Chun-Ping Jen

A Novel Design of Grooved Fibers for Fiber-Optic Localized Plasmon Resonance Biosensors

Bio-molecular recognition is detected by the unique optical properties of self-assembled gold nanoparticles on the unclad portions of an optical fiber whose surfaces have been modified with a receptor. To enhance the performance of the sensing platform, the sensing element is integrated with a microfluidic chip to reduce sample and reagent volume, to shorten response time and analysis time, as well as to increase sensitivity. The main purpose of the present study is to design grooves on the optical fiber for the FO-LPR microfluidic chip and investigate the effect of the groove geometry on the biochemical binding kinetics through simulations. The optical fiber is designed and termed as U-type or D-type based on the shape of the grooves. The numerical results indicate that the design of the D-type fiber exhibits efficient performance on biochemical binding. The grooves designed on the optical fiber also induce chaotic advection to enhance the mixing in the microchannel. The mixing patterns indicate that D-type grooves enhance the mixing more effectively than U-type grooves. D-type fiber with six grooves is the optimum design according to the numerical results. The experimental results show that the D-type fiber could sustain larger elongation than the U-type fiber. Furthermore, this study successfully demonstrates the feasibility of fabricating the grooved optical fibers by the femtosecond laser, and making a transmission-based FO-LPR probe for chemical sensing. The sensor resolution of the sensor implementing the D-type fiber modified by gold nanoparticles was 4.1 × 10−7 RIU, which is much more sensitive than that of U-type optical fiber (1.8 × 10−3 RIU).

Three-dimensional cellular focusing utilizing a combination of insulator-based and metallic dielectrophoresis.

Particle focusing in microfluidic devices is a necessary step in medical applications, such as detection, sorting, counting, and flow cytometry. This study proposes a microdevice that combines insulator-based and metal-electrode dielectrophoresis for the three-dimensional focusing of biological cells. Four insulating structures, which form an X pattern, are employed to confine the electric field in a conducting solution, thereby creating localized field minima in the microchannel. These electrodes, 56-μm-wide at the top and bottom surfaces, are connected to one electric pole of the power source. The electrodes connected to the opposite pole, which are at the sides of the microchannel, have one of three patterns: planar, dual-planar, or three-dimensional. Therefore, low-electric-field regions at the center of the microchannel are generated to restrain the viable HeLa cells with negative dielectrophoretic response. The array of insulating structures aforementioned is used to enhance the performance of confinement. According to numerical simulations, three-dimensional electrodes exhibit the best focusing performance, followed by dual-planar and planar electrodes. Experimental results reveal that increasing the strength of the applied electric field or decreasing the inlet flow rate significantly enhances focusing performance. The smallest width of focusing is 17 μm for an applied voltage and an inlet flow rate of 35 V and 0.5 μl/min, respectively. The effect of the inlet flow rate on focusing is insignificant for an applied voltage of 35 V. The proposed design retains the advantages of insulator-based dielectrophoresis with a relatively low required voltage. Additionally, complicated flow controls are unnecessary for the three-dimensional focusing of cells.

Three‐dimensional focusing of particles using negative dielectrophoretic force in a microfluidic chip with insulating microstructures and dual planar microelectrodes

The focusing of biological and synthetic particles in microfluidic devices is a prerequisite for the construction of microstructured materials, as well as for medical applications. In the present study, a microdevice that can effectively focus particles in three dimensions using a combination of insulator‐based and metal‐electrode dielectrophoresis (DEP) has been designed and fabricated. The DEP force is employed to confine the particles using a negative DEP response. Four insulating microstructures, which form an X‐pattern in the microchannel, were employed to distort the electric field between the insulators in a conducting solution, thereby generating regions with a high electric‐field gradient. Two strips of microelectrodes on the top and bottom surfaces were placed in the middle of the microchannel and connected to an electric pole. Two sets of dual‐planar electrodes connected to the opposite pole were placed at the sides of the microchannel at the top and bottom surfaces. The results of a transient simulation of tracks of polystyrene particles, which was performed using the commercial software package CFD‐ACE+ (ESI Group, France), demonstrate that the three‐dimensional focusing of particles was achieved when the applied voltage was larger than 35u2009V at a frequency of 1u2009MHz. Furthermore, the focusing performance increased with the increased strength of the applied electric field and decreased inlet flow rate. Experiments on particle focusing, employing polystyrene particles 10u2009μm in diameter, were conducted to demonstrate the feasibility of the proposed design; the results agree with the trend predicted by numerical simulations.

Characterizing Esophageal Cancerous Cells at Different Stages Using the Dielectrophoretic Impedance Measurement Method in a Microchip

Analysis of cancerous cells allows us to provide useful information for the early diagnosis of cancer and to monitor treatment progress. An approach based on electrical principles has recently become an attractive technique. This study presents a microdevice that utilizes a dielectrophoretic impedance measurement method for the identification of cancerous cells. The proposed biochip consists of circle-on-line microelectrodes that are patterned using a standard microfabrication processes. A sample of various cell concentrations was introduced in an open-top microchamber. The target cells were collectively concentrated between the microelectrodes using dielectrophoresis manipulation, and their electrical impedance properties were also measured. Different stages of human esophageal squamous cell carcinoma lines could be distinguished. This result is consistent with findings using hyperspectral imaging technology. Moreover, it was observed that the distinguishing characteristics change in response to the progression of cancer cell invasiveness by Raman spectroscopy. The device enables highly efficient cell collection and provides rapid, sensitive, and label-free electrical measurements of cancerous cells.

Three-dimensional cellular focusing utilizing negative dielectrophoretic force generated by dual-planar electrodes

The main purpose of this paper was to numerically design an insulator-based dielectrophoretic microdevice with three-dimensional focusing of biological cells. The cells were introduced into the microchannel and pre-confined hydrodynamically by the funnel-shaped insulating structures close to the inlet. The dielectrophoretic force was employed to confine the cells with a negative dielectrophoretic response. The dual-planar electrodes connected to the opposite pole were designed at the top and bottom surfaces of the microchannel. Four insulating structures, which formed an X-pattern as shown in the microchannel, were employed to squeeze the electric field in a conducting solution, thereby generating high-electric-field regions. The results of numerical simulation indicated apparently that the increase of the electric field applied significantly enhanced the performance of focusing. According to the numerical results, decreasing the inlet velocity could increase the efficiency of focusing. The transient simulation of viable cell tracks also demonstrated that the three-dimensional focusing of particles was successfully achieved. The design proposed herein has no need of complicated flow controls for focusing of cells. The microdevice is easy to operate and integrate into further biomedical applications.

Dielectrophoresis Microfluidic Enrichment Platform with Built-In Capacitive Sensor for Rare Tumor Cell Detection

The manipulation and detection of rare cells are important for many applications in early disease diagnosis and medicine. This study presents a dielectrophoresis (DEP) microfluidic enrichment platform combined with a built-in capacitive sensor for circulating tumor cell detection. The microchip is composed of a lollipop-shaped gold microelectrode structure under a polydimethylsiloxane chamber. A prototype of the device was fabricated using standard micromachining technology. With the proposed device, target cells (in this study, A549 non-small human lung carcinoma and S-180 sarcoma cell lines) are firstly guided toward the center of the working chamber via DEP forces. Then, the target cells are captured by an electrode immobilized by anti-EGFR, which has high affinity toward the target cells. After the cell concentration process, the differential capacitance is read to detect the presence of the target cells. Numerical simulations and measurement experiments were performed to demonstrate the high sensitivity of differential capacitive sensing. The obtained results show high sensitivity for S-180 cell detection (3 mV/cell). The proposed platform is suitable for rapid cancer diagnoses and other metabolic disease applications.

A compact microfluidic chip with integrated impedance biosensor for protein preconcentration and detection

In this study, a low-cost, compact biochip is designed and fabricated for protein detection. Nanofractures formed by self-assembled gold nanoparticles at junction gaps are applied for ion enrichment and depletion to create a trapping zone when electroosmotic flow occurs in microchannels. An impedance measurement module is implemented based on the lock-in amplifier technique to measure the impedance change during antibody growth on the gold electrodes which is caused by trapped proteins in the detection region. The impedance measurement results confirm the presence of trapped proteins. Distinguishable impedance profiles, measured at frequencies in the range of 10-100u2009kHz, for the detection area taken before and after the presence of proteins validate the performance of the proposed system.

An Aptamer-Based Capacitive Sensing Platform for Specific Detection of Lung Carcinoma Cells in the Microfluidic Chip

Improvement of methods for reliable and early diagnosis of the cellular diseases is necessary. A biological selectivity probe, such as an aptamer, is one of the candidate recognition layers that can be used to detect important biomolecules. Lung cancer is currently a typical cause of cancer-related deaths. In this work, an electrical sensing platform is built based on amine-terminated aptamer modified-gold electrodes for the specific, label-free detection of a human lung carcinoma cell line (A549). The microdevice, that includes a coplanar electrodes configuration and a simple microfluidic channel on a glass substrate, is fabricated using standard photolithography and cast molding techniques. A procedure of self-assembly onto the gold surface is proposed. Optical microscope observations and electrical impedance spectroscopy measurements confirm that the fabricated microchip can specifically and effectively identify A549 cells. In the experiments, the capacitance element that is dominant in the change of the impedance is calculated at the appropriate frequency for evaluation of the sensitivity of the biosensor. Therefore, a simple, inexpensive, biocompatible, and selective biosensor that has the potential to detect early-stage lung cancer would be developed.

Dielectrophoresis enrichment with built-in capacitive sensor microfluidic platform for tumor rare cell detection

This paper presents a dielectrophoresis (DEP) enrichment microfluidic platform with built-in antibody-based capacitive sensor for tumor rare cells detection. We take the advantages of the effective DEP actuation, the high selectivity property of antibody for rare cell immobilization, and the high sensitivity of differential capacitive sensing for quantitatively reading out, to produce advanced platform, toward single tumor cell detection for the rapid laboratory tests of cancers diagnoses and other metabolic diseases applications.

A compact exclusion-enrichment microfluidic chip with integrated impedance biosensor for lowconcentration protein detection

This paper presents a design of a compact system for low concentration protein detection based on an effectiveness concentrator which is relied on exclusion-enrichment effect (EEE) and a highly sensitivity lock-in impedance measurement technique. Experiment results suggested that protein concentration of down to sub-nanomolar can be detected by the proposed system.