Seung-Hei Cho - Academia.edu (original) (raw)

Papers by Seung-Hei Cho

Analyte-detecting sensors have been developed in many fields. Chemical sensors, and especially bi... more Analyte-detecting sensors have been developed in many fields. Chemical sensors, and especially biomedical sensors, deserve special attention because they can simplify time-consuming, costly and site-limited medical procedures. Sensor efficiency depends on its analyte sensing material, signal transducing device and data processing system. The biggest barrier to devise biomedical sensors is the development of analyte sensing material with a high selectivity for target molecules. The motivation of this research was to develop biomolecule-sensitive polymers that can be used in biomedical sensors. Thus, this thesis covers all stages of chemical sensor development, from developing target analyte sensitive materials to merging the developed materials with a signal transducing system. First, the potential application of a zwitterionic glucose-responsive hydrogel as a body implantable continuous glucose monitoring system was examined. After using thermodynamics to confirm the glucose sensing mechanism, synthesis of the hydrogels was optimized and analyzed using statistical methods (design of experiments (DOE)). Thermodynamics study showed that mixing contribution was an important factor to glucose selectivity as well as elastic contribution. By the DOE study, we confirmed that sensitivity of the hydrogels was determined by the molar ratio of cationic and anionic functional groups, and response time depended on the amount of cross-linker. A hydrogel degradation study was also performed to determine the effect of gamma ray sterilization and neutron irradiations on the hydrogel cross-linking network for biomedical applications. Results showed that gamma ray affected cross-linking networks of UV cured hydrogels. However, the neutron irradiation effect was not considerable. In addition, ferromagnetic particles-embedded, zwitterionic glucose-responsive hydrogels were developed to enable the response processing by a magnetoresistive transducer. The hydrogel with horizontally aligned ferromagnetic particles showed good sensitivity in the physiological glucose range (~10 mM). Moreover, response time was reduced by almost seven-fold with twice thicker samples (800 um) than samples (400 um) with a pressure sensor measurement. A second project optimized the synthesis of a glutathione (GSH)-sensitive polymer. The selectivity of the polymer for GSH was improved by synthesizing a GSHimprinted polymer and adopting a cobalt ion-mediated chelating binding structure as analyte binding sites.

Probe with hairpin and template sections for biochip testing

Smart Hydrogels Designed for use in Microfabricated Sensor Arrays

MRS Proceedings, 2013

ABSTRACTHydrogels are considered smart materials because they respond to environmental stimuli. S... more ABSTRACTHydrogels are considered smart materials because they respond to environmental stimuli. Sensors that monitor the body’s pH levels would be helpful for doctors to determine the severity of a patient’s condition, especially if they exhibit signs of shock. The motivation of this project is to create a biomedical device that can be worn sublingually or implanted into the body to help doctors with diagnosing a patient’s condition. The magnitude of the swelling/deswelling behavior can be measured by placing a sample of the hydrogel in a piezoresistive sensor. The degree of swelling/deswelling is directly proportional to the change in pH of the aqueous solution it is placed in. In this study, a variety of compositions of pH responsive hydrogels were designed and tested to determine the response time and magnitude for use in both macro and micro sensor arrays. This pressure sensor has been designed for use with thinner gels than have been used in the past. The results for swelling t...

Effect of temperature changes on the performance of ionic strength biosensors based on hydrogels and pressure sensors

Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference, 2011

Stimuli responsive hydrogels show a strong ability to change in volume with changes in selected e... more Stimuli responsive hydrogels show a strong ability to change in volume with changes in selected environmental properties. This tendency of these hydrogels to change in volume is captured as pressure-change in confined cavities of pressure sensors. An array of pressure sensors on a single chip may carry hydrogels sensitive to multiple, selected metabolic markers and continuously monitor multiple vital parameters simultaneously. Currently, such sensors are capable of continuously monitoring pH, ionic strength, glucose levels and temperature in the sensor environment. In this paper, we report the effect of temperature changes on the performance of ionic strength sensor. A formulation of hydrogel that renders it sensitive to changes in ionic strength was UV polymerized in situ in piezoresistive pressure sensors with different membrane sizes. The sensor sensitivity, response time and stability are investigated as a function of temperature in vitro. The effect of temperature on these sens...

Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference, 2010

In this paper, we present preliminary results showing the response of glucose-sensitive hydrogels... more In this paper, we present preliminary results showing the response of glucose-sensitive hydrogels, confined in micro-pressure sensors, to the changes in environmental glucose concentration. The glucose concentrations were incrementally varied between 20 and 0mM in 0.15M PBS solution at 7.4 pH and bovine serum at 7.4 pH at room temperature and response of the sensor was recorded. The micro sensors demonstrate a response time of 10 minutes in both PBS and serum. Tissue response after 55 days of subcutaneous implantation of a EtO sterilized sensor in mice is presented. The preliminary analysis of the surrounding tissue shows inflammation which is believed not to interfere with the sensor performance.

Sensors and Actuators B: Chemical, 2011

Because the boronic acid moiety reversibly binds to sugar molecules and has low cytotoxicity, bor... more Because the boronic acid moiety reversibly binds to sugar molecules and has low cytotoxicity, boronic acid-containing hydrogels are being used in a variety of implantable glucose sensors under development, including sensors based on optical, fluorescence, and swelling pressure measurements. However, some method of glucose selectivity enhancement is often necessary, because isolated boronic acid molecules have a binding constant with glucose that is some forty times smaller than their binding constant with fructose, the second most abundant sugar in the human body. In many cases, glucose selectivity enhancement is obtained by incorporating pendant tertiary amines into the hydrogel network, thereby giving rise to a hydrogel that is zwitterionic at physiological pH. However, the mechanism by which incorporation of tertiary amines confers selectivity enhancement is poorly understood. In order to clarify this mechanism, we use the osmotic deswelling technique to compare the thermodynamic interactions of glucose and fructose with a zwitterionic smart hydrogel containing boronic acid moieties. We also investigate the change in the structure of the hydrogel that occurs when it binds to glucose or to fructose using the technique of small angle neutron scattering.

Effects of gamma rays and neutron irradiation on the glucose response of boronic acid-containing “smart” hydrogels

Polymer Degradation and Stability, 2014

ABSTRACT If a biomaterial is to be implanted in the body, it must be subjected to a sterilization... more ABSTRACT If a biomaterial is to be implanted in the body, it must be subjected to a sterilization procedure which often involves gamma irradiation. We report results for the effects of γ-irradiation on the glucose response of a hydrogel with glucose-binding boronic acid moieties. This ‘smart” hydrogel is of a type suitable for use in non-enzymatic glucose sensors. In addition, the effect of neutron irradiation on the glucose response of these hydrogels is also of interest, because the hydrogels could be used with minor modification to deliver boron to tumors during boron neutron capture therapy (BNCT). We show that the glucose response of the smart hydrogels is unaffected by exposure to neutrons in the dose range typical for BNCT. The effect of gamma rays on the glucose response depends on the method used to cure the smart hydrogel. If the hydrogel is cured with a thermal free-radical-initiator, then the hydrogel can be sterilized by gamma irradiation with no adverse effects upon the glucose response. However, if the hydrogel is cured with a UV-initiated free radical initiator, then the glucose response decreases in magnitude with increase in the gamma radiation dose.

Macromolecular Research, 2007

To achieve targeted drug delivery for chemotherapy, a ligand-mediated nanoparticulate drug carrie... more To achieve targeted drug delivery for chemotherapy, a ligand-mediated nanoparticulate drug carrier was designed, which could identify a specific receptor on the surfaces of tumor cells. Biodegradable poly(ethylene oxide)/poly(ε-caprolactone) (PEG/PCL) amphiphilic block copolymers coupled to biotin ligands were synthesized with a variety of PEG/PCL compositions. Block copolymeric nanoparticles harboring the anticancer drug paclitaxel were prepared via micelle formation in aqueous solution. The size of the biotin-conjugated PEG/PCL nanoparticles was determined by light scattering measurements to be 88-118 nm, depending on the molecular weight of the block copolymer, and remained less than 120 nm even after paclitaxel loading. From an in vitro release study, biotin-conjugated PEG/PCL nanoparticles containing paclitaxel evidenced sustained release profiles of the drug with no initial burst effect. The biotin-conjugated PEG/PCL block copolymer itself evidenced no significant adverse effects on cell viability at 0.005-1.0 μg/mL of nanoparticle suspension regardless of cell type (normal human fibroblasts and HeLa cells). However, biotin-conjugated PEG/PCL harboring paclitaxel evidenced a much higher cytotoxicity for cancer cells than was observed in the PEG/PCL nanoparticles without the biotin group. These results showed that the biotinconjugated nanoparticles could improve the selective delivery of paclitaxel into cancer cells via interactions with overexpressed biotin receptors on the surfaces of cancer cells.

Smart Hydrogel-Based Biochemical Microsensor Array for Medical Diagnostics

Wearable/Wireless Body Sensor Networks for Healthcare Applications, 2012

With the rapid development of micro systems technology and microelectronics, smart implantable wi... more With the rapid development of micro systems technology and microelectronics, smart implantable wireless electronic systems are emerging for the continuous surveillance of relevant parameters in the body and even for closed-loop systems with a sensor feed-back to drug release systems. With respect to diabetes management, there is a critical societal need for a fully integrated sensor array that can be used to continuously measure a patient’s blood glucose concentration, pH, pCO2 and colloid oncotic pressure twenty four hours a day on a long-term basis. In this work, thin films of metabolite-specific or “smart” hydrogels were combined with microfabricated piezoresistive pressure transducers to obtain “chemomechanical sensors” that can serve as selective and versatile wireless biomedical sensors and sensor arrays for a continuous monitoring of several metabolites. Sensor response time and accuracy with which sensors can track gradual changes in glucose, pH, CO2 and ionic strength, resp...

Reliable continuous sensors are salient to achieving advanced Process Analytical Technologies in ... more Reliable continuous sensors are salient to achieving advanced Process Analytical Technologies in the bioproduction industry. Sensors provide information on key parameters in a bioreactor such as physical variables (temperature, pressure, speed of stirrer), chemical variables (pH, pO2, pCO2, nutrients, metabolites), and biological variables (biomass, cell metabolism).1-2 Simultaneously, chemometric analysis using multivariate data analysis, bioprocess modeling, and design of experiments (DOE) have become important in developing advanced biosensors because of the need to clean the complex raw data from biosensors to provide repeatable, robust, and reliable information.3-4 In this work, the first step of the chemometric analysis process, DOE was performed with a prototype biosensor developed to simultaneously monitor glucose, lactate, pH, and osmolarity to understand the accuracy and selectivity of this sensor. Sets of experiments for the DOE were designed with 4 factors (glucose, lact...

Journal of Applied Polymer Science, 2014

A stimuli-responsive hydrogel that contains the anionic monomer 3-acrylamidophenylboronic acid an... more A stimuli-responsive hydrogel that contains the anionic monomer 3-acrylamidophenylboronic acid and the cationic monomer N-[3-(dimethylamino)propyl]acrylamide binds with cis-diol groups of glucose molecules selectively and reversibly. Even though such hydrogels have good selectivity for glucose, there are still remaining thresholds that should be overcome to enhance the sensitivity (swelling pressure response magnitude) and to reduce the response time (inverse of 1st order rate constant). In this study, the sensitivity and response time of zwitterionic glucose sensitive hydrogels (GSHs) were studied with three factor DOE analysis. The DOE results show that the molar ratio of 3-acrylamidophenylboronic acid/N-[3-(dimethylamino)propyl]acrylamide and the wt % of monomer in the pregel solution are the most important factors for enhancing the hydrogel sensitivity. In addition, fast response times can best be achieved by decreasing the molar ratio of cross-linker. The results of this study will be useful as guidelines for the optimal synthesis of glucose sensitive hydrogels.

Implantable Biosensor Arrays Based On Smart Hydrogels And Piezoresistive Sensors For Continuous Metabolic Monitoring

Procedia Engineering, 2011

In this paper, we present the results of continuous monitoring metabolic sensor arrays capable of... more In this paper, we present the results of continuous monitoring metabolic sensor arrays capable of monitoring changes in glucose, ionic strength and pH in the surrounding analyte continuously. Piezoresistive pressure sensors containing KOH etched cavities and pressure sensing membranes with and without perforations were fabricated in different sizes (1.5×1.5 mm 2 , 1.25×1.25 mm 2 , 1×1 mm 2 and 0.5×0.5 mm 2) to account for the sensitivities of the different types of hydrogels that were investigated. Figure 1 shows the schematic and the image of the sensors. Stimuli responsive hydrogels were used as the sensing elements to detect glucose and ionic strength in phosphate buffered saline at pH 7.4 and at room temperature. Response times of ~10 and ~6 minutes during swelling cycle and ~5 and ~4 minutes for the shrinking cycle were measured for glucose and ionic strength responsive hydrogels respectively.

Method and Apparatus for Mixing Fluids