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CURRENT RESEARCH PROJECTS OF THE NOH GROUP
• Cell Biology on a Chip
	» Human Liver on a Chip: Engineering Liver Sinusoid Functional Unit » Microfabricated Platforms for 3D Epithelial Culture: Matrigel Micropatterns for 3D Morphogenesis and Cancer Cell Migration/Invasion Studies
• AC/DC Electrokinetics
	» Manipulation of Micro-, Nano-, and Bioparticles Using AC Electrokinetics » Enhancing Binding Kinetics Using AC Electroosmotic Mixing » Microchip Capillary Electrophoresis for Single Cell Proteomics
• Microfluidic Devices for Medical Applications
	» Implantable Microdevice for the Treatment of Hydrocephalus » Disposable Micropump for Insulin Delivery » Disposable Microchip for RBC Deformability Measurement
• Other Projects
	» Micro-Fludics Lab (MFL) Modules and Kit for Undergraduate Education » A Novel Nanochannel Construction Technique and Nanoscale Fluid Flows
“If we knew what it was we were doing, it would not be called research, would it”? -Albert Einstein
PROJECT ABSTRACTS
Cell Biology on a Chip
Human Liver on a Chip: Engineering Liver Sinusoid Functional Unit (Sponsored by NSF and State of Pennsylvania) Fundamental liver biology studies predominantly rely on cell culture models. While much progress has been made during the past two decades in prolonging hepatocyte viability and maintaining liver functions in vitro, there are still no authentic liver models that accurately represent the architecture and functions of human liver tissue, thereby limiting advances in liver biology studies and drug development. A new approach to generate an authentic human liver model is proposed in this project. The liver lobule is composed of operational units termed the liver sinusoid, where most of the liver activities take place. The goal of this research is to generate an innovative human liver model (bioreactor) that closely mimics the liver sinusoid functional unit. Microfabrication and microfluidics technologies are combined with cell culture technology to create such an authentic human liver model. (Collaborator: Prof. Michael Bouchard of Biochemistry and Microbiology department)
Microfabricated Platform for 3-D Epithelial Culture: Matrigel Micropatterns for 3D Morphogenesis and Cancer Cell Migration/Invasion Studies Most human cancers arise from epithelial cells and tissues. In order to understand the mechanisms of tumor initiation and progression, it is crucial to investigate how the genotypic and molecular abnormalities associated with epithelial cancers actually derive the phenotypic changes that are observed in tumors in vivo. Three dimensional (3D) epithelial culture systems, which allow epithelial cells to recapitulate several aspects of glandular epithelial architecture in vivo, may serve as optimal in vitro model for biochemical and cell biological studies involving tumor initiation, progression, and metastasis. In this project we develop microfabricated/microfluidic platforms for 3D epithelial culture that will allow a wide range of applications for high throughput cell-based screening of chemicals, and gene targeting assays. The platform has an array of 3D micropatterns of Matrigel^TM (most widely used extracellular matrix for 3D epithelial culture) on a substrate and single mammary epithelial cells are cultured in the patterned Matrigel to form 3D normal acini (polarized, growth-arrested, hollow acini-like sphere) with continuous perfusion of media. (Collaborator: Prof. Mauricio Reginato of Biochemistry and Microbiology department).
AC/DC Electrokinetics
Manipulation of Micro-, Nano-, and Bioparticles Using AC Electrokinetics There is a growing need for a technique to manipulate micro-, nano-, and bioparticles in microfluidic environments as lab-on-a-chip research advances. Among currently available techniques, AC electrokinetic techniques that include dielectrophoresis (DEP), AC electroosmosis (AC-EO), and electrothermal effect (ETE) are best suited for the microfluidic applications because the techniques require microelectrodes that can be readily integrated within microchannels and because diverse manipulation of fluids and suspended particles can be achieved simply by changing the frequency of the applied voltage. The goal of this research to achieve a comprehensive understanding and accurate prediction of particle motion in a non-uniform AC field which is at present unavailable, and to develop a combination of DEP, AC-EO, and ETE into a versatile and convenient particle-manipulation technique for micro-, nano-, and biotechnology applications.
Enhancing Binding Kinetics Using AC Electroosmotic Mixing A chief characteristic for all biosensors is detection time. Regardless of other capabilities, (sensitivity, dynamic range, specificity, etc.) poor detection time can dramatically limit the usefulness of any biosensor. In general, the rate-limiting process is the transport of analyte to the transducer surface. In order to enhance the binding kinetics of biosensors electrohydrodynamic (EHD) effects may be utilized to create convective mixing near the surface of the sensor. This mixing will ensure that fresh reagent is continuously delivered to the sensor surface. The EHD mixing device is simple, contains no moving parts, uses very little space and should not affect the sensing capabilities of the transducer. Such an improvement to the detection time can be realized for a wide variety of sensor types (acoustic, optical, thermal…) and can have a great impact on the fields of diagnostics, bio-warfare agent detection and environmental and food monitoring among others. In this project, a thickness shear mode (TSM) sensor and ELISA assay are used as test cases. (Collaborator: Prof. Ryszard Lec of Biomedical Engineering)
Microchip Capillary Electrophoresis for Single Cell Analysis Seemingly identical cells are often quite heterogeneous in their chemical composition and biological activity and in the responses to drugs or external stimuli. Conventional biochemical assays that sample thousands of cells ignore the intracellular heterogeneity and thus fail to provide the rich information available when single cells are studied. Accurate analysis of the identity and quantity of proteins within individual cells would unveil numerous molecular pathways involved in metabolic processes and disease progression leading to development of new drugs, and would also enable the detection and identification of rare, abnormal cells in large populations of cells, potentially providing early diagnosis of diseases. Microchip capillary electrophoresis (μCE) is a powerful analytical technique that can provide an accurate molecular analysis of single cells. However, the adoption of μCE in single cell analysis has been hampered by the absence of automated, high-throughput system. The low throughput is mainly due to time-consuming cell handling and processing steps currently followed. The objective of this project is to develop an integrated μCE system for high-throughput, sequential proteomic analysis (> 100 cells/min) of single cells. The proposed integrated system consists of sequential cell delivery, continuous cell lysis, preconcentration of proteins, and effective electrophoretic separation. (Collaborators: Prof. Bahktier Farouk of Mechanical Engineering and Prof. Vanlila Swami of Pathology and Laboratory Medicine Department)
Microfluidic Devices for Medical Applications
Implantable Microdevice for the Treatment of Hydrocephalus (Sponsored by NIH and State of Pennsylvania) Cerebrospinal fluid (CSF) is a water-like fluid produced in the brain that circulates around and protects the brain and spinal cord. It is believed that CSF is absorbed into the superior sagittal sinus through biologic one-way valves called arachnoid villi, which are located in dura mater. Hydrocephalus is an abnormal accumulation of CSF within the subarachnoid space of the brain due to impaired CSF absorption. Hydrocephalus is one of the most frequently encountered problems in Neurosurgery. Currently, hydrocephalus is treated by a surgical procedure, performed by a neurosurgeon, in which a tube called a shunt is placed into the patient's body. The shunt systems for diverting CSF from the intracranial compartment was developed in 1960’s and has remained essentially unchanged for the last 40 years. In this project we attempt to replace the deficient arachnoid villi (AV) that produce the pathologic condition of communicating hydrocephalus with a micro-fabricated device to restore the normal absorptive function. The microfabricated arachnoid villi (MAV) will be implanted against the dura mater. (Collaborator: Dr. Francis Kralick of Neurosurgery @ Hanehmann Hospital)
Disposable Micropump for Lab on a Chip and Drug Delivery: Magnetically-actuated PDMS Micropump Fluid control is an essential part in lab-on-a-chip systems. Accurate fluid dispensing is also important in drug delivery systems such as insulin pump. The goal of this project is to develop versatile, low-cost (disposable) micropumps for drug delivery and lab-on-a-chip applications. PDMS-based magnetic micropumps are currently under development. The device consists of a magnetic membrane actuator, an electromagnet, and two passive valves. Pumps are designed to have self-priming capability and the flow rate ranges 1-100 ul/min.
Disposable Microchip for Red Blood Cell Deformability Measurement Erythrocytes (red blood cells) are characteristically very deformable and have many elastic properties to allow them to squeeze through the small capillaries at such extremities without sacrificing their shape and, consequently, their function. With the progression of a disease such as diabetes, the erythrocytes begin to lose their plasticity and become more rigid as the patient’s condition worsens. This accounts for the loss of blood flow to such extremities where the capillary diameter is small enough to prevent passage of rigid cells, thus preventing oxygen delivery, which results in tissue necrosis. Currently there is no way to instantaneously measure the plasticity of erythrocytes through simple techniques that can be employed at minimal cost and effort within a doctor’s clinic. Also, there is no current method for measuring the progression of diseases such as diabetes within the clinic by use of simple means that can produce results within minutes. The goal of this project is to invent a novel approach to measuring the deformability of erythrocytes so that the method can be employed by doctors in their clinics at reasonable costs and operation expenses. (Collaborators: Prof. Young Cho of Mechanical Engineering and Prof. Vanlila Swami of Pathology and Laboratory Medicine Department)
Other Projects
Development of Microfluidics Laboratory Modules and Kits (Sponsored by NSF) Microfluidics technology is rapidly spreading and is widely becoming adapted to many areas of industry and research. In spite of the rapidly growing need for both microfluidics technology and a trained workforce, the current undergraduate curricula of most engineering schools are not well prepared to meet the need. Most engineering programs do not offer microfluidics education in their curricula. This is mainly due to (1) lack of faculty expertise, (2) lack of necessary facilities, (3) the very tight curriculum occupied by traditional engineering subjects, and (4) lack of commercially available and affordable educational materials for training and experimentation. The main objective of this project is to develop and test a set of laboratory modules and kits that will allow engineering and science undergraduate students to explore microscale fluid behaviors and microfluidic devices. (Collaborators: Prof. David Wootton of Cooper Union, Prof. Fredricka Reisman of College of Education)
A Novel Nanochannel Construction Technique and Nanoscale Fluid Flows Nanoscale fluidic systems may offer unprecedented tools for molecular level sensing and analysis. Challenges in nanofluidics include difficulty of integrating nanochannel with micro-/macroworld and of introducing fluid into the tiny channels. A novel fabrication technique that effectively integrates nanochannel(s) with microfluidic components is developed. Carbon nanotubes are aligned on microelectrodes using dielectrophoresis followed by photo- and soft lithography to add microfluidic connection to the nanochannel. Different flow actuation mechanisms such as pressure-driven flow, capillary effect, and electrokinetically driven flows are studied using the nanofluidic devices.