉睫。根据疾病控制和预防中心(CDC),体内钠浓度失衡可能导致中风、高血压和癫痫;对于钾:心律失常、慢性肾病(CKD)和头晕;补钙:抑郁症、骨质疏松症和其他骨相关疾病;体液pH值:尿路感染,呼吸性酸中毒,睡眠呼吸暂停。随着可穿戴设备的出现,基于微针(MN)的透皮传感器将发挥关键作用,将真皮间质液(ISF)作为临床指标来源的显著优势与微创皮肤穿刺相结合,以收集实时诊断数据。在此背景下,我们开发了一种基于MNs的多功能平台,用于透皮安培检测葡萄糖和体液中不同临床相关的生物标志物,如K +, Na +, ca2 +,这是一种稳健,可靠和经济有效的方法。在这里,不锈钢微针(SS-MN)被用作多路传感的理想候选者,因为它具有很强的化学稳定性以及精确和无痛穿刺的刚性。该装置在每个针头上涂有离子选择电极(ISM),用于检测相应的电解质和葡萄糖酶。体外实验在人工ISF样品中进行,获得了极好的灵敏度和良好的线性响应。该传感器成功应用于SD大鼠体内葡萄糖及这些离子的检测,验证了其作为实时传感装置的可行性。总的来说,这一发展的概念包括与人体电解质失衡相关的葡萄糖和其他离子的传感方面的重大进展,这与控制几种疾病有关。
Development of Wearable Microneedle-Based Platform for Real-Time Biomarkers Sensing
The wearable device technology plays a huge role in the healthcare sector owing to the aging global population and increased acquisition of the internet of things (IoT). Further, the Coronavirus Disease-2019 (COVID-19) pandemic has accelerated the emergence of wearable medical devices in the market. The patients with chronic diseases are more focused on tracking single or multiple nutrients and biomarkers in the body. Diabetes is a classic example of chronic disease where the patients need to monitor their blood glucose level for a long time. In addition, diabetic patients also face electrolyte imbalance which gives rise to several other diseases. There is an immense urgency to develop a sensing platform that can detect the essential ions as well as biomarkers from the interstitial fluid (ISF) as it contains valuable information about the physiological status of a person. According to Centers for Disease Control and Prevention (CDC), imbalance of sodium concentration in the body may lead to stroke, hypertension, and epilepsy; for potassium: arrhythmia, chronic kidney disease (CKD), and dizziness; for calcium: depression, osteoporosis, and other bone-related disease; for pH of body fluid: urinary tract infection, respiratory acidosis, and sleep apnea. Within this advent of wearables, microneedle (MN)-based transdermal sensors are well positioned to play a key role in combining the significant benefits of dermal interstitial fluid (ISF) as a source of clinical indicators and minimally invasive skin puncturing to allow the collection of real-time diagnostic data. In this context, we have developed a MNs based versatile platform for the transdermal amperometric detection of glucose and different clinically relevant biomarkers such as K + , Na + , Ca 2+ in the body fluid in a robust, reliable, and cost-effective way. Here, stainless steel microneedle (SS-MN) is used as an ideal candidate for multiplex sensing due to its great chemical stability as well as the rigidity for accurate and painless puncture. The device is fabricated with ion selective electrode (ISM) coating on each needle for their corresponding electrolyte and enzyme for glucose detection. In vitro experiments performed in artificial ISF samples yielded excellent sensitivity and a good linear response. The sensor is successfully applied for in vivo detection of glucose and these ions in SD rats for validating their feasibility as a real-time sensing device. Overall, this developed concept comprises of significant progress in the sensing of glucose and other ions in relation to an electrolyte imbalance in the humans that holds relevance in controlling several diseases.