闫晗 刘丽妍 李至洁 罗丹 刘皓
摘要:可穿戴传感器以独特的监测模式(实时、连续、非侵入性)在医疗、体育、健康监测等领域得到了迅速发展。汗液中含有多种生物标记物,如代谢物、电解质和各种激素等。汗液可以反映人体的劳累程度、疾病、压力水平、运动情况等,与可穿戴技术相结合,汗液传感器有望实现低成本、实时、原位的汗液监测。本文从柔性汗液传感器的基底材料种类入手,介绍了近年来汗液传感器常用的基底材料,并概述了柔性汗液传感器在监测方面的应用。最后,总结了目前存在的局限性及对未来发展的展望。
关键词:汗液;传感器;柔性;智能可穿戴;健康监测;应用
中图分类号:TP212.6; TS101.8
文献标志码:A
文章编号:10017003(2024)02008510
DOI:10.3969/j.issn.1001-7003.2024.02.010
收稿日期:20230825;
修回日期:20231216
基金项目:科技部国家重点研发计划“科技冬奥”重点专项项目(2019YFF0302105);国家自然科学基金项目(51473122);中国博士后科学基金项目(2016M591390);天津市自然科学基金项目(18JCYBJC18500)
作者简介:闫晗(1998),女,硕士研究生,研究方向为柔性智能传感器方面的研究。通信作者:刘皓,教授,liuhao_0760@163.com。
随着电子设备技术的快速发展,各种各样的柔性可穿戴传感器已经逐渐进入人们的生活,柔性可穿戴传感器在医疗、军事、教育上具有极为重要的地位和应用潜力。同时,伴随着人们对健康监测的日益重视,可结合个人情况定制的个性化可穿戴设备引起了人们的广泛关注,柔性传感是健康监测设备中最有前途的技术之一。目前,大多数可穿戴设备主要用于监测人的身体状况的变化(如心率、运动、温度等),在反映人体整体健康状况方面存在局限性。因此,实时监测体液、血液和间质液等生物体液进行生理健康評估已成为可穿戴传感器发展的新趋势。与血液成分的有创分析相比,无创的体液监测(如泪液、唾液、汗液)是一种更方便、简单、安全的获取生理信号的方法。与泪液、唾液和尿液等其他生物体液取样的复杂性和不适性相比,汗液的取样可以无创地按需获取,甚至可以被连续采集。汗液取样可以方便且不显眼地实现采集,从而体现出可穿戴式传感器在体液监测方面具有的巨大潜力。
汗液是人体汗腺分泌的液体,分布在身体的各个部位,同时汗液也是调节核心体温的重要体液之一。汗液由电解
质离子、代谢物、重金属、小分子等多种成分组成。这些汗液成分包含丰富的人体健康信息,一些重要的诊断可以通过汗液生物标志物来实现,如代谢活动、糖尿病、脱水状态和囊性纤维化。同时,汗液还能监测人们不同状态下的情绪。时常加班的人群精神压力有时候会很大,情绪会有不同程度的起伏,长期静息状态下的汗液监测可以察觉到人们的心理压力导致的汗液分泌,从而可以做出一定调整,如增加减压训练、配备心理辅导等,避免发生意外。所以可以说汗液是体外监测的最佳监测物质。
当前关于柔性可穿戴汗液传感器的研究,主要从监测物质、监测方法和监测原理等方面展开讨论,而从基底材料角度入手分析的文章在国内外比较少。基于此,本文首先介绍近年来汗液传感器常用的基底材料;其次,概述柔性汗液传感器在监测方面的应用;最后,总结目前存在的局限性及对未来发展的展望。
1 柔性汗液传感器的基底材料
柔性可穿戴电子设备需要匹配人体皮肤的弯曲和拉伸且不影响佩戴者日常活动。由于传统的可穿戴传感器大多数基底都是刚性的,无法满足人们的可穿戴使用,因此柔性基底材料的研究成为现阶段柔性传感器领域的重点。本文对常用于柔性汗液传感器的基底材料进行了分类,主要分为薄膜基底材料、纺织基底材料和纸基底材料,具体特点如表1所示,具体类型如图1所示。
1.1 薄膜基底材料
1.1.1 聚对苯二甲酸乙二醇酯
聚对苯二甲酸乙二醇酯(PET)是全球最常见且用途广泛的一种高分子热塑性材料,因其具有较高的化学惰性、环境稳定性、电绝缘性和重量轻等特点,常被当作基底材料,用于柔性传感器中。
Mei等开发了一种基于纳米纤维微流控技术和分子印迹聚合物(MIP)的柔性电化学传感器,用于原位和实时汗液分析。以PET为基底的传感器由两层组成,底层是用于传感的MIP修饰电极层,上层是用于自发排汗的纳米纤维微流控层,是利用静电纺丝技术,制备了由聚酰亚胺/十二烷基硫酸钠组成的纳米纤维膜。该传感器以皮质醇为模型分析物,表现出1 nM~1 μM的宽检测范围及优异的选择性和稳定性。Chen等开发了一种灵敏、小型化、灵活的电化学汗液pH值传感器,用于连续实时监测人体汗液中的氢离子浓度。将氟烷基硅烷功能化的TiCT(F-TiCT)与聚苯胺(PANI)膜相结合,采用简单、低成本的丝网印刷技术在PET基底上制备柔性电极,取代了传统的离子敏感膜。构建的微型便携式可穿戴pH值传感器旨在实时监测运动过程中人体汗液的pH值。对女性和男性志愿者进行体表汗液pH值监测,该传感器具有较高的准确性和连续稳定性。Cui等开发了一种可穿戴的电化学传感器,用于监测汗液中的pH值和K。该传感器是使用微电子打印机在PET基底上印刷β-CD功能化石墨烯(β-CD/RGO)悬浮液制成的。其在不同弯曲状态下均表现出良好的电位稳定性,与非原位分析相比,体表汗液pH值和K测量显示出较高的准确性。Francesca等以氧化铟锡包覆的PET为柔性衬底,制备一种基于聚苯胺的可穿戴pH值电化学传感器。在恒电位下沉积聚苯胺膜,为了提高传感器的性能,使用还原氧化石墨烯修饰成双层电极。该传感器表现出良好的性能,灵敏度为62.3 mV/pH,非常接近能斯特响应,重复性为3.8%,可用于测定pH值在2~8的生物体液。
1.1.2 聚酰亚胺
聚酰亚胺(PI)具有耐高温和极低温、高柔韧性和机械强度,以及高效隔热等优异性能。作为基底材料,其具有较好的绝缘性、耐热性和吸湿性,同时对化学药品也具有一定的抗腐蚀性,在柔性电子领域展现出广阔的应用前景。
Liao等通过在PI薄膜上使用激光诱导石墨烯(LIG)技术制造了一种可穿戴式表皮传感器,用于多路汗液分析。该LIG装置可以同时监测汗液中的pH值、Na和K水平,灵敏度分别为51.5 mV/dec(pH值)、45.4 mV/dec(Na)和43.3 mV/dec(K),在弯曲状态下保持了良好的传感性能,还具有良好的重复性、稳定性和选择性。Barber等研究了激光诱导改性PI基底制备对溶液pH值敏感的导电石墨化轨道的方法。使用电位法和伏安法研究了几种传感器形式,电位测量系统显示该传感器具有能斯特响应,采用核黄素(维生素B)氧化还原探针的伏安测量系统能够分析出该传感器的能斯特曲线(56 mV/pH)。Sun等研制了一种柔性可穿戴的生物传感器,用于人体皮肤表面汗液中葡萄糖的实时监测。利用激光诱导PI薄膜合成了LIG,制成了叉指电极(IEs)。此外,通过热还原氧化石墨烯(GO)合成了IEs表面修饰的半导体rGO传感膜,并通过化学交联与葡萄糖氧化酶(GOx)进行功能化,获得GOx/FWCB。该传感器可用于0.01~3.0 mM内葡萄糖的测定,具有较好的选择性,检出限为0.8 μM(S/N=3),满足了快速、无损检测葡萄糖的要求。
1.1.3 聚二甲基硅氧烷
聚二甲基硅氧烷(PDMS)是一种生物相容性好、化学性质稳定的高分子聚合物,同时具有优异的拉伸性、弯曲性和可压缩性,可作为柔性基底材料,广泛应用于可穿戴传感器中,特别是在制备应变需求强和环境复杂的传感器中有显著优势。
Bae等报告了一种可拉伸的微流体葡萄糖传感器。在应力吸收及三维微图案化的PDMS基底上制备了高度电催化的纳米多孔金电极,在非酶葡萄糖检测中呈现机械拉伸性、高灵敏度和耐用性的特点。通过将可拉伸棉织物作为毛细管,嵌入到薄的聚氨酯纳米纤维中来增强PDMS通道,制成了一种薄的、可拉伸的、坚韧的微流体装置。该设备能够收集皮肤中的汗液,并将其准确地传输到电极表面,因此具有出色的监测汗液中葡萄糖水平的能力。Shu等制备了一种基于PDMS薄膜的高性能可穿戴电化学传感器,用于连续监测汗液中的葡萄糖。通过化学沉积法在PDMS薄膜基底上沉积一层金,可制备柔性的Au/PDMS薄膜电极。该传感器对葡萄糖的测定具有良好的电化学性能,线性范围为20 μM~790 μM,灵敏度为205.1 μA/mm/cm。此外,传感器在400次重复拉伸/释放、拉伸和弯曲到不同程度后仍表现出高的机械性和电化学稳定性。它还可用于血糖的长期监测,15 d内保持98%的原值。Yun等通过在自组装纳米片(AuNS)上逐层沉积真空过滤法制备的碳纳米管(CNT)薄膜,在PDMS可伸缩基底上制备了可伸展电极。随后,采用水热合成法分别制备了CoWO/CNT和聚苯胺/CNT复合材料,并将其涂覆在CNT-AuNS电极上,成功地制作出一种用于检测汗液中葡萄糖和pH值的电化学传感器。该传感器对湿润皮肤具有良好的黏附性,葡萄糖和pH值的灵敏度分别为10.89 μA/mM/cm和71.44 mV/pH。它不受汗液中其他离子和化学成分的干扰,在空气中能保持长期稳定性(约10 d),且经过1 000次反复拉伸和释放,机械稳定性仍达到30%。
1.2 纺织基底材料
纺织基主要以纤维、纱线和织物的形式作为基底材料,多用于制备传感器。由于纺织基具有透气性、柔韧性、舒适性、质量轻和成本低等优秀的特性,被视为有前途的基底材料。相对于其他基底材料制备的柔性汗液传感器来说,基于纺织品的汗液传感器有着优秀的传感性能和舒适性,能够广泛应用到可穿戴领域。
Zhao等通過一种基于弹性金纤维的三电极电化学平台,制备了可穿戴纺织品葡萄糖生物传感器。用普鲁士蓝和葡萄糖氧化酶对金纤维进行功能化处理,得到工作电极;用Ag/AgCl修饰作为参比电极,未经改性的金纤维作为对电极,制备出传感器的灵敏度为11.7 μA/mM/cm。即使在拉伸率达到200%的情况下,它的传感性能也保持稳定。Wang等使用金纤维制备了乳酸生物传感器,并进一步编织成具有平面布局的标准三电极体系的纺织品。此传感器在人工汗液中灵敏度为14.6 μA/mM/cm,同时灵敏度可以在高拉伸应变下仍保持100%。
Zhang等开发了一种基于全织物的双功能柔性可穿戴式汗液电化学传感器,该传感器以织物为基底,实现了汗液的定向输送和多组分综合检测的双重功能。通过Janus织物获得高效集汗,可以有效地将汗液从皮肤一侧转移到电极上,实现微量采集。该传感器可以实现良好的传感性能和高效的集汗双重功能,并且具有良好的灵活性和佩戴的舒适性。Mugo等通过叠层组装(LbL)在柔性棉织物基底上制备可穿戴式皮质醇传感器。其具有良好的精度,对9.8~49.5 ng/mL的皮质醇响应迅速(<2 min),在动态范围的平均相对标准偏差为6.4%;且皮质醇传感器的检测下限为8.00 ng/mL,符合人体汗液的生理水平;同时单个皮质醇传感器贴片可以在30 d内重复使用15次,没有性能损失,也证明了其出色的可重用性。Singh等制作了一种基于棉织物的可穿戴传感器,用于实时葡萄糖监测。其制造分两步进行,一是在棉织物上聚合吡咯以使其导电;二是在导电棉织物上沉积Cu-Mn。研究表明该传感器可靠,葡萄糖检出限和定量限分别为125 μM和378 μM。Ma等通过在棉织物上丝网印刷炭黑和再生丝胶,制备了一种基于纺织品的汗液传感器。获得的织物具有优异的柔韧性、良好的亲水性(接触角为86°)和适当的电阻率(61.7 Ω/cm),可用作可穿戴式汗液传感器的工作电极。可穿戴式汗液传感器具有高灵敏度(在酸性汗液中电阻变化率为42.7%)、柔韧性和可洗涤性(洗涤30次后仍保持99.1%)。
Mo等采用一种简单而新颖的电助纺芯技术(EACST),开发了一种基于皮芯结构传感纱的电化学织物传感器,用于原位监测人体汗液中的钾离子浓度。诱导纱表皮层纳米纤维表现出优异的亲水性和较高的比表面积(8.85 m/g),织物经、纬纱亲疏水性差异显著。因此,可以在皮肤传感区域实现汗液极限域的吸收,从而使传感器在短时间内(2.1s)快速响应并实现长期稳定传感(6 000 s以上)。此外,该传感器具有优异的选择性,潜在的再现性及低噪声和信号漂移(3.6×10 mV/s)。该传感器还可以缝制到衣服上,有效地收集汗液,实时现场监测人体汗液中的K信号。
1.3 纸基底材料
在可穿戴式汗液传感器中,以纸基作为基底的纸质汗液传感器因其成本低、制作简单、检测时间短、采样方便等优点而备受关注。此外,基于纸基的传感器能过滤一些可能影响汗液传感器检测性能的不必要的干扰,即液体中的颗粒物质和灰尘。
Yang等提出了一种过滤汗液中皮脂的纸质三明治结构pH值传感器。该传感器可以过滤汗液中90%以上的皮脂,也可以监测人体代谢水平和身体pH值平衡,人体试验进一步证实了纸质三明治结构传感器的可行性。Al-Hardan等介绍了一种低成本且操作简单制备pH值传感器的方法,使用羊皮纸作为基底、铅笔迹线作为电极来制备pH值传感器。羊皮纸的疏水性延长了pH值传感器的使用寿命。发明的传感器具有能斯特响应,其灵敏度为(52.1±1.5)mV/pH,在pH值 4~10的线性度为0.995。Li等报告了一种低成本、独立式、一次性的高集成传感纸(HIS纸),将HIS纸折叠成多层结构,制备了能同时检测葡萄糖和乳酸的双通道电化学传感器,其灵敏度分别为2.4 nA/μM和0.49 nA/mM。该方法为可穿戴生物电子在内的一系列生化平台提供了一种小型化、低成本且灵活的解决方案。
2 柔性汗液传感器的应用
汗液中的组分含量可以反映人体的生理状况,常见的监测物质及有关信息如表2所示。在身体异常状况下,汗液中的物质成分浓度会发生变化,如汗液中的血糖浓度变化通常会导致糖尿病或低血糖。同时,监测汗液的方法主要包括电化学、比色法等在内的多种方法进行监测,这些不同类型的监测方法可以应用在不同成本范围和不同应用环境下,为柔性汗液传感器在运动和静息、治疗和预防、疾病和保健等多种条件和目的下提供充足的备选。
2.1 用于监测电解质离子的柔性汗液传感器
电解质浓度异常可导致酸中毒、肾功能衰竭等高发病率和高死亡率疾病的发生,而人体出汗率和电解质浓度密切相关,因此实时监测汗液中的电解质浓度和酸碱参数对人体健康预警特别重要。汗液中含有大量的Na、K、Cl、Ca、H等多种无机电解质离子,使汗液具有天然、安全、可靠的电解质特性。这些离子与人类的心率、血压、心血管功能、肌肉收缩、酶激活和骨骼发育密切相关。通过分析特定电解质离子的浓度,可以达到早期诊断疾病的目的。
pH值和H浓度相关,主要用于维持人体pH值平衡。pH值是诊断疾病的关键指标,正常人体汗液的pH值约为3~8,但大多数情况约为弱酸性。然而,pH值的不正常波动会出现一些健康问题,如皮炎和真菌感染。因此pH值对健康起着重要作用,且汗液pH值与人体的水合状态有关,是囊性纤维化等疾病状诊断的重要指标。Hou等通过选择合适的溶剂和静电纺丝条件,将聚苯胺(PANI)和聚氨酯(PU)通过同轴静电纺丝技术结合,成功研制出PANI//PU核壳纳米纤维柔性pH汗液传感器。该传感器在pH 2~7内与pH值呈线性关系,灵敏度为-60 mV/pH且可以检测到低于pH 0.2的变化,可用于汗液pH值的灵敏检测。Ha等提出了基于姜黄素和热塑性聚氨酯(C-TPU)电纺纤维的可穿戴比色汗液pH值传感器,通过监测汗液pH值来诊断疾病状态。该传感器通过改变颜色来响应从烯醇到二酮形式的化学结构变化,从而帮助监测pH值。此外,传感器通过恢复姜黄素的烯醇形式而具有可逆的pH值比色传感性能,从而可诊断服装具有耐用性和可重复使用性。这项研究有助于為需要持续汗液pH监测的囊性纤维化患者开发智能诊断服装。
Cl是人体汗液中含量最丰富的电解质,测量其浓度可提供人体电解质平衡的最佳指标,也可用于诊断和预防中暑。Shitanda等制作了一种用于实时监测汗液的新型氯离子传感器。打印的传感器被热转移到非织造布上,从而可以轻松地附着在各种类型的衣服上。这种布料还可以防止皮肤和传感器之间的接触,并起到流动通道的作用。氯离子传感器的电动势变化量为-59.5 mTV/log C,且传感器与人体汗液中氯离子浓度范围呈良好的线性关系。此外,该传感器还结合了无线发射器,可以无线监测汗液中的离子,适用于监测长期在高温状态下工作的人群,如工人、外卖员、户外执勤民警等。
汗液中Na浓度的变化可以作为监测长期运动过程中脱水的生物标志物,这对运动员的水摄入量有重要意义。通过这种方式,可以预防因大量出汗而导致的水和电解质缺乏。同时Na浓度的变化还可以监测热应激,检测各种疾病,如低钠血症和囊性纤维化,为临床诊断提供重要信息。K在神经和肌肉细胞功能、细胞生化反应和碳水化合物代谢中起重要作用。Mazzaracchio等制备了基于炭黑纳米材料的丝网印刷电化学传感器。对Na的检测范围为10 M~1 M,灵敏度为(58±3)mV/dec,检出限为63 μM,这可以用来检测实际汗液样品中的钠离子含量。Pirovano等使用聚(3,4-乙烯二氧噻吩)(PEDOT)和聚(3-辛基噻吩-2,5-二基)(POT)作为导电聚合物,并使用固体离子敏感电极(ISEs)来制备监测汗液的可穿戴傳感器。测试表明,PEDOT对钠离子和钾离子的灵敏度分别为(52.4±6.3)mV/dec和(45.7±7.4)mV/dec。POT对钠离子和钾离子的灵敏度分别为(56.4±2.2)mV/dec和(54.3±1.5)mV/dec。此外,运动员的骑行试验表明,90 min内Na浓度的动态范围为1.89~2.97 mm,K浓度的动态范围为3.31~7.25 mm,可以用来测定高水平运动员汗液中的电解质。Alizadeh等研制了一种无线可穿戴汗液传感装置,适用于中等强度运动中电解质的连续监测,并可作为水合状态的测量标准。Na和K的灵敏度分别为55.7 mV/dec和53.9 mV/dec,通过预测分析,该装置可用于监测高强度排汗过程中的电解质,适用于监测运动员和健身爱好者。
2.2 用于监测代谢物的柔性汗液传感器
乳酸积累会引起身体的酸痛和疲劳,长期积累会导致身体酸化或乳酸酸中毒等严重疾病,严重时可导致失血性休克。因此,检测乳酸可以反映氧化代谢不足和组织损伤,用于预防运动中肌肉酸痛、疼痛和痉挛,并为缺血提供早期预警。
Zhang等利用丝网印刷技术,在PET的柔性基底上构建了一种基于银纳米线(AgNW)的表皮电化学生物传感器(MIPs-AgNWS),用于人体运动汗液中乳酸的无创监测。该传感器在200次弯曲和扭转循环后表现出稳定的电化学响应。乳酸的监测范围为10 M~0.1 M,检测下限为0.22 μM。该传感器在室温和黑暗条件下存放7个月后,灵敏度保持在99.8%±1.7%,有利于运动员的保健和生理监测。Wang等研究合成ZIF-67衍生的NiCo层状氢氧化物(NiCo LDH),作为非酶乳酸检测的电催化剂,成功制备了无酶乳酸生物传感器。NiCo-LDH具有均匀的孔隙率,较大的比表面积和层次化的层状结构。在乳酸浓度为2~26 mM内,传感器灵敏度达到83.98 μA/mM/cm。因此,该传感器可以实现人体汗液中乳酸的无创监测,这在无氧运动和有氧运动中都具有重要意义。
血糖浓度是衡量患者健康状况的关键指标。由于汗液中葡萄糖水平与血糖浓度相关,因此可以利用可穿戴汗液传感器实时监测汗液中葡萄糖水平,从而反映患者的健康状况。
Wang等通过在金电极上浇铸普鲁士蓝和葡萄糖氧化酶,成功制备了基于PET的葡萄糖传感器。该传感器灵敏度为22.05 μA/mM/cm,线性检测范围为0.02~1.11 mM,最低检出限为2.7 μM,同时对干扰物质有良好的灵敏度、线性范围、检出限、选择性、重现性和长期稳定性,适合监测低血糖患者,防止血糖浓度过低造成心慌、昏迷等状况。Franco等开发了一种基于CuO的非酶便携式葡萄糖传感器,在纤维素布上印刷石墨烯浆料作为工作电极。此研究中,传感器在0.1~1 mM葡萄糖内具有良好的传感性能,灵敏度为(182.9±8.83%)μA/mM/cm。Xiao等开发了一种基于微流控芯片的可穿戴传感器,用于比色分析和汗液中葡萄糖的检测。该传感器的检测线性范围为0.1~0.5 mM,检出限为0.03 mM,可用来监测糖尿病患者,杜绝血糖浓度过高导致糖尿病酮症酸中毒、高血糖高渗综合征等病症。
2.3 用于监测生物分子的柔性汗液传感器
酪氨酸(Tyr)是与多种疾病相关的疾病标志物,如酪氨酸血症和神经性贪食症。Xu等展示了一种基于单宁酸银碳纳米管聚苯胺(TA-Ag-CNT-PANI)复合水凝胶的电化学传感器,用于检测pH值和Tyr。该可穿戴汗液传感器具有较高的灵敏度,较好的选择性、稳定性和重复性,且单宁酸螯合银纳米粒子(TA-AgNPs)和碳纳米管(CNTs)的存在显著提高了水凝胶的导电性和柔韧性,使复合水凝胶具有抗菌能力。
皮质醇由肾上腺合成,是一种应激激素,在能量代谢和电解质平衡等生理过程中发挥重要作用,影响记忆、睡眠和情绪等认知过程。因此皮质醇被认为是用于监测人类心理健康的生物标志物之一。Madhu等提出了一種基于纱线的电化学传感器平台。该传感器在1 fg/mL~1 μg/mL内呈良好的线性关系,循环伏安法和微分脉冲伏安法的检出限分别为0.45 fg/mL和0.098 fg/mL,灵敏度为2.12 μA/(g/mL),可用于皮质醇的快速检测。Sempionatto等制备了一种能够实时监测汗液中电解质和代谢产物的柔性免疫传感平台,将其集成在眼镜上,可用于高选择性及高灵敏度测定汗液中的皮质醇。传感器的检出限为0.3 fg/mL,检测范围为1 fg/mL~1 mg/mL。检测结果与市售化学发光免疫分析法基本一致,对皮质醇具有较高的灵敏度。该传感平台可作为汗液皮质醇的非侵入健康监测和临床诊断工具,适合对工作强度高、压力大的工作人群监测。
2.4 用于监测其他成分的柔性汗液传感器
酒精滥用对个人健康、交通安全和医疗保健都有有害影响。研究表明,汗液中的乙醇浓度与血液中乙醇浓度高度相关,从而可以通过监测汗液中乙醇浓度来判断血液中的酒精浓度。Kim等提出了一种用于酒精检测的可穿戴文身生物传感器系统。这种传感器使匹罗卡品药物通过经皮传递诱导汗液,并通过离子电泳和使用酒精氧化酶和普鲁士蓝电极换能器在产生的汗液中对乙醇进行安培检测。该方法在可穿戴的临时文身纸上使用丝网印刷技术制作所有电极,制备过程简单,成本低廉。
维生素在人体的正常新陈代谢中起着重要作用,是肌体维持正常功能所必需的物质和营养元素。维生素C可以预防和治疗血液系统疾病、恢复免疫系统、加速伤口愈合、皮肤管理,并增强身体的抗氧化能力。然而,大量摄入维生素C会导致肾脏疾病、血栓形成和结石。Sempoatto等提出了一种可穿戴的表皮生物传感器,用于无创追踪表皮汗液中维生素C的摄取浓度和动态趋势。酶促反应消耗的维生素C含量与抗坏血酸浓度成正比,服用维生素C片剂或饮用果汁后可监测氧化还原电流的变化,不受尿酸、乙酰氨基酚等汗液成分的干扰。结果证明,该传感器可用于评估膳食营养的跟踪,从而改善佩戴者的饮食行为,正确摄取营养。
咖啡因属于黄嘌呤生物碱,是一种相对安全的精神活性药物,广泛存在于咖啡、茶等产品中。由于咖啡因成瘾,它与生命和健康密切相关。Tai等开发了一种可穿戴式皮肤传感平台,用于无创、实时、连续的药物在线监测。研究表明,该传感器对咖啡因浓度的线性响应灵敏度为110 nA/μM,检测范围为0~40 μM,检出限为3×10 M,对尿素、葡萄糖、乳酸、抗坏血酸等干扰物质的响应小于9.2%。传感器捕捉咖啡因最高浓度的生理趋势的能力预计在30~120 min,构建的可穿戴汗液腕带成功实现了对汗液中甲基黄嘌呤类药物的连续监测。同时该平台的微分脉冲伏安法(DPV)检测技术还可以检测到其他类型的甲基黄嘌呤药物,为持续进行无创药物监测铺平了道路。
3 结 论
随着各种技术的发展,灵活的可穿戴传感器正在成为下一代智能可穿戴的工具,能够以智能、简便、实时的方式捕捉人体和周围环境的信息,从而被广泛应用于医疗、军事等领域。除了上述应用领域外,能与人体皮肤紧密贴合的可穿戴设备也在腕带、手环等领域迅速发展,然而,还存在一些问题。一是汗液的收集和利用。由于环境和生理差异,个体和身体部位的汗液含量存在差异。汗液的化学成分会因收集地点和提取方式的不同而有所不同,年龄和性别的差异也会影响汗液的成分。二是大多数情况下,传感器多采用聚合物薄膜作为基底,并使用贵金属作为导电电极,因此,透气性差、穿着舒适性差、价格高是这些传感器的主要缺点。三是除了佩戴汗液传感器的舒适性和汗液检测的灵敏度外,还需要考虑佩戴过程中人体运动和环境变化是否会影响检测性能和灵敏度。
针对以上问题,今后可以通过建立具有动态波动范围的标准化、个性化的汗液成分数据库,可为柔性传感器的进一步发展和应用奠定基础。开发天然且成本低的材料制备可穿戴纺织品汗液传感器已成为一种趋势,如纺织基底材料及纸基底材料,可以满足其佩戴的舒适性和透气性。随着研究人员对制备方法和实际应用的深入研究,柔性可穿戴传感器会更加具有广泛的应用前景,可穿戴设备有望在未来的日常健康和体育活动监测,以及疾病的预防、诊断、治疗和愈后等方面发挥重要作用。
参考文献:
[1]CHUNG M, SKINNER W H, ROBERT C, et al. Fabrication of a wearable flexible sweat pH sensor based on SERS-active Au/TPU electrospun nanofibers[J]. ACS Applied Materials & Interfaces, 2021, 13(43): 51504-51518.
[2]GHAFFARI R, YANG D S, KIM J, et al. State of sweat: Emerging wearable systems for real-time, noninvasive sweat sensing and analytics[J]. ACS Sensors, 2021, 6(8): 2787-2801.
[3]KIM J, CAMPBELL A S, AVILA B E F D, et al. Wearable biosensors for healthcare monitoring[J]. Nature Biotechnology, 2019, 37(4): 389-406.
[4]BAKER L B. Physiology of sweat gland function: The roles of sweating and sweat composition in human health[J]. Temperature, 2019, 6(3): 211-259.
[5]JIA J, XU C T, PAN S J, et al. Conductive thread-based textile sensor for continuous perspiration level monitoring[J]. Sensors, 2018, 18(11): 1-19.
[6]LUO D, SUN H B, LI Q Q, et al. Flexible sweat sensors: From films to textiles[J]. ACS Sensors, 2023, 8(2): 465-481.
[7]YIN J, LI J C, REDDY V S, et al. Flexible textile-based sweat sensors for wearable applications[J]. Biosensors, 2023, 13(1): 1-26.
[8]QIAO Y T, QIAO L J, CHEN Z M, et al. Wearable sensor for continuous sweat biomarker monitoring[J]. Chemosensors, 2022, 10(7): 1-53.
[9]YANG P F, WEI G F, LIU A, et al. A review of sampling, energy supply and intelligent monitoring for long-term sweat sensors[J]. Npj Flexible Electronics, 2022, 6(1): 1-13.
[10]TABASUM H, GILL N, MISHRA R, et al. Wearable microfluidic based e-skin sweat sensors[J]. RSC Advances, 2022, 12(14): 8691-8707.
[11]宋璟瑤, 黄蓉, 陈媛媛, 等. 基于导电材料的柔性汗液传感器的研究进展[J]. 分析化学, 2023, 51(5): 695-705.
SONG J Y, HUANG R, CHEN Y Y, et al. Research progress of flexible sweat sensors based on conductive materials[J]. Chinese Journal of Analytical Chemistry, 2023, 51(5): 695-705.
[12]唐丽琴, 李彦, 毛吉富, 等. 检测汗液用可穿戴电化学传感器的研究进展[J]. 纺织学报, 2023, 44(3): 221-230.
TANG L Q, LI Y, MAO J F, et al. Research progress in wearable electrochemical sensor for sweat detection[J]. Journal of Textile Research, 2023, 44(3): 221-230.
[13]MEI X C, YANG J, YU X G, et al. Wearable molecularly imprinted electrochemical sensor with integrated nanofiber-based microfluidic chip for in situ monitoring of cortisol in sweat[J]. Sensors and Actuators B: Chemical, 2023, 381: 133451.
[14]CHEN L J, CHEN F, LIU G, et al. Superhydrophobic functionalized TiCT MXene-based skin-attachable and wearable electrochemical pH sensor for real-time sweat detection[J]. Analytical Chemistry, 2022, 94(20): 7319-7328.
[15]CUI X Q, BAO Y, HAN T T, et al. A wearable electrochemical sensor based on β-CD functionalized graphene for pH and potassium ion analysis in sweat[J]. Talanta, 2022, 245: 123481.
[16]MAZZARA F, PATELLA B, D’AGOSTINO C, et al. PANI-based wearable electrochemical sensor for pH sweat monitoring[J]. Chemosensors, 2021, 9(7): 169.
[17]LIAO J J, ZHANG X Y, SUN Z H, et al. Laser-induced graphene-based wearable epidermal ion-selective sensors for noninvasive multiplexed sweat analysis[J]. Biosensors, 2022, 12(6): 1-11.
[18]BARBER R, CAMERON S, DEVINE A, et al. Laser induced graphene sensors for assessing pH: Application to wound management[J]. Electrochemistry Communications, 2021, 123: 106914.
[19]SUN H X, SONG S J, ZHAO G, et al. A flexible and wearable chemiresistive biosensor fabricated by laser inducing for real-time glucose analysis of sweat[J]. Advanced Materials Interfaces, 2023, 10(22): 2300281.
[20]ZHU Z D, SHI X Y, FENG Y T, et al. Lotus leaf mastoid inspired Ag micro/nanoarrays on PDMS film as flexible SERS sensor for in-situ analysis of pesticide residues on nonplanar surfaces[J]. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2023, 288: 122211.
[21]BAE C W, TOI P T, KIM B Y, et al. Fully stretchable capillary microfluidics-integrated nanoporous gold electrochemical sensor for wearable continuous glucose monitoring[J]. ACS Applied Materials & Interfaces, 2019, 11(16): 14567-14575.
[22]SHU Y, SHANG Z J, SU T, et al. A highly flexible Ni-Co MOF nanosheet coated Au/PDMS film based wearable electrochemical sensor for continuous human sweat glucose monitoring[J]. Analyst, 2022, 147(7): 1440-1448.
[23]OH S Y, HONG S Y, JEONG Y R, et al. Skin-attachable, stretchable electrochemical sweat sensor for glucose and pH detection[J]. ACS Applied Materials & Interfaces, 2018, 10(16): 13729-13740.
[24]WANG R, ZHAI Q F, AN T, et al. Stretchable gold fiber-based wearable textile electrochemical biosensor for lactate monitoring in sweat[J]. Talanta, 2021, 222: 121484.
[25]佘明華, 徐瑞东, 韦继超, 等. 纺织基柔性触觉传感器及可穿戴应用进展[J]. 丝绸, 2023, 60(3): 60-72.
SHE M H, XU R D, WEI J C, et al. Textile-based flexible tactile sensors and wearable applications[J]. Journal of Silk, 2023,60(3): 60-72.
[26]ZHAO Y M, ZHAI Q F, DONG D S, et al. Highly stretchable and strain-insensitive fiber-based wearable electrochemical biosensor to monitor glucose in the sweat[J]. Analytical Chemistry, 2019, 91(10): 6569-6576.
[27]ZHANG Y W, LIAO J J, LI Z H, et al. All fabric and flexible wearable sensors for simultaneous sweat metabolite detection and high-efficiency collection[J]. Talanta, 2023, 260: 124610.
[28]MUGO S M, LU W H, ROBERTSON S. A wearable, textile-based polyacrylate imprinted electrochemical sensor for cortisol detection in sweat[J]. Biosensors, 2022, 12(10): 1-13.
[29]SINGH A, SHARMA A, ARYA S. Human sweat-based wearable glucose sensor on cotton fabric for real-time monitoring[J].Journal of Analytical Science and Technology, 2022, 13(1): 1-13.
[30]MA H, LI J, ZHOU J, et al. Screen-printed carbon black/recycled Sericin@ Fabrics for wearable sensors to monitor sweat loss[J]. ACS Applied Materials & Interfaces, 2022, 14(9): 11813-11819.
[31]MO L, MA X D, FAN L F, et al. Weavable, large-scaled, rapid response, long-term stable electrochemical fabric sensor integrated into clothing for monitoring potassium ions in sweat[J]. Chemical Engineering Journal, 2023, 454: 140473.
[32]BAGHERI N, MAZZARACCHIO V, CINTI S, et al. Electroanalytical sensor based on gold-nanoparticle-decorated paper for sensitive detection of copper ions in sweat and serum[J]. Analytical Chemistry, 2021, 93(12): 5225-5233.
[33]LI T, LIANG B, YE Z C, et al. An integrated and conductive hydrogel-paper patch for simultaneous sensing of Chemical-Electrophysiological signals[J]. Biosensors and Bioelectronics, 2022, 198: 113855.
[34]PARRILLA M, VANHOOYDONCK A, WATTS R, et al. Wearable wristband-based electrochemical sensor for the detection of phenylalanine in biofluids[J]. Biosensors and Bioelectronics, 2022, 197: 113764.
[35]YANG M P, SUN N, LAI X C, et al. Paper-based sandwich-structured wearable sensor with sebum filtering for continuous detection of sweat pH[J]. ACS Sensors, 2023, 8(1): 176-186.
[36]Al-HARDAN N H, HAMID M A A, KENG L K, et al. Low-cost fabrication of a pH sensor based on writing directly over parchment-type paper with pencil[J]. Journal of Materials Science: Materials in Electronics, 2021, 32: 9431-9439.
[37]LI M, WANG L C, LIU R, et al. A highly integrated sensing paper for wearable electrochemical sweat analysis[J]. Biosensors and Bioelectronics, 2021, 174: 112828.
[38]YOUHANNA S, DEVUYST O. Editors’ digest-basic science a wearable sweat analyzer for continuous electrolyte monitoring[J]. Peritoneal Dialysis International Journal of the International Society for Peritoneal Dialysis, 2016, 36(5): 470.
[39]MO L, MA X D, FAN L F, et al. Weavable, large-scaled, rapid response, long-term stable electrochemical fabric sensor integrated into clothing for monitoring potassium ions in sweat[J]. Chemical Engineering Journal, 2023, 454: 140473.
[40]ZHANG J, ZHOU Q Q, CAO J D, et al. Flexible textile ion sensors based on reduced graphene oxide/fullerene and their potential applications of sweat characterization[J]. Cellulose, 2021, 28: 3123-3133.
[41]CURTO V F, COYLE S, BYRNE R, et al. Concept and development of an autonomous wearable micro-fluidic platform for real time pH sweat analysis[J]. Sensors and Actuators B: Chemical, 2012, 175(175): 263-270.
[42]HOU X S, ZHOU Y, LIU Y J, et al. Coaxial electrospun flexible PANI//PU fibers as highly sensitive pH wearable sensor[J]. Journal of Materials Science, 2020, 55: 16033-16047.
[43]HA J H, JEONG Y, AHN J, et al. A wearable colorimetric sweat pH sensor-based smart textile for health state diagnosis[J]. Materials Horizons, 2023(10): 4163-4171.
[44]SHITANDA I, MURAMATSU N, KIMURA R, et al. Wearable ion sensors for the detection of sweat ions fabricated by heat-transfer printing[J]. ACS Sensors, 2023, 8(7): 2889-2895.
[45]BARIYA M, NYEIN H Y Y, JAVEY A. Wearable sweat sensors[J]. Nature Electronics, 2018, 1(3): 160-171.
[46]GHOORCHIAN A, KAMALABADI M, MORADI M, et al. Wearable potentiometric sensor based on Na 0.44 MnO for non-invasive monitoring of sodium ions in sweat[J]. Analytical Chemistry, 2022, 94(4): 2263-2270.
[47]MAZZARACCHIO V, SERANI A, FIORE L, et al. All-solid state ion-selective carbon black-modified printed electrode for sodium detection in sweat[J]. Electrochimica Acta, 2021, 394: 139050.
[48]PIROVANO P, DORRIAN M, SHINDE A, et al. A wearable sensor for the detection of sodium and potassium in human sweat during exercise[J]. Talanta, 2020, 219: 121145.
[49]ALIZADEH A, BURNS A, LENIGK R, et al. A wearable patch for continuous monitoring of sweat electrolytes during exertion[J]. Lab on a Chip, 2018, 18(17): 2632-2641.
[50]PROMPHET N, RATTANAWALEEDIROJN P, SIRALERTMUKUL K, et al. Non-invasive textile based colorimetric sensor for the simultaneous detection of sweat pH and lactate[J]. Talanta, 2019, 192: 424-430.
[51]ONOR M, GUFONI S, LOMONACO T, et al. Potentiometric sensor for non invasive lactate determination in human sweat[J]. Analytica Chimica Acta, 2017, 989: 80-87.
[52]ZHANG Q W, JIANG D F, XU C S, et al. Wearable electrochemical biosensor based on molecularly imprinted Ag nanowires for noninvasive monitoring lactate in human sweat[J]. Sensors and Actuators B: Chemical, 2020, 320: 128325.
[53]WANG Y X, TSAO P K, RINAWATI M, et al. Designing ZIF-67 derived NiCo layered double hydroxides with 3D hierarchical structure for Enzyme-free electrochemical lactate monitoring in human sweat[J]. Chemical Engineering Journal, 2022, 427: 131687.
[54]XUAN X, YOON H S, PARK J Y. A wearable electrochemical glucose sensor based on simple and low-cost fabrication supported micro-patterned reduced graphene oxide nanocomposite electrode on flexible substrate[J]. Biosensors and Bioelectronics, 2018, 109: 75-82.
[55]王怡, 汪宇佳, 陳方春, 等. 蚕丝基葡萄糖传感器研究进展[J]. 丝绸, 2023, 60(3): 8-15.
WANG Y, WANG Y J, CHEN F C, et al. Research progress on silk-based glucose sensors[J]. Journal of Silk, 2023, 60(3): 8-15.
[56]ZHAI Q F, GONG S, WANG Y, et al. Enokitake mushroom-like standing gold nanowires toward wearable noninvasive bimodal glucose and strain sensing[J]. ACS Applied Materials & Interfaces, 2019, 11(10): 9724-9729.
[57]ZHAO Y M, ZHAI Q F, DONG D S, et al. Highly stretchable and strain-insensitive fiber-based wearable electrochemical biosensor to monitor glucose in the sweat[J]. Analytical Chemistry, 2019, 91(10): 6569-6576.
[58]OH S Y, HONG S Y, JEONG Y R, et al. Skin-attachable, stretchable electrochemical sweat sensor for glucose and pH detection[J]. ACS Applied Materials & Interfaces, 2018, 10(16): 13729-13740.
[59]WANG Y S, WANG X Q, LU W, et al. A thin film polyethylene terephthalate (PET) electrochemical sensor for detection of glucose in sweat[J]. Talanta, 2019, 198: 86-92.
[60]FRANCO F F, HOGG R A, MANJAKKAL L. CuO-Based electrochemical biosensor for non-invasive and portable glucose detection[J]. Biosensors, 2022, 12(3): 1-11.
[61]XIAO J Y, LIU Y, SU L, et al. Microfluidic chip-based wearable colorimetric sensor for simple and facile detection of sweat glucose[J]. Analytical Chemistry, 2019, 91(23): 14803-14807.
[62]XU Z Y, QIAO X J, TAO R Z, et al. A wearable sensor based on multifunctional conductive hydrogel for simultaneous accurate pH and tyrosine monitoring in sweat[J]. Biosensors and Bioelectronics, 2023, 234: 115360.
[63]KINNAMON D, GHANTA R, LIN K C, et al. Portable biosensor for monitoring cortisol in low-volume perspired human sweat[J]. Scientific Reports, 2017, 7(1): 13312.
[64]MADHU S, ANTHUUVAN A J, RAMASAMY S, et al. ZnO nanorod integrated flexible carbon fibers for sweat cortisol detection[J]. ACS Applied Electronic Materials, 2020, 2(2): 499-509.
[65]SEMPIONATTO J R, NAKAGAWA T, PAVINATTO A, et al. Eyeglasses based wireless electrolyte and metabolite sensor platform[J]. Lab on a Chip, 2017, 17(10): 1834-1842.
[66]KIM J, JEERAPAN I, IMANI S, et al. Noninvasive alcohol monitoring using a wearable tattoo-based iontophoretic-biosensing system[J]. ACS Sensors, 2016, 1(8): 1011-1019.
[67]HAUKE A, SIMMERS P, OJHA Y R, et al. Complete validation of a continuous and blood-correlated sweat biosensing device with integrated sweat stimulation[J]. Lab on a Chip, 2018, 18(24): 3750-3759.
[68]GRANGER M, ECK P. Dietary vitamin C in human health[J]. Advances in Food and Nutrition Research, 2018, 83: 281-310.
[69]SEMPIONATTO J R, KHORSHED A A, AHMED A, et al. Epidermal enzymatic biosensors for sweat vitamin C: Toward personalized nutrition[J]. ACS Sensors, 2020, 5(6): 1804-1813.
[70]MCLELLAN T M, CALDWELL J A, LIEBERMAN H R. A review of caffeine’s effects on cognitive, physical and occupational performance[J]. Neuroscience & Biobehavioral Reviews, 2016, 71: 294-312.
[71]TAI L C, GAO W, CHAO M H, et al. Methylxanthine drug monitoring with wearable sweat sensors[J]. Advanced Materials, 2018, 30(23): 1707442.
Research and application progress of flexible sweat sensors
YAN Han, LIU Liyan, LI Zhijie, LUO Dan, LIU Hao
(a.School of Textile Science and Engineering; b.Institute of Smart Wearable Electronic Textiles, Tiangong University, Tianjin 300387, China)
Abstract:Sweat is the liquid secreted by the sweat glands of the human body and is distributed in all parts of the body, while sweat contains a wealth of information about human health. In addition to water, sweat contains electrolytes, metabolites, heavy metals, hormones, proteins, etc. The levels of electrolytes and other components in sweat can change significantly depending on the physical condition and environmental conditions, so the assessment of human health status can be realized by monitoring specific components in sweat. Compared with other biological fluids, sweat is easy to be collected and shows unique advantages in the field of wearable sensors, especially in health tracking and monitoring during human movement. In recent years, the rapid development of flexible wearable sensors and electronic device technologies has greatly facilitated the research on wearable sweat sensors. Currently, portable devices have been developed to capture the energy in sweat and store it. As the research on flexible sweat sensors continues to deepen, corresponding progress has been made in the design of wearable flexible sweat sensors, which are expected to play a greater role in the fields of healthcare, human movement monitoring, and aerospace.
Flexible wearable electronic devices need to match the bending and stretching of human skin without affecting the wearer’s daily activities. Since most of the substrates of traditional wearable sensors are rigid and cannot meet the wearable use of people, the research of flexible substrate materials has become the focus of the field of flexible sensors at this stage. Starting from the types of substrate materials for flexible sweat sensors, this paper described in detail the substrate materials commonly used for sweat sensors in recent years and briefly outlined the applications of flexible sweat sensors in monitoring. Finally, it summarized the current limitations and prospects for future development.
Flexible wearable sensors are now becoming the next generation of smart wearable tools, capable of capturing information about the human body and its surroundings in an intelligent, easy and real-time manner. However, there are still some problems. Firstly, in terms of sweat collection and utilization, due to environmental and physiological differences, there are variations in sweat levels in individuals and body parts. The chemical composition of sweat can vary depending on where it is collected and how it is extracted. Age and gender differences also affect the composition of sweat. Secondly, in most cases, polymer films are used as substrates and precious metals as conductive electrodes for sensors; therefore, these sensors have such main drawbacks as poor breathability, wearing comfort and high price. Finally, in addition to the comfort of wearing the sweat sensor and the sensitivity of sweat detection, it is also necessary to consider whether human movement and environmental changes during the wearing process will affect the detection performance and sensitivity.
To address the above issues, a standardized and personalized sweat composition database with dynamic fluctuation range can be established in the future, which can lay the foundation for further development and application of flexible sensors. It has become a trend to develop natural and low-cost materials such as textile substrate materials and paper substrate materials for the preparation of wearable textile sweat sensors, which can satisfy the comfort and breathability of their wearing. With the researchers’ in-depth study of preparation methods and practical applications, flexible wearable sensors will be more widely used, and wearable devices are expected to play an important role in the future monitoring of daily health and physical activities, as well as in the prevention, diagnosis, treatment and healing of diseases.
Key words:sweat; sensor; flexible; smart wearable; health detection; application