Ling-Yi Ke

3D lobule-mimetic chip via positive Dielectrophoresis force with sinusoidal spacing poly (ethylene glycol)-diacrylate microwalls

In vitro culture and patterning of living cells to form a ordered 3D tissue is a rapidly developing technique with its applications in drug testing, co-culture studies, generating in vitro models of disease and other fields of biotechnology. This paper reports a 3D lobule-mimetic chip where in a three-dimensional lobule is constructed by using positive DEP (Dielectrophoresis) force. Positive DEP force was utilized to attract, adhere and pattern the cells on the surface of poly (ethylene glycol)-diacrylate (PEG-DA). PEG-DA-based check valve and valveless holes were designed to control the distribution of cells. A 3D lobule-mimetic chip is observed depend on this geometry microstructure and the novel cell manipulation method.

A double trapped single cell contact and interaction system via movable poly (ethylene glycol) diacrylate (PEG-DA) microstructure for immune analysis

Some subsets of immune cells execute their missions depending on cell contact and interaction, like natural killer cell and cytotoxic T lymphocyte. To understand the movement exhibited by cellular aggregates, we must understand how the local interactions between moving cells affect the collective motion. In this paper, we demonstrated a double trapped single cell chip by positive dielectrophoresis (pDEP) force with the movable poly (ethylene glycol) diacrylate (PEG-DA) for cell-cell contact microenvironment. In our design, such as S-shape channel, L-shaped double-lock and /-shaped double-lock, we could evaluate the NK cell activity in single cell level. Based on our data, we provided an easily-performed method for study the interaction of immune cells.

Cryogenic frozen device for hepatocyte culture and responses

In clinical medicine, freezing treatment has been applied to patients for years. However, the combination of the micro/nano biochip (or Lab Chip) techniques and cryogenic frozen techniques were seldom proposed in the past. This paper reports a cryogenic frozen apparatus for the study of microfluidic liver tissue mimic hepatic cords responses on three dimension hepatocyte culture chip. We designed the micro-cylinder about the height of 85 micrometer for loading hepatocyte to form three dimension tissue-mimic structures. The liver is organized into lobules which take the shape of polygonal prisms. Each lobule is typically hexagonal in cross section and is centered on the central vein. The bulk of the lobule consists of hepatocytes which are arranged into hepatic cords that are separated by sinusoid space. In liver function testing, the albumin secretion was affected 12% by freezing the hepatocyte ten minutes.

A multifunctional embryos manipulative microfluidic chip with dynamic flow resistance trapping and CO-culture with stromal cells

In order to optimize the quality of embryos culture, more factors are used to improve the quality of embryos. This microfluidic device integrates the various functions, such as the trapping mechanism of dynamic flow resistance, and co-culture embryos with human stromal cells providing the growth factors. For the main function, embryos can be manipulated by fluidic field in the G-type co-culture chamber (GCC), which can make the embryos grow better by keeping them moving when co-culturing. Its expected that the successful rate of embryos development and the quality can be improved by constructing the suitable environment to provide the physical stimulus for the embryos.

Four-leaf-clover-shaped immune response chip by using optoelectronic tweezers force

To study the immune system, the natural killer (NK) cell and target cell needs to contact for cell-cell interaction. Therefore, an optoelectronic tweezers (OET) complex optofluidic and four-leaf-clover-shaped (FLCS) microwells, multilayered platform was designed and fabricated to increase interaction. In this study, a novel method uses OET to attract immune cell into the dead zone. The proposed design creates a dynamic observation area with slower flow velocity enabling precise capture of immune cell into the microwells without harm, matching the simulation. Through a simple method, the preliminary data of NK cell and target cell interaction is obtained within 4 hours.

Using magnetic marked PEGDA-based cell sheets for three dimensional lobule-mimicking chip

The formation and regeneration of tissue are the result of intricate temporal and spatial coordination of numerous individual cell fate processes. It is regulated not only by cell autonomous processes but also by extracellular microenvironmental stimuli. In this study, we propose lobule-mimicking culture chips by using magnetic-mark poly (ethylene glycol) diacrylate (PEGDA)-based cell sheets (MP cell sheets). It consists of four cell sheet chambers and one stacking chamber. MP cell sheets were formed by UV light two times. Using magnetic field to manipulate MP cell sheets moving and rotating. Finally, we had stacked MP cell sheets to achieve lobule-mimetic regeneration.

Using gelatin methacrylate covering and dielectrophoresis force manipulating for lobule-mimicking culture chip in vitro

In vivo, tissue morphology pays an important role in cell single transferring and tissue function increasing. However, maintaining the mimetic cell culture microenvironment in microfluidic chip, several stresses which break the membrane of cells and damage the pattern of the tissue. In the paper, we demonstrate lobule-mimicking culture chip by using gelatin methacrylate (GelMA) covering and dielectrophoresis (DEP) force manipulating. GelMA is a photocrosslinked biocompatible material. The hydrogel material was used in chip for three purposes: precluding the damage between cells or tissue, providing a biological scaffold to keep cell growth, and supplying the nutrient to cells in diffusible situation.

Difference proportional cell contact platform for 3D hepatocyte culture

This paper reports a difference proportional cell contact platform for three dimension hepatocyte culture. We designed the cell wires about the width of 25 micrometer by dielectrophoresis for difference contact area. The platform was consisted of two dimensional cell contact chambers and three dimensional liver tissue chambers by dielectrophoresis pattern method and microfluidic channel design. For cell contact chambers, we used dielectrophoresis pattern method to make difference contact area for difference proportional cell communication. For liver tissue chambers, we used the UV-initiated solution of the poly (ethylene glycol)-diacrylate (PEG-DA) had been exposed to form microwells to pattern three dimension lobule-mimetic structure liver tissue in vitro. HepG2 cells were loading with three dimensional PEG-DA-dased micro-structures for artificial lobule pattern. Finally, we showed liver functional albumin testing. The albumin secretion of liver pattern chambers with HMEC-1 and C2C12 co-culture communication was 34% higher than the albumin secretion of liver chip without cells communication.

PEGDA-based photocrosslinking platform for real time cell trapping

Poly (ethylene glycol)-diacrylate (PEG-DA) is a commonly used material in tissue engineering. It is cross-linking via UV-initiated photopolymerization to form the PEG-DA microstructures. This paper reports the fabrication of capillary PEG-DA architectures on photopolymerizable hydrogel characteristic. In the UV-initiated photopolymerization, oxygen can damage the photopolymerization reaction that to from microinterstices. In PDMS-based chip, a little oxygen in PDMS material is stored in PEG-DA material. By the way, we designed PEGDA-based V-shape microbarriers to trapped HMEC-1 cell for another biotechnology. For V-shaped microbarriers, we used the solution of the PEG-DA had been exposed to form V-shaped barriers by mask pattern. Cell trapping array platform was used for understanding fundamental cell studies which are cell-cell interactions and cell responses, such as hydrodynamic trapping system.

Microfluidic circulatory system for the raise of liver urea assay

In this research, we propose an in vitro liver circulatory system via the concept of cell pattern technology and microfluidic system. Liver lobule structure in our body consisted of several blood vessel and hepatic tissue. The fluid direction of blood would get in from hepatic portal vein, liver lobule tissue to the hepatic central vein. Hence, in order to mimic the liver circular system in vitro, a connected microchannel system is proposed in this research. This connected system consisted of three parts of channel design, blood vessel chamber, Lobule-flow-mimic channel and liver tissue chamber. Liver circulatory system chip is consisted of blood vessel chamber and liver tissue chamber via dielectrophoresis pattern method and microfluidic channel design.