Qiao Lin

MEMS flow sensors for nano-fluidic applications

This paper presents micromachined thermal sensors for measuring liquid flow rates in the nanoliter-per-minute range. The sensors use a boron-doped polysilicon thin-film heater that is embedded in the silicon nitride wall of a microchannel. The boron doping is chosen to increase the heaters temperature coefficient of resistance within tolerable noise limits. And the microchannel is suspended from the substrate to improve thermal isolation. The sensors have demonstrated a flow rate resolution below 10 nL/min, as well as the capability for detecting micro bubbles in the liquid. Heat transfer simulation has also been performed to explain the sensor operation and yielded good agreement with experimental data.

A Parylene micro check valve

This paper presents a micro check valve that features a bulk-micromachined valve seat (with an orifice) and a new twist-up tethered Parylene-membrane. The twist-up tethers allow large membrane displacement, and thereby reduce membrane-induced flow resistance to a negligible level. Testing results confirm the excellent performance of our valves. For example, the valves have low cracking pressures (less than 0.5 kPa for nitrogen), high reverse pressure (seater than 600 kPa) and low reverse leakage (undetectable with a 0.2 ml/min flow meter resolution). Fluid flow models and analysis of the performance characteristics of the micro valves are presented.

Surface-enhanced Raman spectroscopy based quantitative bioassay on aptamer-functionalized nanopillars using large-area Raman mapping.

Surface-enhanced Raman spectroscopy (SERS) has been used in a variety of biological applications due to its high sensitivity and specificity. Here, we report a SERS-based biosensing approach for quantitative detection of biomolecules. A SERS substrate bearing gold-decorated silicon nanopillars is functionalized with aptamers for sensitive and specific detection of target molecules. In this study, TAMRA-labeled vasopressin molecules in the picomolar regime (1 pM to 1 nM) are specifically captured by aptamers on the nanostructured SERS substrate and monitored by using an automated SERS signal mapping technique. From the experimental results, we show concentration-dependent SERS responses in the picomolar range by integrating SERS signal intensities over a scanning area. It is also noted that our signal mapping approach significantly improves statistical reproducibility and accounts for spot-to-spot variation in conventional SERS quantification. Furthermore, we have developed an analytical model capable of predicting experimental intensity distributions on the substrates for reliable quantification of biomolecules. Lastly, we have calculated the minimum needed area of Raman mapping for efficient and reliable analysis of each measurement. Combining our SERS mapping analysis with an aptamer-functionalized nanopillar substrate is found to be extremely efficient for detection of low-abundance biomolecules.

Simulation studies on nonlinear dynamics and chaos in a MEMS cantilever control system

We discovered period doubling and chaos in a simulated MEMS cantilever system with electrostatic sensing and actuation, intended for a MEMS based mass storage chip, with and without servo control. We used a graphical interface for a Poincare map method that allowed us to simulate multiple initial conditions simultaneously. We investigated both the static and dynamic instabilities of the MEMS cantilever system subjected to weak and strong disturbances. We observed bistability and a Hopf bifurcation in the closed loop controlled cantilever system without disturbances. We simulated the loop gain and the phase margin when the system was subjected to weak disturbances. Furthermore, we have found the period doubling, chaos and strange attractors for both the open and closed loop cantilever systems subjected to strong disturbances. For one case the stable operation range is significantly reduced by 25% because of a chaotic response.

Development of boronic acid grafted random copolymer sensing fluid for continuous glucose monitoring

We have previously presented a microelectromechanical system (MEMS) based viscometric sensor for continuous glucose monitoring using protein Concanavalin A (Con A). To address its drawbacks, including immunotoxicity and instability issues, we have synthesized stable, biocompatible copolymers poly(acrylamide-ran-3-acrylamidophenylboronic acid) (PAA-ran-PAAPBA) for viscosity based glucose sensing. We found that PAA-ran-PAAPBA showed very high binding specificity to glucose. Several key factors such as polymer compositions, polymer molecular weights and polymer concentrations have been investigated to optimize viscometric responses. This polymer is able to detect glucose under physiological pH conditions in a reversible manner. Therefore, it has the potential to enable a highly reliable, continuous monitoring of glucose in subcutaneous tissue using the MEMS device.

A stiffness-based quality measure for compliant grasps and fixtures

This paper presents a systematic approach to quantifying the effectiveness of compliant grasps and fixtures of an object. The approach is physically motivated and applies to the grasping of two- and three-dimensional objects by any number of fingers. The approach is based on a characterization of the frame-invariant features of a grasp or fixture stiffness matrix. In particular, we define a set of frame-invariant characteristic stiffness parameters, and provide physical and geometric interpretation for these parameters. Using a physically meaningful scheme to make the rotational and translational stiffness parameters comparable, we define a frame-invariant quality measure, which we call the stiffness quality measure. An example of a frictional grasp illustrates the effectiveness of the quality measure. We then consider the optimal grasping of frictionless polygonal objects by three and four fingers. Such frictionless grasps are useful in high-load fixturing applications, and their relative simplicity allows an efficient computation of the globally optimal finger arrangement. We compute the optimal finger arrangement in several examples, and use these examples to discuss properties that characterize the stiffness quality measure.

A MEMS Thermal Biosensor for Metabolic Monitoring Applications

This paper presents a microelectromechanical systems (MEMS) differential thermal biosensor integrated with microfluidics for metabolite measurements in either flow-injection or flow-through mode. The MEMS device consists of two identical freestanding polymer diaphragms, resistive heaters, and a thermopile between the diaphragms. Integrated with polymer-based microfluidic measurement chambers, the device allows sensitive measurement of small volumes of liquid samples. Enzymes specific to a metabolic analyte system are immobilized on microbeads packed in the chambers. When a sample solution containing the analyte is introduced to the device, the heat released from the enzymatic reactions of the analyte is detected by the thermopile. The device has been tested with glucose solutions at physiologically relevant concentrations. In flow-injection mode, the device demonstrates a sensitivity of approximately 2.1 muV/mM and a resolution of about 0.025 mM. In flow-through mode with a perfusion flow rate of 0.5 mL/h, the sensitivity and resolution of the device are determined to be approximately 0.24 muV/mM and 0.4 mM, respectively. These results illustrate that the device, when integrated with subcutaneous sampling methods, can potentially allow for continuous monitoring of glucose and other metabolites.

A MEMS viscometric sensor for continuous glucose monitoring

We present a MEMS sensor aiming to enable continuous monitoring of glucose levels in diabetes patients. The device features a magnetically-driven vibrating microcantilever, which is situated in a microchamber and separated from the environment by a semi-permeable membrane. Glucose sensing is based on affinity binding principles using a solution of dextran concanavalin-A (Con A) as the sensing fluid. The glucose concentration is determined by detecting viscosity changes induced by the binding of glucose to Con A through the measurement of the cantilevers vibration parameters. The device is capable of measuring physiologically relevant glucose concentrations from 0 to 25 mM with a resolution better than 0.025 mM and a phase sensitivity better than 0.4° mM−1. The response of the sensor to glucose concentration changes has a time constant down to 4.27 min, and can be further improved with optimized device designs.

Experiments and simulations of MEMS thermal sensors for wall shear-stress measurements in aerodynamic control applications

MEMS thermal shear-stress sensors exploit heat-transfer effects to measure the shear stress exerted by an air flow on its solid boundary, and have promising applications in aerodynamic control. Classical theory for conventional, macroscale thermal shear-stress sensors states that the rate of heat removed by the flow from the sensor is proportional to the 1/3-power of the shear stress. However, we have observed that this theory is inconsistent with experimental data from MEMS sensors. This paper seeks to develop an understanding of MEMS thermal shear-stress sensors through a study including both experimental and theoretical investigations. We first obtain experimental data that confirm the inadequacy of the classical theory by wind-tunnel testing of prototype MEMS shear-stress sensors with different dimensions and materials. A theoretical analysis is performed to identify that this inadequacy is due to the lack of a thin thermal boundary layer in the fluid flow at the sensor surface, and then a two-dimensional MEMS shear-stress sensor theory is presented. This theory incorporates important heat-transfer effects that are ignored by the classical theory, and consistently explains the experimental data obtained from prototype MEMS sensors. Moreover, the prototype MEMS sensors are studied with three-dimensional simulations, yielding results that quantitatively agree with experimental data. This work demonstrates that classical assumptions made for conventional thermal devices should be carefully examined for miniature MEMS devices.

Specific capture and temperature-mediated release of cells in an aptamer-based microfluidic device

Isolation of cells from heterogeneous mixtures is critically important in both basic cell biology studies and clinical diagnostics. Cell isolation can be realized based on physical properties such as size, density and electrical properties. Alternatively, affinity binding of target cells by surface-immobilized ligands, such as antibodies, can be used to achieve specific cell isolation. Microfluidics technology has recently been used in conjunction with antibody-based affinity isolation methods to capture, purify and isolate cells with higher yield rates, better efficiencies and lower costs. However, a method that allows easy release and collection of live cells from affinity surfaces for subsequent analysis and detection has yet to be developed. This paper presents a microfluidic device that not only achieves specific affinity capture and enrichment, but also enables non-destructive, temperature-mediated release and retrieval of cells. Specific cell capture is achieved using surface-immobilized aptamers in a microchamber. Release of the captured cells is realized by a moderate temperature change, effected via integrated heaters and a temperature sensor, to reversibly disrupt the cell-aptamer interaction. Experimental results with CCRF-CEM cells have demonstrated that the device is capable of specific capture and temperature-mediated release of cells, that the released cells remain viable and that the aptamer-functionalized surface is regenerable.