Sensor design on inexpensive substrates for biochemical applications

This research project focuses on exploring new sensor design methods on inexpensive substrates for various biomedical and chemical applications, in order to improve the health and life quality of people living in less-industrialized countries and remote regions. People living in these areas are more susceptible to diseases due to shortage of funds, medical facilities, medical knowledge and professional staff. This project has noticed that for most existing point-of-care diagnostics designed for developing areas, although are affordable, sensitive, specific and rapid (“ASSR”), cannot be practically utilized in these areas, for they are not easily operated by non-professional and untrained personnel. In particular, a desirable user-oriented device is required to be user-friendly, equipment-free and delivered to end-users (“UED”), and achieving these demands, therefore, is the aim of this project. This thesis includes two parts, presenting two original sensor design concepts respectively. One is the “sample-only” method, which only requires the user to introduce the sample to the sensor with no extra effort during the assay; the other one is the “text-reporting” method, which can report the assay result directly with unambiguous text messages to the user. Both of the two concepts effectively address the “UED” problems in existing devices. The sensors developed by the new design concepts were conducted through fabrication on inexpensive substrates, which are cellulose paper and plastic (or glass) slides throughout this research. The patterning of these substrates is processed through traditional industrialized surface treatment, paper-sizing and printing techniques, making the devices affordable and easily-obtained. The feasibility of these two concepts is then demonstrated through applying them to practical applications. The first application is blood typing. The “sample-only” method allows the user to get clear blood typing results by only introducing one blood drop during the assay. The “text-reporting” method designs the first paper-based blood typing device that reports a patient’s blood type in written text, which enables non-professional users to determine the blood types immediately. Furthermore, the “text-reporting” method also presents its desirable features in another application: environmental monitoring. With the help of text-based information, even untrained users can quickly and simply obtain the testing result of contaminates in water at home, in the field, in emergency and many other areas where laboratories are not readily available. None of these applications requires supporting equipment and personnel for assay analysis and result interpretation. The applications performed by the new sensor design methods in this project bring the test immediately and conveniently to the patients or end-users, and effectively reduce the high-dependency of testing on hospitals or central laboratories. The sensor design concepts explored in this project establish the “ASSURED” platform which is highly practical for use by non-professional users in developing countries. These methods also hold enormous potential for integration with future work, which would strongly drive the development of products for point-of-care, telemedicine and on-site environmental sensing

Sensor design on inexpensive substrates for biochemical applications

This research project focuses on exploring new sensor design methods on inexpensive substrates for various biomedical and chemical applications, in order to improve the health and life quality of people living in less-industrialized countries and remote regions. People living in these areas are more susceptible to diseases due to shortage of funds, medical facilities, medical knowledge and professional staff. This project has noticed that for most existing point-of-care diagnostics designed for developing areas, although are affordable, sensitive, specific and rapid (“ASSR”), cannot be practically utilized in these areas, for they are not easily operated by non-professional and untrained personnel. In particular, a desirable user-oriented device is required to be user-friendly, equipment-free and delivered to end-users (“UED”), and achieving these demands, therefore, is the aim of this project. This thesis includes two parts, presenting two original sensor design concepts respectively. One is the “sample-only” method, which only requires the user to introduce the sample to the sensor with no extra effort during the assay; the other one is the “text-reporting” method, which can report the assay result directly with unambiguous text messages to the user. Both of the two concepts effectively address the “UED” problems in existing devices. The sensors developed by the new design concepts were conducted through fabrication on inexpensive substrates, which are cellulose paper and plastic (or glass) slides throughout this research. The patterning of these substrates is processed through traditional industrialized surface treatment, paper-sizing and printing techniques, making the devices affordable and easily-obtained. The feasibility of these two concepts is then demonstrated through applying them to practical applications. The first application is blood typing. The “sample-only” method allows the user to get clear blood typing results by only introducing one blood drop during the assay. The “text-reporting” method designs the first paper-based blood typing device that reports a patient’s blood type in written text, which enables non-professional users to determine the blood types immediately. Furthermore, the “text-reporting” method also presents its desirable features in another application: environmental monitoring. With the help of text-based information, even untrained users can quickly and simply obtain the testing result of contaminates in water at home, in the field, in emergency and many other areas where laboratories are not readily available. None of these applications requires supporting equipment and personnel for assay analysis and result interpretation. The applications performed by the new sensor design methods in this project bring the test immediately and conveniently to the patients or end-users, and effectively reduce the high-dependency of testing on hospitals or central laboratories. The sensor design concepts explored in this project establish the “ASSURED” platform which is highly practical for use by non-professional users in developing countries. These methods also hold enormous potential for integration with future work, which would strongly drive the development of products for point-of-care, telemedicine and on-site environmental sensing

Sequential droplet reactions for surface-bound gold nanocrater array

Femtoliter droplet array exhibit unique stability in contact with a flow. This work demonstrates that reactive femtoliter droplets enables sequential chemical reactions that may be leveraged to simplify the process for producing surface-bound materials. Gold nanocraters (GNCs) are formed on a planar substrate from biphasic reactions between water-insoluble thiol droplets and two aqueous solutions in sequence. The detailed process is that gold precursor solution was injected into a flow chamber hosting a substrate with thiol droplet array in a chamber, followed by injection of a reductant solution. The thiol droplets absorb and weakly bond with gold ions in a precursor solution. Subsequent exposure to a reductant solution accelerates the formation of gold clusters in droplets. The final nanoparticles form GNCs over a large surface area, due to fast formation around the droplet rim. The shape of an individual domain was controlled by the duration of ion absorption in the first step of the sequential reaction. Reacting droplets were followed in time by total internal reflection microscope to understand the reaction process. Morphology and composition of GNCs were characterized by atomic force microscope, SEM, microspectrophotometer, and X-Ray photoelectron spectrometer. We demonstrate that the as-prepared GNCs exhibits stable catalytic activity in degradation of azo dyes for multiple cycles. Compared to many current approaches for producing surface-bound nanomaterials, our approach is based on sequential droplet reactions in a flow-in process. This approach offers unique flexibility in varying independently the reactant concentration and reaction time of each step in the sequential reaction. The synthesized surface-bound catalytic nanomaterials may be applied in water treatment, optical display or fluorescence imaging

A zero-step functionalization on paper-based biosensing platform for covalent biomolecule immobilization

As a potential platform for point-of-care clinical analyses and environment monitoring, paper biosensors have received considerable attention. In many cases, the conjugation of biomolecules onto paper surface is crucial for increasing the functionalities of paper-based bioanalytical devices. Until now, it is sometimes argued as in the literature that finding a surface chemistry for biomolecule covalent grafting to paper still remains a challenge. Here the study shows that at least to a certain extent some aspects of the argument involved is questionable, by demonstrating that paper without any modification could be utilized for the covalent conjugation of enzymes and serves as a tool for bioanalysis. Moreover, the detailed analysis of biomolecule immobilization strategies on paper through polysaccharide-coating chemistry has been offered as a contrast. We believe that the proposed method could provide a valuable perspective for paper-based biosensors. Keywords: Biomolecule immobilization, Paper-based biosensors, Polysaccharide coating, Unmodified pape

Formation of Multicomponent Surface Nanodroplets by Solvent Exchange

Multicomponent surface droplets that consist of more than one compound are of great interest for fundamental studies of microwetting, evaporation, and dissolution behaviors, as well as for practical applications in high-throughput screening, microcompartmentalized chemical reactions, and microanalytics. In this work, we study the formation of multicomponent surface nanodroplets from heterogeneous nucleation and growth induced by the process of solvent exchange. In our experiments, as a solution of two oils in their good solvent was displaced by a poor solvent of the oils in the standard solvent exchange, binary droplets of oils were produced on an immersed substrate. The concentration of one oil was constant in the initial solution, whereas the other oil was increased gradually. We characterized the ratio of the two oils inside individual binary droplets by an infrared microspectrometer. Our results show that the ratio of two oils within binary nanodroplets could be varied from 0 to 100% by tuning the composition of the initial solution. However, the ratio of the two oils in the droplets did not simply correspond to that in the solution. Rather, we were able to correlate the ratio of the oils in the droplet to the oversaturation level of each oil based on the ternary phase diagram. We further demonstrate that the principle of the oversaturation level also governs the components in ternary nanodroplets formed by solvent exchange. The quantitative understanding in this work is valuable for the formation of multicomponent surface nanodroplets, which may be applied in nanoextraction, microcompartmentalized reactions, and surface functionalization

Strategy To Enhance the Wettability of Bioacive Paper-Based Sensors

This paper reports a potential method that can restore the wettability of bioactive paper-based sensors while maintaining their bioactivity. This study is driven by the need to increase the wettability of the antibody-loaded blood typing paper devices in order to increase the blood typing assaying speed using such paper devices. Plasma treatment is used to improve the wettability of bioactive paper; the protective effect of bovine serum albumin (BSA) to biomolecules against plasma deactivation is investigated. In the first stage, horseradish peroxidase (HRP) was used as a model biomolecule, because of the convenience of its quantifiable colorimetric reaction with a substrate. By using this protection approach, the inactivation of biomolecules on paper during the plasma treatment is significantly slowed down. This approach enables plasma treatment to be used for fabricating paper-based bioactive sensors to achieve strong wettability for rapid penetration of liquid samples or reagents. Finally, we demonstrate the use of plasma treatment to increase the wettability of antibody treated blood typing paper. After the treatment, the blood typing paper becomes highly wettable; it allows much faster penetration of blood samples into the plasma treated testing paper. Antibodies on the paper are still sufficiently active for blood typing and can report patients’ blood type accurately

Understanding Thread Properties for Red Blood Cell Antigen Assays: Weak ABO Blood Typing

“Thread-based microfluidics” research has so far focused on utilizing and manipulating the wicking properties of threads to form controllable microfluidic channels. In this study we aim to understand the separation properties of threads, which are important to their microfluidic detection applications for blood analysis. Confocal microscopy was utilized to investigate the effect of the microscale surface morphologies of fibers on the thread’s separation efficiency of red blood cells. We demonstrated the remarkably different separation properties of threads made using silk and cotton fibers. Thread separation properties dominate the clarity of blood typing assays of the ABO groups and some of their weak subgroups (A_<i>x</i> and A₃). The microfluidic thread-based analytical devices (μTADs) designed in this work were used to accurately type different blood samples, including 89 normal ABO and 6 weak A subgroups. By selecting thread with the right surface morphology, we were able to build μTADs capable of providing rapid and accurate typing of the weak blood groups with high clarity