Applications, techniques, and microfluidic interfacing for nanoscale biosensing

Biosensors based on nanotechnology are rapidly developing and are becoming widespread in the biomedical field and analytical chemistry. For these nanobiosensors to reach their potential, they must be integrated with appropriate packaging techniques, which are usually based on nano/microfluidics. In this review we provide a summary of the latest developments in nanobiosensors with a focus on label-based (fluorescence and nanoparticle) and label-free methods (surface plasmon resonance, micro/nanocantilever, nanowires, and nanopores). An overview on how these sensors interface with nano/microfluidics is then presented and the latest papers in the area summarized.     

AFM-based identification of the dynamic properties of globular proteins: simulation study

Nowadays a mathematical model-based computational approach is getting more attention as an effective tool for understanding the mechanical behaviors of biological systems. To find the mechanical properties of the proteins required to build such a model, this paper investigates a real-time identification method based on an AFM nanomanipulation system. First, an AFM-based bio-characterization system is introduced. Second, a second-order time-varying linear model representing the interaction between an AFM cantilever and globular proteins in a solvent is presented. Finally, we address a real-time estimation method in which the results of AFM experiments are designed to be inputs of the state estimator proposed here. Our attention is restricted to a theoretical feasibility analysis of the proposed methodology. We simply set the mechanical properties of the particular protein such as mass, stiffness, and damping coefficient in the system model prior to running the simulation. Simulation results show very good agreement with the preset properties. We anticipate that the realization of the AFM-based bio-characterization system will also provide an experimental validation of the proposed identification procedure in the future. This methodology can be used to determine a model of protein motion for the purpose of computer simulation and for a real-time modification of protein deformation. This paper was recommended for publication in revised form by Associate Editor Dae-Eun Kim Jungyul Park received the B.S. and M.S. degrees in mechanical design and production engineering from the Seoul National University in 1998 and 2000, respectively and received Ph.D. degree in School of Mechanical & Aerospace Engineering from the Seoul National University, Korea in 2005. He is currently an assistant professor in the mechanical engineering department, Sogang University, in Korea (since 2007). Previously he had worked at the Korea Institute of Science and Technology and at the biomedical engineering department, Johns Hopkins University. His research interests are design, fabrication and analysis of BioMEMS, manipulation, characterization and identification of cells/biomolecules using micro/nano technology, and precise control for micro/nano manipulation.     

Quantitative analysis of the combined effect of substrate rigidity and topographic guidance on cell morphology

Live cells are exquisitely sensitive to both the substratum rigidity and texture. To explore cell responses to both these types of inputs in a precisely controlled fashion, we analyzed the responses of Chinese hamster ovary (CHO) cells to nanotopographically defined substrata of different rigidities, ranging from 1.8 MPa to 1.1 GPa. Parallel arrays of nanogrooves (800-nm width, 800-nm space, and 800-nm depth) on polyurethane (PU)-based material surfaces were fabricated by UV-assisted capillary force lithography (CFL) over an area of 5 mm × 3 mm. We observed dramatic morphological responses of CHO cells, evident in their elongation and polarization along the nanogrooves direction. The cells were progressively more spread and elongated as the substratum rigidity increased, in an integrin β1 dependent manner. However, the degree of orientation was independent of substratum rigidity, suggesting that the cell shape is primarily determined by the topographical cues.     

Implementation of a piezoresistive MEMS cantilever for nanoscale force measurement in micro/nano robotic applications

The nanoscale sensing and manipulation have become a challenging issue in micro/nanorobotic applications. In particular, a feedback sensor-based manipulation is necessary for realizing an efficient and reliable handling of particles under uncertain environment in a micro/ nano scale. This paper presents a piezoresistive MEMS cantilever for nanoscale force measurement in microrobotics. A piezoresistive MEMS cantilever enables sensing of gripping and contact forces in nanonewton resolution by measuring changes in the stress-induced electrical resistances. The calibration of a piezoresistive MEMS cantilever is experimentally carried out. In addition, as part of the work on nanomanipulation with a piezoresistive MEMS cantilever, the analysis on the interaction forces between a tip and a material, and the associated manipulation strategies are investigated. Experiments and simulations show that a piezoresistive MEMS cantilever integrated into a microrobotic system can be effectively used in nanoscale force measurements and a sensor-based manipulation.     

Identification and control of a sensorized microgripper for micromanipulation

This paper presents the design and control of a sensorized microgripper using a voice coil motor and a flexure mechanism. To increase the gripping sensitivity, shape design and determination of sensor attachment position are performed using finite element analysis. Empirical models of the microgripper are acquired for the design of position control and gripping force control. By using the identified models, both the perfect tracking controller for position control and the adaptive zero-phase error tracking controller for force control are implemented. The effectiveness of the proposed model-based control methods is verified by experimental studies.     

Design and performance evaluation of a 3-DOF mobile microrobot for micromanipulation

In this paper, a compact 3-DOF mobile microrobot with sub-micron resolution is presented. It has many outstanding features: it is as small as a coin ; its precision is of sub-micrometer resolution on the plane; it has an unlimited travel range; and it has simple and compact mechanisms and structures which can be realized at low cost. With the impact actuating mechanism, this system enable both fast coarse motion and highly precise fine motion with a pulse wave input voltage controlled. The 1-DOF impact actuating mechanism is modeled by taking into consideration the friction between the piezoelectric actuator and base. This modeling technique is extended to simulate the motion of the 3-DOF mobile robot. In addition, experiments are conducted to verify that the simulations accurately represent the real system. The modeling and simulation results will be used to design the model-based controller for the target system. The developed system can be used as a robotic positioning device in the micromanipulation system that determines the position of micro-sized components or particles in a small space, or assemble them in the mesoscale structure.     

Mechanical analysis of chorion softening in prehatching stages of zebrafish embryos

During early development, the chorion envelope of the zebrafish embryo undergoes a thinning process called "chorion softening," which has so far only been characterized chemically. In this study, a micromechanical force sensing system was used to characterize and quantitate mechanical modifications of the zebrafish embryo chorion during early development. Quantitative relationships between applied forces and chorion structural deformations were established at various embryonic stages. The measured penetration force into the chorion at the blastula stage was 1.3-fold greater than those at the prehatching stage. Furthermore, chorion elastic modulus values were determined by using a biomembrane elastic model. The elastic modulus of the chorion at the blastula stage was 1.66-fold greater than that at the prehatching stage, thus indicating that the chorion envelope become mechanically "softened" at the prehatching stage. The experimental results quantitatively describe "chorion softening," which is most likely due to proteolytic activities at the prehatching stage. Gradual chorion softening during embryonic development was also artificially achieved by treating blastula chorion with pronase, a proteolytic enzyme. The forces required to penetrate the pronase-treated chorion were similar to those at the prehatching stage. This similarity suggests that "chorion softening" may be induced by the release of protease from the embryos, and the chemical nature of the process involves proteolytic fragmentation of the ZP2 protein.     

Adaptive compensation control of vehicle automatic transmissions for smooth shift transients based on intelligent supervisor

In this paper, an advanced shift controller that supervises the shift transients with adaptive compensation is presented. Modern shift control systems for vehicle automatic transmission are designed to provide smooth transients for passengers’ comfort and better component durability. In the conventional methods, lots of testing and calibration works have been done to tune gains of the controller, but it does not assure optimum shift quality at all times owing to system variations often caused by uncertainties in shifting hydraulic systems and external disturbances. In the proposed control scheme, an adaptive compensation controller with intelligent supervisor is implemented to achieve improved shift quality over the system variations. The control input pattern which generates clutch pressure commands in hydraulic actuating systems, is updated through a learning process to adjust for each subsequent shift based on continuous monitoring of shifting performance and environmental changes. The proposed algorithm is implemented and evaluated on the experimental test setup. Results from the experimental studies for several operation modes show both improved performance and adaptability of the proposed shift controller to uncertain changes of the shifting environment in vehicle power transmission systems.     

A flexible microassembly system based on hybrid manipulation scheme for manufacturing photonics components

In this paper, a flexible microassembly system based on hybrid manipulation scheme is proposed to apply to the assembly of photonics components such as lensed optical fiber ferrules and laser diode (LD) pumps. In order to achieve both high precision and dexterity in microassembly, we propose a hybrid microassembly system with sensory feedbacks of vision and force. This system consists of the distributed six degrees of freedom (DOF) micromanipulation units, the stereomicroscope, and haptic interface for the force feedback-based microassembly. A hybrid assembly method, which combines the vision-based microassembly and the scaled teleoperated microassembly with force feedback, is proposed. The feasibility of the proposed method is investigated via experimental studies for assembling micro-optoelectrical components. Experimental results show that the hybrid microassembly system is feasible for applications to the assembly of photonic components in the commercial market with better flexibility and efficiency.