Chiwan Koo

Manipulating Liquid Metal Droplets in Microfluidic Channels With Minimized Skin Residues Toward Tunable RF Applications

A nontoxic liquid metal, such as eutectic gallium-indium (EGaIn) alloy, has been used to develop tunable radio frequency (RF) components, such as antennas, inductors, or capacitors, for enabling large tunable range, better linearity, and low loss, using fluidic displacement of the liquid metal. However, EGaIn residue, due to its fast oxidation, limits multiple movement of the EGaIn in the reconfigurable RF components. This paper focuses on the use of surfactants, carrier liquids, and microchannel coating materials that minimize EGaIn fragmentation and EGaIn residues on poly(dimethylsiloxane) (PDMS)-based microfluidic channels during repeated actuation of an EGaIn plug. Using a combination of carrier liquids and microchannel coating materials to minimize EGaIn from leaving residues on the PDMS microfluidic channel, a microstrip transmission line switch as a proof-of-concept reconfigurable RF application using the EGaIn plug is demonstrated. It is switched ON<;4 dB and OFF with a loss of <;18 dB over the frequency range between 4 and 15 GHz.

Microfluidic electro-sonoporation: a multi-modal cell poration methodology through simultaneous application of electric field and ultrasonic wave

A microfluidic device that simultaneously applies the conditions required for microelectroporation and microsonoporation in a flow-through scheme toward high-efficiency and high-throughput molecular delivery into mammalian cells is presented. This multi-modal poration microdevice using simultaneous application of electric field and ultrasonic wave was realized by a three-dimensional (3D) microelectrode scheme where the electrodes function as both electroporation electrodes and cell flow channel so that acoustic wave can be applied perpendicular to the electric field simultaneously to cells flowing through the microfluidic channel. This 3D microelectrode configuration also allows a uniform electric field to be applied while making the device compatible with fluorescent microscopy. It is hypothesized that the simultaneous application of two different fields (electric field and acoustic wave) in perpendicular directions allows formation of transient pores along two axes of the cell membrane at reduced poration intensities, hence maximizing the delivery efficiency while minimizing cell death. The microfluidic electro-sonoporation system was characterized by delivering small molecules into mammalian cells, and showed average poration efficiency of 95.6% and cell viability of 97.3%. This proof of concept result shows that by combining electroporation and sonoporation together, significant improvement in molecule delivery efficiency could be achieved while maintaining high cell viability compared to electroporation or sonoporation alone. The microfluidic electro-sonoporation device presented here is, to the best of our knowledge, the first multi-modal cell poration device using simultaneous application of electric field and ultrasonic wave. This new multi-modal cell poration strategy and system is expected to have broad applications in delivery of small molecule therapeutics and ultimately in large molecule delivery such as gene transfection applications where high delivery efficiency and high viability are crucial.

Development of a real-time microchip PCR system for portable plant disease diagnosis.

Rapid and accurate detection of plant pathogens in the field is crucial to prevent the proliferation of infected crops. Polymerase chain reaction (PCR) process is the most reliable and accepted method for plant pathogen diagnosis, however current conventional PCR machines are not portable and require additional post-processing steps to detect the amplified DNA (amplicon) of pathogens. Real-time PCR can directly quantify the amplicon during the DNA amplification without the need for post processing, thus more suitable for field operations, however still takes time and require large instruments that are costly and not portable. Microchip PCR systems have emerged in the past decade to miniaturize conventional PCR systems and to reduce operation time and cost. Real-time microchip PCR systems have also emerged, but unfortunately all reported portable real-time microchip PCR systems require various auxiliary instruments. Here we present a stand-alone real-time microchip PCR system composed of a PCR reaction chamber microchip with integrated thin-film heater, a compact fluorescence detector to detect amplified DNA, a microcontroller to control the entire thermocycling operation with data acquisition capability, and a battery. The entire system is 25×16×8 cm3 in size and 843 g in weight. The disposable microchip requires only 8-µl sample volume and a single PCR run consumes 110 mAh of power. A DNA extraction protocol, notably without the use of liquid nitrogen, chemicals, and other large lab equipment, was developed for field operations. The developed real-time microchip PCR system and the DNA extraction protocol were used to successfully detect six different fungal and bacterial plant pathogens with 100% success rate to a detection limit of 5 ng/8 µl sample.

Ratiometric temperature imaging using environment-insensitive luminescence of Mn-doped core–shell nanocrystals

We report a ratiometric temperature imaging method based on Mn luminescence from Mn-doped CdS-ZnS nanocrystals (NCs) with controlled doping location, which is designed to exhibit strong temperature dependence of the spectral lineshape while being insensitive to the surrounding chemical environment. Ratiometric thermometry on the Mn luminescence spectrum was performed by using Mn-doped CdS-ZnS core-shell NCs that have a large local lattice strain on the Mn site, which results in the enhanced temperature dependence of the bandwidth and peak position. The Mn luminescence spectral lineshape is highly robust with respect to the change in the polarity, phase and pH of the surrounding medium and aggregation of the NCs, showing great potential in temperature imaging under chemically heterogeneous environment. The temperature sensitivity (ΔIR/IR = 0.5%/K at 293 K, IR = intensity ratio at two different wavelengths) is highly linear in a wide range of temperatures from cryogenic to above-ambient temperatures. We demonstrate the surface temperature imaging of a cryo-cooling device showing a temperature variation of >200 K by imaging the luminescence of the NC film formed by simple spin coating, taking advantage of the environment-insensitive luminescence.

A Microfluidically Cryocooled Spiral Microcoil With Inductive Coupling for MR Microscopy

Magnetic resonance (MR) microscopy typically employs microcoils for enhanced local signal-to-noise ratio (SNR). Planar (surface) microcoils, in particular, offer the potential to be configured into array elements as well as to enable the imaging of extremely small samples because of the uniformity and precision provided by microfabrication techniques. Microcoils, in general, however, are copper-loss dominant, and cryocooling methods have been successfully used to improve the SNR. Cryocooling of the matching network elements, in addition to the coil itself, has shown to provide the most improvement, but can be challenging with respect to cryostat requirements, cabling, and tuning. Here we present the development of a microfluidically cryocooled spiral microcoil with integrated microfabricated parallel plate capacitors, allowing for localized cryocooling of both the microcoil and the on-chip resonating capacitor to increase the SNR while keeping the sample-to-coil distance within the most sensitive imaging range of the microcoil. Inductive coupling was used instead of a direct transmission line connection to eliminate the physical connection between the microcoil and the tuning network so that a single cryocooling microfluidic channel could enclose both the microcoil and the on-chip capacitor with minimum loss in cooling capacity. Comparisons between the cooled and uncooled cases were made via Q-factor measurements and agreed well with the theoretically achievable improvement: the cooled integrated capacitor coil with inductive coupling achieved a factor of 2.6 improvement in Q-factor over a reference coil conventionally matched and tuned with high- Q varactors and capacitively connected to the transmission line.

A magnetic resonance (MR) microscopy system using a microfluidically cryo-cooled planar coil

We present the development of a microfluidically cryo-cooled planar coil for magnetic resonance (MR) microscopy. Cryogenically cooling radiofrequency (RF) coils for magnetic resonance imaging (MRI) can improve the signal to noise ratio (SNR) of the experiment. Conventional cryostats typically use a vacuum gap to keep samples to be imaged, especially biological samples, at or near room temperature during cryo-cooling. This limits how close a cryo-cooled coil can be placed to the sample. At the same time, a small coil-to-sample distance significantly improves the MR imaging capability due to the limited imaging depth of planar MR microcoils. These two conflicting requirements pose challenges to the use of cryo-cooling in MR microcoils. The use of a microfluidic based cryostat for localized cryo-cooling of MR microcoils is a step towards eliminating these constraints. The system presented here consists of planar receive-only coils with integrated cryo-cooling microfluidic channels underneath, and an imaging surface on top of the planar coils separated by a thin nitrogen gas gap. Polymer microfluidic channel structures fabricated through soft lithography processes were used to flow liquid nitrogen under the coils in order to cryo-cool the planar coils to liquid nitrogen temperature (-196 °C). Two unique features of the cryo-cooling system minimize the distance between the coil and the sample: (1) the small dimension of the polymer microfluidic channel enables localized cooling of the planar coils, while minimizing thermal effects on the nearby imaging surface. (2) The imaging surface is separated from the cryo-cooled planar coil by a thin gap through which nitrogen gas flows to thermally insulate the imaging surface, keeping it above 0 °C and preventing potential damage to biological samples. The localized cooling effect was validated by simulations, bench testing, and MR imaging experiments. Using this cryo-cooled planar coil system inside a 4.7 Tesla MR system resulted in an average image SNR enhancement of 1.47 ± 0.11 times relative to similar room-temperature coils.

A Microchip for High-Throughput Axon Growth Drug Screening

It has been recently known that not only the presence of inhibitory molecules associated with myelin but also the reduced growth capability of the axons limit mature central nervous system (CNS) axonal regeneration after injury. Conventional axon growth studies are typically conducted using multi-well cell culture plates that are very difficult to use for investigating localized effects of drugs and limited to low throughput. Unfortunately, there is currently no other in vitro tool that allows investigating localized axonal responses to biomolecules in high-throughput for screening potential drugs that might promote axonal growth. We have developed a compartmentalized neuron culture platform enabling localized biomolecular treatments in parallel to axons that are physically and fluidically isolated from their neuronal somata. The 24 axon compartments in the developed platform are designed to perform four sets of six different localized biomolecular treatments simultaneously on a single device. In addition, the novel microfluidic configuration allows culture medium of 24 axon compartments to be replenished altogether by a single aspiration process, making high-throughput drug screening a reality.

Particle velocity measurements with macroscopic fluorescence imaging in lymph tissue mimicking microfluidic phantoms

Ultrasound poroelastography can quantify structural and mechanical properties of tissues such as stiffness, compressibility, and fluid flow rate. This novel ultrasound technique is being explored to detect tissue changes associated with lymphatic disease. We have constructed a macroscopic fluorescence imaging system to validate ultrasonic fluid flow measurements and to provide high resolution imaging of microfluidic phantoms. The optical imaging system is composed of a white light source, excitation and emission filters, and a camera with a zoom lens. The field of view can be adjusted from 100 mm x 75 mm to 10 mm x 7.5 mm. The microfluidic device is made of polydimethylsiloxane (PDMS) and has 9 channels, each 40 μm deep with widths ranging from 30 μm to 200 μm. A syringe pump was used to propel water containing 15 μm diameter fluorescent microspheres through the microchannels, with flow rates ranging from 0.5 μl/min to 10 μl/min. Video was captured at a rate of 25 frames/sec. The velocity of the microspheres in the microchannels was calculated using an algorithm that tracked the movement of the fluorescent microspheres. The imaging system was able to measure particle velocities ranging from 0.2 mm/sec to 10 mm/sec. The range of flow velocities of interest in lymph vessels is between 1 mm/sec to 10 mm/sec; therefore our imaging system is sufficient to measure particle velocity in phantoms modeling lymphatic flow.

Acoustic standing wave based microsystem for low-concentration oil detection and separation

Detection and quantification of extremely small amount of oil on site and at low cost has broad applications in environmental monitoring, both in oil spills as well as in routine marine/costal ecosystem monitoring. For example, dispersed oil, generated through the use of chemical dispersants in oil spills to break up oil slick into small droplets so that they can be rapidly diluted in 3D space are the greatest concern and poses the most challenges in detection. Fluorometry is the current standard method, however is bulky and expensive, limiting its wide deployment in the field. Here we demonstrate for the first time the development of an acoustic standing wave based microfluidic platform capable of processing large amount of liquid samples from which dispersed oil can be concentrated and separated to a detectable level by acoustophoretic force. The microfluidic platform consists of a recirculation channel structure into which dispersed oil droplets can be continuously separated from the main sample flow s...

An integrated microfluidic cryo-cooled planar coil system for magnetic resonance imaging (MRI)

An integrated microfluidic cryo-cooled planar radiofrequency (RF) coil system has been developed to enhance the signal to noise ratio (SNR) of high resolution and ultra-fast magnetic resonance imaging (MRI) experiments. The developed system can cool MR planar coils to liquid nitrogen temperature (−196 °C) without freezing the target samples on the imaging surface, thereby maintaining minimal distance between the coils and the samples. The planar coils were fabricated on a 0.5 mm thick poly(methyl methacrylate) (PMMA) substrate by using microfabrication technologies with a poly (dimethylsiloxane) (PDMS) microfluidic channel for liquid nitrogen cooling. The average signal to noise ratio (SNR) enhancement measured with imaging was 1.51 ± 0.09 times.