Tiangco Cristina, Andar Abhay, Quarterman Juliana, Ge Xudong, Sevilla Fortunato, Rao Govind, Stinchcomb Audra, Bunge Annette, Tolosa Leah
Center for Advanced Sensor Technologycsm, University of Maryland Baltimore County, 1000 Hilltop Circle, Baltimore, MD, 21250, USA.
The Graduate School, University of Santo Tomas, España Boulevard, 1015, Manila, Philippines.
Anal Bioanal Chem. 2017 May;409(13):3475-3482. doi: 10.1007/s00216-017-0289-7. Epub 2017 Mar 10.
Current glucose monitoring techniques for neonates rely heavily on blood glucose monitors which require intermittent blood collection through skin-penetrating pricks on the heel or fingers. This procedure is painful and often not clinically conducive, which presents a need for a noninvasive method for monitoring glucose in neonates. Our motivation for this study was to develop an in vitro method for measuring passive diffusion of glucose in premature neonatal skin using a porcine skin model. Such a model will allow us to initially test new devices for noninvasive glucose monitoring without having to do in vivo testing of newborns. The in vitro model is demonstrated by comparing uncompromised and tape-stripped skin in an in-line flow-through diffusion apparatus with glucose concentrations that mimic the hypo-, normo-, and hyper-glycemic conditions in the neonate (2.0, 5.0, and 20 mM, respectively). Transepidermal water loss (TEWL) of the tape-stripped skin was approximately 20 g m h, which closely mimics TEWL for neonatal skin at about 190 days post-conceptional age. The tape-stripped skin showed a >15-fold increase in glucose diffusion compared to the uncompromised skin. The very small concentrations of collected glucose were measured with a highly selective and highly sensitive fluorescent glucose biosensor based on the glucose binding protein (GBP). The demonstrated method of glucose determination is noninvasive and painless, which makes it especially desirable for glucose testing in neonates and children. This study is an important step towards an in vitro model for noninvasive real-time glucose monitoring that may be easily transferred to the clinic for glucose monitoring in neonates. Graphical Abstract Glucose diffusion through model skin was measured using an in-line flow-through diffusion apparatus with glucose solutions mimicking hypo-, normo- and hyperglycemia in the neonate. Phosphate buffered saline was added to the top chamber and the glucose that diffused through the model skin into the buffer was measured using a fluorescent glucose binding protein biosensor.
目前用于新生儿的血糖监测技术严重依赖血糖仪，而血糖仪需要通过足跟或手指的皮肤穿刺进行间歇性采血。该操作很痛苦，而且在临床上往往并不适宜，因此需要一种无创的新生儿血糖监测方法。我们开展这项研究的目的是利用猪皮模型开发一种体外方法，用于测量葡萄糖在早产新生儿皮肤中的被动扩散。这样的模型将使我们能够初步测试用于无创血糖监测的新设备，而无需对新生儿进行体内测试。通过在在线流通扩散装置中比较完整皮肤和胶带剥离皮肤，使用模拟新生儿低血糖、正常血糖和高血糖状况（分别为2.0、5.0和20 mM）的葡萄糖浓度，展示了该体外模型。胶带剥离皮肤的经表皮水分流失（TEWL）约为20 g m h，这与孕龄约190天的新生儿皮肤的TEWL非常相似。与完整皮肤相比，胶带剥离皮肤的葡萄糖扩散增加了15倍以上。使用基于葡萄糖结合蛋白（GBP）的高选择性和高灵敏度荧光葡萄糖生物传感器测量收集到的极少量葡萄糖。所展示的葡萄糖测定方法是无创且无痛的，这使其特别适用于新生儿和儿童的血糖检测。这项研究是朝着建立用于无创实时血糖监测的体外模型迈出的重要一步，该模型可能很容易转移到临床用于新生儿血糖监测。图形摘要 使用在线流通扩散装置，用模拟新生儿低血糖、正常血糖和高血糖的葡萄糖溶液测量葡萄糖通过模型皮肤的扩散。将磷酸盐缓冲盐水加入上腔室，使用荧光葡萄糖结合蛋白生物传感器测量通过模型皮肤扩散到缓冲液中的葡萄糖。
