Zhaochu Yang

A smart fully integrated micromachined separator with soft magnetic micro-pillar arrays for cell isolation

A smart fully integrated micromachined separator with soft magnetic micro-pillar arrays has been developed and demonstrated, which can merely employ one independent lab-on-chip to realize cell isolation. The simulation, design, microfabrication and test for the new electromagnetic micro separator were executed. The simulation results of the electromagnetic field in the separator show that special soft magnetic micro-pillar arrays can amplify and redistribute the electromagnetic field generated by the micro-coils. The separator can be equipped with a strong magnetic field to isolate the target cells with a considerably low input current. The micro separator was fabricated by micro-processing technology. An electroplating bath was hired to deposit NiCo/NiFe to fabricate the micro-pillar arrays. An experimental system was set up to verify the function of the micro separator by isolating the lymphocytes, in which the human whole blood mixed with Dynabeads® FlowComp Flexi and monoclonal antibody MHCD2704 was used as the sample. The results show that the electromagnetic micro separator with an extremely low input current can recognize and capture the target lymphocytes with a high efficiency, the separation ratio reaching more than 90% at a lower flow rate. For the electromagnetic micro separator, there is no external magnetizing field required, and there is no extra cooling system because there is less Joule heat generated due to the lower current. The magnetic separator is totally reusable, and it can be used to separate cells or proteins with common antigens.

A mediator embedded micro-immunosensing unit for electrochemical detection on viruses within physiological saline media

To provide a time- and cost-saving alternative to the conventional methods for virus detection in biological media, this work presents an electrochemical micro-immunosensor based on the nickel hexacyanoferrate (NiHCF) redox mediator film coating the interdigitated microelectrodes (IDMEs). By chelation binding with no additional cross-linker, the 6xHis-tagged antibodies were immobilized on a NiHCF film. Secondly, an immunoassay response was enhanced by employing microbeads coated with 6xHis antibody. The electrochemical properties and the stability of the NiHCF film modified IDMEs were evaluated by cyclic voltammetry. The bead-induced impedance variations at the electrode film/electrolyte interface were characterized by electrochemical impedance spectroscopy and verified using FEM simulation. Experiments of virus detection were conducted through targeting the antigens of the vital infectious salmon viruses, such as infectious salmon anaemia virus, infectious pancreatic necrosis virus and salmonid alphavirus subtype 3. The micro-immunosensor exhibited detection limits as low as 10 pg ml−1 and detection sensitivities as high as 57.5 kΩ µM−1 within a physiological saline solution. Tests for multiple antigen–antibody interactions showed good detection specificity, as confirmed by ELISA. By incorporating the microfluidic network, electrochemical impedance micro-immunosensing units can be realized in a fully integrated platform for multiplex virus detection in tissue samples.

Design and optimization of non-clogging counter-flow microconcentrator for enriching epidermoid cervical carcinoma cells

Clogging failure is common for microfilters in living cells concentration; for instance, the CaSki Cell-lines (Epidermoid cervical carcinoma cells) utilizing the flat membrane structure. In order to avoid the clogging, counter-flow concentration units with turbine blade-like micropillar are proposed in microconcentrator design. Due to the unusual geometrical-profiles and extraordinary microfluidic performance, the cells blocking does not occur even at permeate entrances. A counter-flow microconcentrator was designed, with both processing layer and collecting layer arranged in terms of the fractal based honeycomb structure. The device was optimized by coupling Artificial Neuron Network (ANN) and Computational Fluid Dynamics (CFD). The excellent concentration ratio of a final microconcentrator was presented in numerical results.

Power generation from conductive droplet sliding on electret film

Generating electrical power from low frequency vibration to power portable devices is a challenge that potentially can be met by nonresonant electrostatic energy harvesters. We propose a generator employing a conductive droplet sliding on a microfabricated electret film which is sputtered onto an interdigital electrode and charged already during deposition. Droplet motion causes a capacitance variation that is used to generate electric power. A prototype of the fluidic energy harvester demonstrated a peak output power at 0.18 µW with a single droplet having a diameter of 1.2 mm and sliding on a 2 -µm thick electret film.

Electrostatic Energy Harvester Employing Conductive Droplet and Thin-Film Electret

This paper presents detailed investigations on an electrostatic energy harvester using conductive droplet/marble rolling across a charged electret film. Both mercury droplets and ionic liquid marbles were used as the working medium. With a 1.2-mm mercury droplet rolling across the electret film of the prototype, a maximum output power was obtained at 0.18 μW and the peak value of the output voltage was 1.5 V. A semi-empirical model was developed to understand the output waveforms. Applied to the test data, it shows that the transducer short-circuit charge is mainly a function of droplet position in the pattern. Several factors influencing the output performance are discussed. Such droplet-based electrostatic energy harvesters are especially suitable for very low frequency vibration up to a few Hz.

Identification of microfluidic two-phase flow patterns in lab-on-chip devices

This paper presents a feasible solution for a real-time sensing of microfluidic two-phase flow in lab-on-chip devices. A capacitive flow pattern sensor has been realized by employing an interdigital electrode configuration and a thin dielectric film. Three main flow patterns were observed in the microchannel, namely, droplet, short slug, and long slug flows. The output signal from the sensor was a real-time capacitance variation induced by the different flow patterns passing the sensing area. Experimental results give an indication of the flow patterns, due to the profile of capacitance variation. Furthermore, the identification of the flow patterns was achieved by autocorrelation of the capacitance variation and evaluation of a constant, specific for a given flow pattern in terms of linear velocity relation. This two-phase flow pattern sensor has potential to be used with other fluids, as long as they are immiscible and have very distinct dielectric properties.

Interfacial Impedance Sensor Employing Bio-activated Microbeads and NiHCF-Coated Interdigitated Microelectrodes: A Model Analysis

An impedance sensor based on NiHCF-coated interdigitated microelectrodes is presented as a promising solution for ultra-low level pathogen detection. The micro sensor employs micro-sized beads, which are coated with anti-pathogen specific antibodies, to achieve the high-sensitive detection through the amplified variations of the interfacial impedance. The effect of beads on the microelectrodes solution interface and subsequent impedance change were analyzed and demonstrated by fitting the experimental data to an equivalent electrical circuit model.

Fully integrated micro-separator with soft-magnetic micro-pillar arrays for filtrating lymphocytes

A fully integrated micro-separator with soft-magnetic micro-pillar arrays has been developed, which merely employs one independent Lab-On-Chip to realize the lymphocytes isolation from the human whole blood. The simulation, fabrication and experiment are executed to realize this novel microseparator. The simulation results show that, the soft-magnetic micro-pillars array can amplify and redistribute the electromagnetic field generated by the microcoils. The tests certify desirable separation efficiency can be realized using this new separator at low current. No extra cooling system is required for such a micro-separator. This micro-separator can also be used to separate other target cells or particles with the same principle.

Concept and approach of human signal-molecular-profiling database: A pilot study on depression using Lab-on-chips

Signal molecular profiling (SMP) in serum can reveal abundant medical information about the human body. The construction of a human signal-molecular-profiling database (HSMPD) will greatly prompt the research of medical science. However, some challenges hinder the construction of HSMPD. A promising strategy is proposed to provide a convenient way for the establishment of HSMPD. Firstly, a low-cost and high-throughput tool for measuring SMP should be developed and standardized. When the SMP-oriented tools were accepted by most hospitals worldwide, SMP information will be decoded by a cloud-based system and stored into the online database naturally. In the pilot study, an ultrasensitive Lab-on-chips (LOC) device was developed as a specific tool for SMP. Clinical serum samples from 10 women within 4 weeks of giving birth, including 2 patients with postpartum depression were studied by the LOC devices, since accumulating evidence has indicated that hormones and cytokines in patients with mood disorders are abnormal. HSMPD may be applied to diagnose depression in the future. Here, five kinds of signal molecules were quantified on the devices, namely, tumor necrosis factor-alpha (TNF-α), thyroid-stimulating hormone (TSH), interleukin (IL)-2, IL-6 and IL-8. The preliminary results showed that the concentrations of IL-2 and IL-8 in the depression group may be higher than those in the control group, whereas the other kinds of signal molecules did not change significantly. Although the correlations are not enough to induct any diagnostic criterion, the SMP-oriented tool was verified. The results also indicated that the strategy to establish HSMPD is conceivable.

A Novel MEMS Based Infrared Biosensor for Ultra-Sensitive Detection of Waterborne Pathogens

In this paper, a new concept of MEMS based biosensor is presented as a promising solution for the ultra- low level and real time detection of waterborne pathogens. This novel infrared biosensor employs the SiGe/Si quantum well thermistor with a high TCR and low 1/f noise to achieve a high sensitive detection through its resistance change with the absorption of infrared radiation from the dark quencher. Meanwhile, a manufacturing process applying the adhesive wafer bonding is proposed.