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Design, Fabrication, and Theoretical Investigation of a Cost-Effective Laser Printing Based Colorimetric Paper Sensor for Non-Invasive Glucose and Ketone Detection
bioRxiv - Biophysics Pub Date : 2021-09-24 , DOI: 10.1101/2021.09.23.461386
Manikuntala Mukhopadhyay , Sri Ganesh Subramanian , K. Vijaya Durga , Debashish Sarkar , Sunando DasGupta

Diabetes, a chronic condition, is one of the prevalent afflictions of the 21st century, and if left unchecked, this ailment could lead to severe life-threatening complications. A widely accepted methodology for monitoring diabetes is the estimation of the glucose and ketone contents in the body-fluids, viz. blood, urine, etc. Additionally, certain conditions such as starvation, and following a protein rich diet (e.g., keto-diet) could also lead to significant changes in the ketone content, thereby resulting in false-positive diagnosis. Hence, a precise, portable, and on-demand procedure for the rapid and combined estimation of glucose and ketone in the bodily-fluids is of utmost importance. To that end, paper-based analytical devices (μPADs) are promising tools, owing to their multitudinous advantages, and compatibility with biofluids. Although, numerous researchers have contributed substantially in the fundamental investigation, design, and fabrication of μPADs for various applications, a combined platform capable of rapid, accurate and on-demand glucose and ketone detection, that is easy to fabricate, is still relatively unexplored. Moreover, the flow dynamics of an analyte, in combination with enzyme-catalysed (for glucose) and uncatalyzed reactions (for ketone), within a porous paper matrix is also vaguely understood. Herein, we present a facile laser-printing based fabrication of colorimetric sensors on a filter paper, for rapid, and non-invasive estimation of glucose and ketone contents in urine. The urine sample, upon being deposited in a particular expanse, is wicked through the paper matrix, and reacts with specific reagents in the designated zone(s), giving rise to a final color, concomitant with the glucose or ketone content in the sample. The device design enables the liquid to be wicked into the porous matrix in a way that would concentrate the colored product in a dedicated detection zone, thereby augmenting the feasibility for accurate colorimetric detection. Furthermore, we present for the first time, a detailed dynamic model of the flow-field in a variable cross-section paper device using the Richards’ equation, while also considering the species transport and reaction kinetics within the porous media. The results of the numerical simulation agree well with those observed experimentally, thereby validating the present model. Finally, we also developed a web and desktop-based application that would enable the user to upload the images of the colored zones to provide an accurate estimate of the glucose and ketone content in the sample. We believe that our model, in combination with the proposed fabrication methodology, and the in-house developed app., would enable rapid and reliable fabrication of μPADs for various fundamental investigations, and applications pertaining to affordable health-care monitoring.

中文翻译:

一种用于非侵入式葡萄糖和酮检测的基于成本效益的激光打印比色纸传感器的设计、制造和理论研究

糖尿病是一种慢性病,是 21世纪普遍存在的疾病之一。世纪,如果不加以控制,这种疾病可能会导致严重的危及生命的并发症。一种广泛接受的糖尿病监测方法是估计体液中的葡萄糖和酮含量,即。血液、尿液等。此外,某些情况,如饥饿和富含蛋白质的饮食(例如,酮饮食)也可能导致酮含量的显着变化,从而导致假阳性诊断。因此,一种用于体液中葡萄糖和酮的快速组合估计的精确、便携和按需程序至关重要。为此,纸基分析设备 (μPAD) 由于其众多优势和与生物流体的兼容性而成为很有前途的工具。虽然,许多研究人员在用于各种应用的 μPAD 的基础研究、设计和制造方面做出了重大贡献,但一个能够快速、准确和按需检测葡萄糖和酮的组合平台,易于制造,但仍相对未开发。此外,分析物的流动动力学,结合酶催化(对于葡萄糖)和未催化反应(对于酮),在多孔纸基质内的流动动力学也模糊不清。在这里,我们提出了一种基于激光打印的在滤纸上的比色传感器的简单制造,用于快速、非侵入性地估计尿液中的葡萄糖和酮含量。尿样在沉积在特定区域后,通过纸基质进行芯吸,并与指定区域中的特定试剂发生反应,产生最终颜色,伴随样品中的葡萄糖或酮含量。该装置设计使液体能够以一种将有色产品集中在专用检测区的方式吸入多孔基质,从而增加了准确比色检测的可行性。此外,我们首次提出了使用理查兹方程的可变截面纸装置中流场的详细动力学模型,同时还考虑了多孔介质内的物质传输和反应动力学。数值模拟的结果与实验观察到的结果非常吻合,从而验证了本模型。最后,我们还开发了一个基于 Web 和桌面的应用程序,使用户能够上传彩色区域的图像,以准确估计样品中的葡萄糖和酮含量。我们相信,我们的模型结合所提出的制造方法和内部开发的应用程序,将能够快速可靠地制造 μPAD,用于各种基础研究以及与负担得起的医疗保健监测相关的应用。
更新日期:2021-09-27
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