Kim Semin, Kim Geehong, Ji Yong Woo, Moon Chae-Eun, Jung Yuna, Lee Hyung Keun, Lee JaeJong, Koh Won-Gun
Department of Chemical and Biomolecular Engineering, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-749, Republic of Korea.
Korea Institute of Machinery & Materials, Nano-Convergence Mechanical Systems Research Division, 156 Gajeongbuk-ro, Yuseong-gu, Daejeon, 34103, Republic of Korea.
Bioact Mater. 2022 Nov 29;23:383-393. doi: 10.1016/j.bioactmat.2022.11.010. eCollection 2023 May.
Bioresponsive hydrogels are smart materials that respond to various external stimuli and exhibit great potential as biosensors owing to their capability of real-time and label-free detection. Here, we propose a sensing platform based on bioresponsive hydrogels, employing the concept of moiré patterns. Two sets of line patterns with different pitch sizes are prepared; a hydrogel grating whose pitch size changes according to external stimuli and a reference grating with constant pitch size. The volume changes of the hydrogel caused by external stimuli changes the pitch size of the hydrogel grating, and subsequently, the pitch sizes of the moiré patterns (moiré signal), whose values can be obtained in a real-time and label-free manner through customized moiré microscopy and signal processing. After confirming that the pH-induced swelling of hydrogel could be monitored using moiré patterns, we performed moiré pattern-based detection of specific proteins using protein-responsive hydrogel that underwent shrinking via interaction with target proteins. Brain-derived neurotrophic factor and platelet-derived growth factor were selected as the model proteins, and our proposed system successfully detected both proteins at nanomolar levels. In both cases, the pitch size change of hydrogel grating was monitored much more sensitively using moiré patterns than through direct measurements. The changes in the moiré signals caused by target proteins were detected in environments using a custom-made intraocular lens incorporating the hydrogel grating, demonstrating the capability of the proposed system to detect various markers in intraocular aqueous humor, when implanted in the eye.
生物响应性水凝胶是一种智能材料，能够对各种外部刺激做出反应，由于其具有实时和无标记检测的能力，作为生物传感器具有巨大潜力。在此，我们基于生物响应性水凝胶提出了一种传感平台，采用了莫尔条纹的概念。制备了两组具有不同间距尺寸的线图案；一种间距尺寸根据外部刺激而变化的水凝胶光栅和一种间距尺寸恒定的参考光栅。外部刺激引起的水凝胶体积变化改变了水凝胶光栅的间距尺寸，随后，莫尔条纹的间距尺寸（莫尔信号）发生变化，其值可通过定制的莫尔显微镜和信号处理以实时和无标记的方式获得。在确认使用莫尔条纹可以监测水凝胶的pH诱导肿胀后，我们使用与靶蛋白相互作用而收缩的蛋白质响应性水凝胶对特定蛋白质进行了基于莫尔条纹的检测。选择脑源性神经营养因子和血小板源性生长因子作为模型蛋白，我们提出的系统成功地在纳摩尔水平检测到了这两种蛋白。在这两种情况下，使用莫尔条纹监测水凝胶光栅的间距尺寸变化比直接测量更为灵敏。在含有水凝胶光栅的定制人工晶状体的环境中检测到了靶蛋白引起的莫尔信号变化，这表明当植入眼中时，所提出的系统能够检测眼内房水中的各种标志物。
