Yoon Research Group
Miniaturized biochemical analysis system can be applied to autonomous instrument for environmental field measurement, automatic chemical analyzer and biomedical field such as blood analysis, micro dosing system, DNA analysis and etc. Our BioMEMS research includes study on bio-sensors, chemical-sensors, microfluidic devices and lab-on-chips.
A Flexible Fish-bone-shaped Neural Probe Strengthened by biodegradable Silk Coating for Enhanced BiocompatibilityChronic neural recording has long been challenged by the inevitable immune response that degrades the implanted electrode performance over time. This project presents a polyimide probe with a unique fish-bone geometry designed to minimize the tissue encapsulation near the electrode sites. By utilizing silk as a stiff and biodegradable coating, we can obtain the necessary strength for insertion of the flexible and miniaturized probe into the brain tissue.
Implantable neural probe capable of simultaneous optical stimulation of neurons and electrical recording of single unit neuronal potentialsRecently, optical stimulation has drawn much attention because genetically targeted neurons are selectively excited or inhibited by light at specific wavelengths. A photodefinable polymer (SU-8) has been patterned to form optical mixer and splitter waveguides. Single mode optical fibers have been coupled in grooves etched in the probe body. The distance between optical stimulation sites and electrical recording sites have been precisely controlled.
High-throughput PDT Screening ChipIn vitro efficacy assay is a routine prescreen step for anti cancer drug development including various showing up photosensitizers (drugs used in photodynamic therapy or PDT). As photodynamic therapy's action mechanism involves essential interactions among photosensitizer, oxygen and light, an in vitro test of photosensitizer requires controls of all three factors, and more detailed preclinical tests could provide better guidance for its potential optimum in-vivo protocols.
Single Cell Migration ChipCell migration is an essential process in angiogenesis, cancer metastasis, wound healing, inflammation and even embryogenesis. With this mechanism, cells can move into proper positions and enact appropriate functions in the body. There are a number of previous works reported to study cell migration in a microfluidic chip. Most works, however, have loaded and cultured thousands of cells in the same channel; thus, it is impossible to trace heterogeneous cell behaviors. In this work, we develop a high capture rate cell migration chip capable of tracing cell migration at a single-cell resolution readily after cell loading.
PDMS Hydrophobic Surfaces for High-throughput Cancer Spheroid CultureHydrophobic surfaces have become popular for anti-biofouling applications, but they can also be attractive platforms for non-adherent mammalian cell culture. Suspension growth of cancer cells allows for the identification and subsequent enrichment of cancer stem cells (CSCs) by confirming their ability to form spheres in suspension. We have achieved successful non-adherent spheroid culture of cancer cells on hydrophobic surfaces, formed in polydimethylsiloxane (PDMS), to be used in CSC enrichment and isolation. These surfaces have additionally been integrated within a single cell capture microfluidic device for high throughput performance.
Clonal culture and chemodrug assay of heterogeneous cells (pc3 prostate carcinoma cells) using microfluidic single cell array chips:A major obstacle in cancer research and treatment is that cancer cells often mutate or differentiate into multiple different cell types during experiments. Even testing a drug in a petridish culture might only give information that is averaged across multiple subtypes with very different resistance mechanisms. Recently it was reported that even PC3 human prostate carcinoma cells, a cell line, give rise to a mixture of three clonal phenotypes: holoclones, meroclones, and paraclones. We report a microfluidic array chip that can separate PC3 cancer cells into single cells in each microwell, grow them separately side by side into small uniform clonal colonies and test drugs on them. Using this chip we can detect how many subtypes of clones are present and to see if they respond differently to cancer drug treatments.
Microfluidic array chip for analysis of pairwise cell interaction by temporal stimulation of secreted factors using chamber isolation:Cellular processes like cancer metastasis and stem cell proliferation and differentiation are highly susceptible to cell-to-cell interaction. Cell-cell interaction analysis has been used to elucidate many cellular processes, but conventional methods are limited to averaged measurement of hundreds or even millions of cells, which is not always desirable and makes high-throughput testing problematic. To address this issue, we propose a new microfluidic device which can analyze pairwise cell interactions in isolated microchamber arrays, enabling hundreds of simultaneous tests and potential high-throughput screening of useful cell pairings. Soluble factors secreted by cells in each pair can quickly reach high physiological concentrations when trapped in a small chamber in proximity to each other, rather than being diluted in larger amounts of media as in conventional methods. Media exchange for cell viability is achieved by quick washes and media perfusion alternated with media isolation phases to expose cells to accumulated signals.
Microfluidic Array Chip for Single-Cell AssayThere has been growing interest in single-cell assays to understand single-cell behavior more accurately. To address this, different methods for single-cell assay using microfluidics have been developed by various research groups. Our research however developed the first microfluidic array platform which allows to both capture and isolate single-cells, and to monitor cell behavior in different environments.
Highly Efficient Single Cell Capturing Using Hydrodynamic Guiding StructuresA microfluidic chip array for high-throughput single cell assay with an efficient cell capture rate was presented. The single cell capture structure utilizes hydrodynamic resistance difference in flow paths and its feasibility was tested. More than 40% of all the injected microbeads were captured in the designated capture sites. The capture structure was expanded in an array of microwells formed at the intersection of rows and columns of orthogonal microchannels. By selectively operating integrated pneumatic valves, we successfully demonstrated cell seeding, reagents injection and cell isolation without cross-contamination.
Real-time label-free quantitative monitoring of biomolecules by floating-gate complementary metal-oxide semiconductor sensorWe report a label-free field-effect sensing array integrated with complementary metal-oxide semiconductor (CMOS) readout circuitry to detect the surface potential determined by the negative charge in DNA molecules. For real-time DNA quantification, we have demonstrated the measurements of DNA molecules without immobilizing them on the sensing surface which is composed of an array of floating-gate CMOS transistors. This nonimmobilizing technique allows the continuous monitoring of the amount of charged molecules by injecting DNA solutions sequentially. We have carried out the real-time quantitative measurement of 19 bp oligonucleotides and analyzed its sensitivity as a function of pH in buffer solutions.
Programmable Magnetic Cell Size SorterA programmable magnetic cell sorter to seperate different-sized cells was presented. The cell sorter consists of a series of seperating units, comprising ferromagnetic nickel lines and current-carrying gold lines. The magnetized nickel lines and the current of gold lines can generate local field and attract the cells coated with magnetic nanoparticles. By changing the current, we could control the local magnetic field, which enables the device to sort the target cell sizes selectively. We successfully demonstrated this scheme by sorting three different sizes (6, 10, and 15 .m in diameter) of magnetic beads under the different current of 21, 37, and 68mA/line to the gold lines in the fabricated microfluidic chip.
Active cell positioning using Dielectrophoresis (DEP)Many researches have been performed for the positioning and capturing of cells at single cell level in microfluidic systems for biological and biochemical analysis. However, in most of the previous works it was difficult to expand them into a 2-dimensional array because they only passively captured the cells and did not employ any accurate control of positioning/capturing cells one by one actively. In this work, we propose a new scheme for active positioning control of single cell using dielectrophoresis (DEP).
Antibody detection by using single bead-based assayQD-based detection has attracted research attention because of its numerous advantages such as high sensitivity, narrow emission bandwidth, long-term photostability and tunable multi-color imaging compared to conventional organic dyes. We propose a microbead-based assay for adaptive antibody detection by using a microfluidic chip designed to manipulate single microbead.
High throughput cell analysis and drug screeningThe need for high-throughput cell analysis/drug screening has been increased with the progress in biotechnology and combinatorial chemistry. In order to address the requirements of expensive equipments and long/tedious experimental works for highthroughput screening, a chip-based cell assay has been developed and reported in recent researches. However, in these previous devices it was relatively difficult to expand them into a two dimensional array with a large number of analysis sites. Also, the flow of cell suspension media or reagents should be maintained to be flowing into the captured cell in order to uphold the cells in each capturing site during the cell culturing and analysis. In this work, we propose a microfluidic chip with multiple micro-wells in two dimension arrays. The proposed chip provides a physical isolation in the captured cells using a PDMS membrane cover, so that a specific reagent can be introduced into each micro-well without continuously maintaining a cell suspension media flow.
Single-Cell analysis chipCells are usually influenced by a mixture of hormones, ions, and neurotransmitters released from neighboring cells. Dynamic monitoring of a single cell is important for individual cell analysis without the influence of neighboring cells in independently controlled environments. In our research, we have developed a microfluidic chip in which a single-cell is autonomously captured in a cell-positioning site by a pre-defined fluid stream and a specific liquid flow including drugs or reagents can be consecutively supplied to each single-cell through a flow injection channel.
A Disposable DNA sample preparation microfluidic chipThe Nucleic Acid (NA) probe assays typically include PCR to amplify the number of copies of DNA to a detectable level. The PCR technique requires a relatively pure DNA sample in aqueous solution, free of inhibitors during the PCR process. Therefore, the extraction and purification of nucleic acids from biological samples are the critical steps that should be carefully handled in the NA assays. In this work we have proposed a new microfluidic chip to address this sample preparation process for NA probe assays.