Jungwook Park

MEMS oxygen transporter to treat retinal ischemia

For the first time, a paradigm shift in the treatment of retinal ischemia is proposed: providing localized supplemental oxygen to the ischemic tissue via an implanted MEMS device. A passive MEMS oxygen transporter is designed, built and tested in both artificial eye models and porcine cadaver eyes to confirm various hypotheses. The finite element modeling results predict that the proposed approach can treat complete retinal ischemia.

Flexible MEA for adult zebrafish ECG recording covering both ventricle and atrium

This paper presents a flexible parylene micro-electrode-array (MEA) that records Electrocardiograms (ECG) from the Zebrafish heart in-vivo, covering both the ventricle and atrium area. ECG is a powerful tool for monitoring the heart activity. While ECG technology for human has been well established, this is not true for zebrafish. Our previous work demonstrated baseline ECG recording from zebrafish using MEMS MEAs [1, 2]. However, due to the body structure and small size of the zebrafish (e.g., the heart is roughly 1mm in size and its atrium is buried deep in the thoracic cavity, Fig.1b.), all zebrafish ECGs to date were only recorded from the ventricular side, making it easy to miss important electrophysiological signals from the atrium. To our knowledge, ECG from the atrial angles in Zebrafish has not yet been demonstrated. This work describes a flexible MEA implant (i.e., specially designed according to zebrafish heart anatomy) that records from both the ventricular and the atrial angles. Furthermore, to demonstrate that this device is useful for heart regeneration monitoring, our work also includes ECG recording before and after laser damage on the ventricle (532nm green light, 32mJ/mm2, 20mJ total). This chosen energy level of laser pulse is first calibrated using ablated heart histology by EthD-1 florescence staining. The post injury ECG data clearly show ST-wave depression, an indication of ventricular abnormal repolarization state. In addition, repeated missing T-wave is observed from the channels recorded from the atrial angles, which indicate abnormalities in atrial physiology. A hypothesis is that since absorption coefficient of 532nm light in body tissue is rather low, the laser beam penetrated deeply in the heart and created damage deep in the atrium as well as the ventricle. The MEA presented here shows potential for an effective tool to study long-term adult zebrafish heart development and regeneration.

Isolation of circulating tumor cells by a magnesium-embedded filter

Circulating tumor cells (CTCs) are rare cancer cells that are shed by tumors into the bloodstream and that can be valuable biomarkers for various types of cancers. However, CTCs captured on the filter could not be released easily using the existing CTC analysis platforms based on size. To address this limitation, we have developed a novel magnesium (Mg)-embedded cell filter for capture, release and isolation of CTCs. The CTC-filter consists of a thin Ebeam-deposited Mg layer embedded between two parylene-C (PA-C) layers with designed slots for filtration and CTC capture. Thin Mg film has proved highly biocompatible and can be etched in saline, PBS and Dulbeccos modified eagle medium (DMEM) etc, properties that are of great benefit to help dissociate the filter and thus release the cells. The finite element method (FEM) analysis was performed on the Mg etching process in DMEM for the structure design. After the filtration process, the filter was submerged in DMEM to facilitate Mg etching. The top PA-C filter pieces break apart from the bottom after Mg completely dissolves, enabling captured CTCs to detach. The released CTC can be easily aspirated into a micropipette for further analysis. Thus, the Mg-embedded cell filter provides a new and effective approach for CTCs isolation from the filter, making this a promising new strategy for cancer detection.

Thin-film magnesium as a sacrificial and biodegradable material

This work reports the study of ebeam-deposited thin-film magnesium (Mg) as a sacrificial and a biodegradable material. We have tested etchants including diluted hydrochloric acid (HCl), saline, and culture medium. Both vertical etching method and channel undercut method are used to characterize the Mg etching properties. The initial results confirm that thin-film Mg is a promising dual sacrificial and biodegradable material. In addition, an etching model, which fits accurately the etching length vs. time over a wide range of HCl concentrations (0.02-1M) is developed. This model is based on diffusion and a combined first-and-second order chemical reaction mechanism.

Continuous monitoring of insulin attachment kinetics on photothermally actuated microcantilever biosensor

This study presents a method for monitoring kinetics of biological interaction using photothermally-actuated microcantilevers resonating in liquid. The surface of the cantilever was functionalized with anti-insulin-antibody to monitor insulin. By varying the insulin concentration, different reaction kinetics were observed in real time by monitoring the resonance frequency shift (Δfr) of the MEMS resonator. We found that fast but weak absorption was dominant at high insulin concentration while slow but strong antigen-antibody binding is predominant at low insulin concentration.

Magnesium-embedded live cell filter for CTC isolation

This paper reports a novel Magnesium-embedded cell filter for Circulating Tumor Cell (CTC) capture, release and isolation. The new and novel feature is the use of thin-film Mg to release the captured CTCs based on the fact that any Cl- containing culture medium can readily etch Mg away [1]. The releasing and the isolation of each individual CTC are demonstrated here. After filtration process, the filter is submerged in PBS to facilitate Mg etching. The top PA-C filter pieces break apart from the bottom after Mg completely dissolves, enabling captured CTC cells to detach from the filter. The released CTC can then be easily aspirated into a micropipette, and then for further, such as, DNA mutation analysis.

Flexible neurocage array for live neural network study

A flexible multi-electrode-array (MEA) with parylene-C (PA-C) cages on PA-C substrate for neural network study in vitro is presented here. 8×8 cage arrays were fabricated on a 10-μm-thick PA-C film. For our use, the array was glued on a 100μm-thick glass substrate for ease of handling. Each cage is to trap an individual neuron to force a close proximity of the neuron to an embedded electrode inside the cage for stimulation and recording. In addition, each neurocage has six tunnels emanating from the cage to allow axons and dendrites to grow outward and form synapses with other trapped neurons. The Electrode inside each neurocage can then be used to stimulate and/or record electrical activity from the trapped cell at any given time. Why thin and flexible? From our previous work, it is learned that manually loading neuron one-by-one into the cage is time-consuming. We then propose to use laser tweezer to do the cell loading from the backside of the array. To facilitate laser tweezer neuron loading, the neurocage array must be transparent and thin. On the other hand, device flexibility facilitates a high-yield fabrication, easy singulation and attachment to almost any substrate for use.

MEMS for single-islet electroisletogram

This paper reports the first MEMS device designed for in vitro measuring of electroisletogram (EIG) of individual rat islets. Using vacuum to hold an islet in proximity to a microelectrode, strong EIG signals in millivolt range are obtained, while the noise is about 100μV pk-pk. This work proves the feasibility of using MEMS and EIG for high-throughput screening, in contrast to patch-clamp measurements, of islets for transplantation to treat diabetes.

Wearable flexible micro electrode for adult zebrafish long term ecgmonitoring

During the last decade, close resemblance between the zebrafish heart and human heart physiology has been discovered [1] andzebrafish (Danio rerio) has become an emerging animal model for studying side effects developmental drugs may impose on the heart [2][3]. More interestingly, contrary to human heart the zebrafish heart has a remarkable ability to “regenerate” after severe injury [4], making it also a popular model for studies of regenerative medicine. On the other hand, Electrocardiogram (ECG) is a widely used tool to monitor the physiological changes of the zebrafish heart. However, due to its in-water habitat, a long term ECG monitoring solution, although very much needed, was not present. All published adult zebrafish ECG recorded to this date have been done acutely with anesthetized fish. This work presents, for the first time a wearable flexible parylene (PA) micro-electrode that monitors the Adult Zebrafish ECG long term. We show here the design, fabrication and testing of the flexible electrode along with a micro-molded ultra-soft, density adjusted silicone jacket, allowing ECG recording to be carried under water, in the fishs natural habitat with no need for anesthesia.

Novel type of microcantielver biosesor resonating at the interface between liquid and air

We developed a new type of a microcantilever biosensor resonating at the interface between air and liquid. The cantilever sensor has advantages in high signal-to-noise ratio (SNR) and high quality factor (Q-factor) for detecting bio-reactions because liquid damping acts on only one-side, and because there is no obstacle between detection, excitation lasers and the cantilever. (Fig. 1 (c)) Using the cantilever integrated with a microchannel and phase locked loop detection, we measured adsorption reaction kinetics of carboxylated microspheres in real time for three different concentrations.