Paper-based Microfluidic Device for Bisphenol A Based Chemical Reaction and Image Analysis

박형근,김자영,여민경 한국바이오칩학회 2016 BioChip Journal Vol.10 No.1

Bisphenol A (BPA) is a representative xenoestrogenic endocrine disruptor that is widely used in consumer products and remains in wastewater. A simple detection tool is urgently needed that can be used with the naked eye for environmental monitoring in situ. Therefore we studied modification methods of phenol and ferric reagents on a paper-based microfluidic device. The reaction between BPA and ferric reagent mixtures was examined using two types of ferric reagent mixtures (ferric chloride/ferricyanide and ferric nitrate/ferricyanide) at various ferric reagent mixture ratios (1 : 9, 3 : 7, 5 : 5, 7 : 3 and 9 : 1) and concentrations (BPA 100, 300, 500 and 1000 μg/mL and 1-5% ferric reagent mixtures). Verification of this paper- based microfluidic device was analyzed with a UV spectrophotometer. In addition, the changing color of the BPA reaction was demonstrated using histograms of the image statistics including the hue, saturation and value (HSV) analysis. Of the total BPA reactions, the optimal condition was identified as 1% ferric reagent mixture (5 : 5 ratio) and 5 μL of BPA loaded onto the paper-based microfluidic device. Moreover, the BPA detection abilities of ferric chloride/ferricyanide and ferric nitrate/ ferricyanide were similar to the changing images on the paper-based microfluidic device. The BPA paperbased microfluidic device is expected to be applied in situ and in factories as a low-cost, portable, simple and rapid detection system. Bisphenol A (BPA) is a representative xenoestrogenic endocrine disruptor that is widely used in consumer products and remains in wastewater. A simple detection tool is urgently needed that can be used with the naked eye for environmental monitoring in situ. Therefore we studied modification methods of phenol and ferric reagents on a paper-based microfluidic device. The reaction between BPA and ferric reagent mixtures was examined using two types of ferric reagent mixtures (ferric chloride/ferricyanide and ferric nitrate/ferricyanide) at various ferric reagent mixture ratios (1 : 9, 3 : 7, 5 : 5, 7 : 3 and 9 : 1) and concentrations (BPA 100, 300, 500 and 1000 μg/mL and 1-5% ferric reagent mixtures). Verification of this paper-based microfluidic device was analyzed with a UV spectrophotometer. In addition, the changing color of the BPA reaction was demonstrated using histograms of the image statistics including the hue, saturation and value (HSV) analysis. Of the total BPA reactions, the optimal condition was identified as 1% ferric reagent mixture (5 :5 ratio) and 5 μL of BPA loaded onto the paper-based microfluidic device. Moreover, the BPA detection abilities of ferric chloride/ferricyanide and ferric nitrate/ ferricyanide were similar to the changing images on the paper-based microfluidic device. The BPA paperbased microfluidic device is expected to be applied in situ and in factories as a low-cost, portable, simple and rapid detection system.

Paper-based Cell Culture Microfluidic System

Fang Fang Tao,Xia Xiao,Kin Fong Lei,I-Chi Lee 한국바이오칩학회 2015 BioChip Journal Vol.9 No.2

In the past decades, glass/PDMS-basedmicrofluidic systems have been rapidly developed to provide homogenous and stable microenvironment for culturing cells. Although these excellent demonstrations involve much simplified operations than traditional cell culture protocol, but they are still not readily accessible to untrained personnel and not appropriate to operate in conventional biological laboratories. In this work, cellulose filter papers were used for the substrates of the cell culture microfluidic system, which provides a convenient tool for cell-based assay. A paper was patterned with culture areas and channels by wax printing technique. Medium or tested substance can be passively perfused to the culture areas. Analyses of cyto-compatibility, cell proliferation, cell morphology, and cell chemosensitivity were performed to confirm the possibility of the paper-based system. Theculture system could provide a platform for a wide range of cell-based assays with applications in drug screening and quantitative cell biology. This work demonstrated a paper-based cell culture microfluidic system and the system is inexpensive, disposable, and compatible to the existing culture facility. In the past decades, glass/PDMS-based microfluidic systems have been rapidly developed to provide homogenous and stable microenvironment for culturing cells. Although these excellent demonstrations involve much simplified operations than traditional cell culture protocol, but they are still not readily accessible to untrained personnel and not appropriate to operate in conventional biological laboratories. In this work, cellulose filter papers were used for the substrates of the cell culture microfluidic system, which provides a convenient tool for cell-based assay. A paper was patterned with culture areas and channels by wax printing technique. Medium or tested substance can be passively perfused to the culture areas. Analyses of cyto-compatibility, cell proliferation, cell morphology,and cell chemosensitivity were performed to confirm the possibility of the paper-based system. The culture system could provide a platform for a wide range of cell-based assays with applications in drug screening and quantitative cell biology. This work demonstrateda paper-based cell culture microfluidic system and the system is inexpensive, disposable, and compatible to the existing culture facility.

Double-sided electrohydrodynamic jet printing of two-dimensional electrode array in paper-based digital microfluidics

Jafry, Ali Turab,Lee, Hyungdong,Tenggara, Ayodya Pradhipta,Lim, Hosub,Moon, Youngkwang,Kim, Seung-Hyun,Lee, Yongwoo,Kim, Sung-Min,Park, Sungsu,Byun, Doyoung,Lee, Jinkee Elsevier 2019 Sensors and actuators. B Chemical Vol.282 No.-

<P><B>Abstract</B></P> <P>Double-sided electrohydrodynamic jet printing of circuitry using silver nanowires (AgNWs) and dispensing of high viscosity silver nanoparticles (AgNPs) is demonstrated for the first time in the fabrication of a two-dimensional array of electrodes (3D circuitry) on a single sheet of paper. The penetration of AgNW ink through the paper’s thickness by capillary imbibition allows for multilayer electrical access to connect the individual electrodes. This makes it an automated and efficient choice as the functional area of the device is conserved and the surface of the paper is preserved. This allows for two-dimensional droplet manipulation on a paper-based digital microfluidics (PBDMF) platform. Compared to printed circuit board technology, paper-based electronics offer a range of desirable properties: they are light weight, portable, economical, flexible, biodegradable, and the materials are abundantly available. The fabricated PBDMF chip is demonstrated to be a low-cost, fully reconfigurable, and disposable point-of-care diagnostic platform for the environmental sensing of pesticide using organophosphorus hydrolase enzyme through colorimetric detection via smartphone.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Silver nanowires penetrated through paper’s thickness for making 3D interconnects. </LI> <LI> High viscosity silver nanoparticles dispensed on paper reveal no penetration. </LI> <LI> 3D circuitry in single sheet of paper printed using double-sided EHD jet printing. </LI> <LI> Two-dimensional droplet actuation achieved on a paper-based digital microfluidics. </LI> <LI> Cellphone-based colorimetric detection of methyl paraoxon from 10 to 100 μM concentration. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Pressed region integrated 3D paper-based microfluidic device that enables vertical flow multistep assays for the detection of C-reactive protein based on programmed reagent loading

Park, Juhwan,Park, Je-Kyun Elsevier 2017 Sensors and actuators. B Chemical Vol.246 No.-

<P><B>Abstract</B></P> <P>Although vertical flow assays (VFAs) have a number of advantages compared to lateral flow assays (LFAs) such as a short analysis time, no line interference, and no Hook effect, VFAs are not preferred as LFAs because of their complicated operation principle. In this study, we demonstrated VFAs with multistep reactions for the detection of C-reactive protein (CRP) based on the programmed reagent loading in a pressed region integrated 3D paper-based microfluidic device. The flow order of all reagents in a 3D paper-based microfluidic device was programmed based on the delayed flow caused by the pressed region as well as the geometry modification of the paper channel. After simultaneous loading of all the reagents required for assays, they are sequentially loaded into the analysis region with a programmed sequence. As a proof of concept, a high-sensitivity CRP (hs-CRP) detection with signal amplification was performed to predict the riskiness of cardiovascular disease within 15min. The detection limit was improved from 0.01 to 0.005μg/mL via a maximum 3.47-fold signal amplification. Additionally, the upper limit of hs-CRP detection increased to 5μg/mL without Hook effect. Finally, we successfully detected hs-CRP in a clinically relevant range (0.005–5μg/mL), while LFAs cannot cover due to the Hook effect.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Vertical flow assays (VFAs) with multistep reactions were performed in a 3D paper-based microfluidic device. </LI> <LI> Programmed loading of all reagents into the analysis region was achieved by utilizing a delayed flow in a pressed paper. </LI> <LI> Upper limit and sensitivity of the assays were increased without Hook effect compared to lateral flow assays (LFAs). </LI> <LI> C-Reactive protein was detected for the prediction of cardiovascular disease in a clinical range (0.005–5μg/mL). </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

A comparative study of paper-based microfluidic devices with respect to channel geometry

Jafry, A.T.,Lim, H.,Kang, S.I.,Suk, J.W.,Lee, J. Elsevier 2016 Colloids and surfaces. A, Physicochemical and engi Vol.492 No.-

<P>Since 2007, the world of microfluidics saw an emergence of a new era of low cost, simple, quick fabrication, abundantly available, and environmentally friendly microfluidic paper-based analytical devices (PADs) capable of clinical diagnostics, food quality control as well as environmental monitoring. Although many fabrication techniques have evolved as a result of its broad application spectrum and ease of use, the technology has still barely scratched the surface of its potential in terms of its underlying fundamental principle, i.e., fluid flow analysis. In this study, we report the comparison of flow profile attained by using two of the most promising techniques of photolithography and wax printing from a hydrodynamic point of view. A modified protocol for synthesizing an epoxy based negative photoresist (SU-8) channel and wax-based channel was created by optimizing a few process parameters of our equipment. Water and oil (oleic acid) are selected as the hydrophilic and hydrophobic fluids, respectively, and their flow was analyzed in straight channels using a paper device. A new approach to vary the flow velocity is described in detail involving cylindrical dots as the resistance inside the paper channel. Observing the length-time curve for the two fluids, it becomes evident that both follow the Lucas-Washburn equation if the width of the channel is large enough. Various configurations of dots indicate that different longitudinal flow velocity implying its application in simultaneous addition of chemicals without the need to change the channel width or length. (C) 2016 Elsevier B.V. All rights reserved.</P>

Flow control in paper-based microfluidic device for automatic multistep assays: A focused minireview

정성근,김종민,진시형,Ki-Su Park,이창수 한국화학공학회 2016 Korean Journal of Chemical Engineering Vol.33 No.10

Although lateral flow tests (LFTs) are easy-to-use diagnostics, they have fundamental limitations for sequential multistep assay that can be reduced to a single chemical reaction step. Paper-based microfluidic devices have attracted considerable attention for use in automatic multi-step assays because paper can be an excellent platform to control sequential fluid flow without external equipment. This review focuses on recent developments on how to control flow rate in paper-based microfluidic devices for automating sequential multi-step assays. The aim of this review is to discuss the limitations of LFTs and potential paper-based microfluidic devices for automated sequential multi-step assays in developing countries; and the existing fluidic control technologies for sequential multi-step assays. In addition, we present future challenges for commercialization of paper-based microfluidic devices to perform automatic multi-step assays.

하이드로젤에 의해 구동되는 종이 미세 유체 장치 용 펌프

서재덕(Jaedeok Seo),김원정(Wonjung Kim) 대한기계학회 2017 대한기계학회 춘추학술대회 Vol.2017 No.11

As paper-based microfluidic devices become diverse and used for detailed diagnostics, developers are making efforts to increase and control the flow in paper. The flow in the paper is the capillary flow described by the Washburn’s equation. The flow is determined by the size of pore and the properties of the working fluid. In order to generate a flowrate over this capillary flow, a high pressure is required to overcome the viscous resistance produced by the small size paper pore. We have used hydrogel as an energy source to create this high pressure. Hydrogels have the ability to absorb more than 100 times their volume of water and are already being applied in a variety of industrial and environmental applications. We have succeeded in producing a large negative pressure by creating a structure that maximizes the ability of the hydrogel to absorb water. We have developed a non-powered pump that can be used in paper-based devices using hydrogels. The pump can generate more than 20 times higher flowrate than the capillary flow in paper channel for more than 4 hours.

Paper-based microfluidic device fabrication using stamp method

최진솔,정헌호 한국공업화학회 2021 한국공업화학회 연구논문 초록집 Vol.2021 No.0

Paper-based microfluidic device for metal ion detection using stamp method

최진솔,정헌호 한국공업화학회 2022 한국공업화학회 연구논문 초록집 Vol.2022 No.-

An animal cell culture monitoring system using a smartphone-mountable paper-based analytical device

Im, S.H.,Kim, K.R.,Park, Y.M.,Yoon, J.H.,Hong, J.W.,Yoon, H.C. Elsevier Sequoia 2016 Sensors and actuators. B Chemical Vol.229 No.-

We developed a simple and low-cost cell culture monitoring system utilizing a paper-based analytical device (PAD) and a smartphone. The PAD simultaneously analyses glucose and lactate concentrations in the cell culture medium. Focusing on the fact that animal cells consume glucose and produce lactate under anaerobic conditions, oxidase- and horseradish peroxidase (HRP) enzyme-mediated colorimetric assays were integrated into the PAD. The PAD was designed to have three laminated layers. By using a double-sided adhesive tape as the middle layer and wax coating, a bifurcated fluidic channel was prepared to manipulate sample flow. At the inlet and the outlets of the channel, a sample drop zone and two detection zones for glucose and lactate, respectively, were positioned. When sample solution is loaded onto the drop zone, it flows to the detection zone through the hydrophilic fluidic channel via capillary force. Upon reaching the detection zone, the sample reacts with glucose and lactate oxidases (GOx and LOx) and HRP, immobilized on the detection zone along with colorless chromophores. By the Trinder's reaction, the colorless chromophore is converted to a blue-colored product, generating concentration-dependent signal. With a gadget designed to aid the image acquisition, the PAD was positioned to the smartphone-embedded camera. Images of the detection zones were acquired using a mobile application and the color intensities were quantified as sensor signals. For the glucose assay using GOx/HRP format, we obtained the limit of detection (LOD ~0.3mM) and the limit of quantification (LOQ ~0.9mM) values in the dynamic detection range from 0.3 to 8.0mM of glucose. For lactate assay using LOx/HRP, the LOD (0.02mM) and the LOQ (0.06mM) values were registered in the dynamic detection range from 0.02 to 0.50mM of lactate. With the device, simultaneous analyses of glucose and lactate in cell culture media were conducted, exhibiting highly accurate and reproducible results. Based on the results, we propose that the optical sensing system developed is feasible for practical monitoring of animal cell culture.