Unyoung Kim

Multitarget magnetic activated cell sorter

Magnetic selection allows high-throughput sorting of target cells based on surface markers, and it is extensively used in biotechnology for a wide range of applications from in vitro diagnostics to cell-based therapies. However, existing methods can only perform separation based on a single parameter (i.e., the presence or absence of magnetization), and therefore, the simultaneous sorting of multiple targets at high levels of purity, recovery, and throughput remains a challenge. In this work, we present an alternative system, the multitarget magnetic activated cell sorter (MT-MACS), which makes use of microfluidics technology to achieve simultaneous spatially-addressable sorting of multiple target cell types in a continuous-flow manner. We used the MT-MACS device to purify 2 types of target cells, which had been labeled via target-specific affinity reagents with 2 different magnetic tags with distinct saturation magnetization and size. The device was engineered so that the combined effects of the hydrodynamic force produced from the laminar flow and the magnetophoretic force produced from patterned ferromagnetic structures within the microchannel result in the selective purification of the differentially labeled target cells into multiple independent outlets. We demonstrate here the capability to simultaneously sort multiple magnetic tags with >90% purity and >5,000-fold enrichment and multiple bacterial cell types with >90% purity and >500-fold enrichment at a throughput of 109 cells per hour.

Selection of mammalian cells based on their cell-cycle phase using dielectrophoresis

An effective, noninvasive means of selecting cells based on their phase within the cell cycle is an important capability for biological research. Current methods of producing synchronous cell populations, however, tend to disrupt the natural physiology of the cell or suffer from low synchronization yields. In this work, we report a microfluidic device that utilizes the dielectrophoresis phenomenon to synchronize cells by exploiting the relationship between the cells volume and its phase in the cell cycle. The dielectrophoresis activated cell synchronizer (DACSync) device accepts an asynchronous mixture of cells at the inlet, fractionates the cell populations according to the cell-cycle phase (G1/S and G2/M), and elutes them through different outlets. The device is gentle and efficient; it utilizes electric fields that are 1–2 orders of magnitude below those used in electroporation and enriches asynchronous tumor cells in the G1 phase to 96% in one round of sorting, in a continuous flow manner at a throughput of 2 × 105 cells per hour per microchannel. This work illustrates the feasibility of using laminar flow and electrokinetic forces for the efficient, noninvasive separation of living cells.

Multitarget Dielectrophoresis Activated Cell Sorter

The ability to rapidly and efficiently isolate specific viruses, bacteria, or mammalian cells from complex mixtures lies at the heart of biomedical applications ranging from in vitro diagnostics to cell transplantation therapies. Unfortunately, many current selection methods for cell separation, such as magnetic activated cell sorting (MACS), only allow the binary separation of target cells that have been labeled via a single parameter (e.g., magnetization). This limitation makes it challenging to simultaneously enrich multiple, distinct target cell types from a multicomponent sample. We describe here a novel approach to specifically label multiple cell types with unique synthetic dielectrophoretic tags that modulate the complex permittivities of the labeled cells, allowing them to be sorted with high purity using the multitarget dielectrophoresis activated cell sorter (MT-DACS) chip. Here we describe the underlying physics and design of the MT-DACS microfluidic device and demonstrate approximately 1000-fold enrichment of multiple bacterial target cell types in a single-pass separation.

Rapid, Affordable, and Point-of-Care Water Monitoring Via a Microfluidic DNA Sensor and a Mobile Interface for Global Health

Contaminated water is a serious concern in many developing countries with severe health consequences particularly for children. Current methods for monitoring waterborne pathogens are often time consuming, expensive, and labor intensive, making them not suitable for these regions. Electrochemical detection in a microfluidic platform offers many advantages such as portability, minimal use of instrumentation, and easy integration with electronics. In many parts of the world, however, the required equipment for pathogen detection through electrochemical sensors is either not available or insufficiently portable, and operators may not be trained to use these sensors and interpret results, ultimately preventing its wide adoption. Counterintuitively, these same regions often have an extensive mobile phone infrastructure, suggesting the possibility of integrating electrochemical detection of bacterial pathogens with a mobile platform. Toward a solution to water quality interventions, we demonstrate a microfluidic electrochemical sensor combined with a mobile interface that detects the sequences from bacterial pathogens, suitable for rapid, affordable, and point-of-care water monitoring. We employ the transduction of DNA hybridization into a readily detectable electric signal by means of a conformational change of DNA stem-loop structure. Using this platform, we successfully demonstrate the detection of as low as 100 nM E. coli sequences and the automatic interpretation and mapping of the detection results via a mobile application.

Development of low-cost plastic microfluidic sensors toward rapid and point-of-use detection of arsenic in drinking water for global health

The difficulty of detecting small quantities of arsenic in water currently threatens the health of millions of people worldwide, as long-term exposure to arsenic has been associated with both cancerous and noncancerous health risks. Existing technologies make it possible to very accurately quantify arsenic levels in water; however the expense, extensive training, and off-site analysis required by these methods impede wide scale-use. Electrochemical detection in a microfluidic platform offers many advantages, such as portability, minimal use of instrumentation, and ready integration with electronics. Toward a solution to water quality interventions, we have demonstrated an affordable and point-of-use microfluidic platform capable of detecting trace amounts of arsenic in groundwater samples. Our electrochemical sensor utilizes a three-electrode system with carbon, silver, and silver/silver chloride ink electrodes printed onto a disposable plastic substrate. A small water sample is applied to the electrodes and the current response is quickly captured, returning quantitative information to the user, which alleviates the lag times and imprecise colorimetric assays that encumber current arsenic detection systems.

Low-power, self-contained, reciprocating micropump through electrolysis and catalyst-driven recombination toward drug delivery applications

Implantable pumps have allowed for substantial improvements in health and are a developing discipline in biomedical engineering, with applications in drug delivery, fluid removal, and research [1-4]. Towards this end, we here propose a novel electrolytic micropump utilizing a platinum based catalyst for cyclic operation. This pump design offers advantages in terms of low power consumption, high reliability, precise flow rates, and simple addition of external micro-controllers. Our system leverages electrolysis of water followed by catalyst-driven recombination of electrolytic gases to achieve a reciprocating motion of a membrane that leads to cyclic dispensing of drug fluids, with a performance rate of approximately 0.3μL/min per mA.

Detection of bacterial pathogens through microfluidic DNA sensors and mobile interface toward rapid, affordable, and point-of-care water monitoring

Deteriorating water quality is a serious concern in many developing countries, with severe health consequences especially for children. However, current methods for monitoring waterborne pathogens are often time-consuming, expensive, and labor intensive, which makes them challenging to be implemented in these regions. Toward a solution to this problem, we have demonstrated an electrochemical sensor combined with mobile interface that detects bacterial pathogens suitable for rapid, affordable, and point-of-care water monitoring. The sensor and its mobile interface we developed can be implemented to a wide range of diagnostics. As a proof-of-principle, we successfully detected of E. coli sequences, and mapped the detection results via mobile application.

Electrochemical detection of arsenic via a microfluidic sensor and mobile interface towards affordable, rapid, and point-of-use water monitoring

Arsenic contamination of groundwater presents a major obstacle to the development of water infrastructure in developing countries, with severe long-term health consequences. Current solutions for arsenic testing range from simple colorimetric assays to sophisticated laboratory tests. Colorimetric kits are simple and low-cost, yet these types of tests generally suffer from a lack of precision and use toxic chemicals as test reagents while laboratory-based techniques, such as mass spectrometry, are accurate but considerably more expensive, requiring off-site analysis of samples. Electrochemical detection in a microfluidic platform offers many advantages, such as portability, minimal use of instrumentation, and ready integration with electronics. Toward a solution to water quality interventions, we have demonstrated an electrochemical sensor combined with mobile interface that detects arsenic suitable for rapid, affordable, and point-of-care water monitoring. Using this platform, we successfully demonstrate the detection of arsenic and the automatic interpretation and mapping of the detection results via a mobile application. We expect such a platform for diagnostics via mobile phone with automated test interpretation and mapping to provide an indispensable tool, especially in rural areas where the needs are the greatest, but the lack of laboratory facilities and trained personnel is a real obstacle.

Mobile urinalysis for maternal screening: Frugal medical screening solution and patient database to aid in prenatal healthcare for expecting mothers in the developing world

Pregnant women in the developing world are often denied the level of healthcare that is needed to prepare them for successful deliveries. Often this inequality of service is due to high costs of medical care, the remote location of patients, and the infrequency of medical visits. We have created a mobile application and added a secure light box that will allow a low-cost implementation of urinalysis tests for these women. These tests can help in detecting warning signs for common health risks early in the pregnancy. Our application uses the camera from a mobile device to digitize the colors within the urinalysis test strip. It then compares the colors obtained with baseline colors to identify chemical levels in the urine. The applications interface displays the test results and keeps track of each patients test history. Through detection of certain chemical levels at an earlier time, there is a higher chance for intervention and, therefore, for successful pregnancies. By decentralizing access to preventative healthcare, this solution has the potential to increase the rate of successful pregnancies among women from traditionally underserved communities.

Affordable, rapid, electrochemical nitrate detection towards point-of-use water quality monitoring

Nitrate contamination of groundwater presents a major public health problem in developing countries. Long-term exposure to nitrate causes Blue Baby Syndrome, a leading cause of infant mortality, and various cancers in adults. Spectroscopic nitrate detection methods, while sensitive and accurate, are prohibitively expensive, time consuming and not available at the point of use. Electrochemical detection methods are poised to offer accurate point of use measurements, but so far these methods require expensive modified electrodes and are not commercially available. To aid in water quality interventions, we have demonstrated a low-cost, microfluidic, electrochemical sensor capable of rapid and affordable nitrate detection at the point of use. This platform for water quality testing could serve as a crucial public health tool, especially in rural areas that lack the technical and human resources to adequately monitor water quality.