Yi-Ping Ho

A robust and reliable stress-induced self-assembly mechanism for optical devices

Based on the MUMPs platform, this study has established an improved surface micromachining process (MUMPs-like process) to improve the reliability of the stress-induced beams. A novel rigid supporting mechanism is devised to prevent the mirror from offset. Furthermore, with this mechanism various pop-up mirrors could be accomplished. According to this MUMPs-like process, devices are fabricated to evaluate the performance of this assembly mechanism.

Microfluidics-mediated isothermal detection of enzyme activity at the single molecule level

Conventional analysis of enzymatic activity, often carried out on pools of cells, is blind to heterogeneity in the population. Here, we combine microfluidics with a previously developed isothermal rolling circle amplification-based assay to investigate multiple enzymatic activities in down to single cells. This microfluidics-meditated assay performs at very high sensitivity in picoliter incubators with small quantities of biological materials. Furthermore, we demonstrate the assays capability of multiplexed detection of at least three enzyme activities at the single molecule level.

Quantitative kinetic analysis of DNA nanocomplex self-assembly with Quantum Dots FRET in a microfluidic device

The demand for safer and more efficient non-viral gene vectors has increased with the recent progress of genetic medicine. Appropriate nanocomplex assembly of DNA and gene carriers is critical for successful cellular entry and transfection. However, there is a lack of knowledge on this self-assembly process, let alone the controllability of monodisperse nanocomplexes. This paper describes a novel platform integrating nanobiophotonics (quantum dots-mediated FRET) and microfluidic technology to determine binding kinetics that govern the structural and chemical properties of DNA nanocomplexes. We anticipate that this method will elucidate mechanistic and kinetic insights into the self-assembly process of nanocomplexes which may facilitate the rational design of more efficient gene carriers. In addition, a microfluidic platform offers many advantages, including small volume, fast response to external stimulations, continuous monitoring and real-time control of reaction environments, which may be potentially used to generate more monodisperse complexes.

A Novel MUMPs-compatible single-layer out-of-plane electrothermal actuator

Microactuator is one of the key components for the microelectromechanical systems (MEMS), and it can be categorized as out-of-plane and in-plane according to the motion types. Most of the existing out-of-plane thermal actuators are multi-layer structures. In this paper, a novel electrothermal single-layer out-of-plane actuator is provided and it characteristics and advantages of this device are stated as follows: (1) This actuator is consisted of only a single thin film material, therefore, it can prevent from delaminating after a long-term operation. Besides, owing to its symmetric geometric design, the inner-beams of this structure don’t have any current passed through them and the inner-beams also provide a geometric constraint to allow the two free ends of the structure to bend upwards symmetrically. (2) This device can be operated at a relative low voltage (<5 volt), and deflected upwards about 4 μm in the experiment test. Besides, the fabrication process is very simple and it is MUMPs(Multi-User MEMS Processes)-compatible. Presently, a prototype structure has been successfully fabricated and tested. This structure offers the potential applications in the adaptive optics systems, and Fabry-Perot filters, etc. Besides, it also provides an interface to cooperate with integrated circuits (IC) and various optical elements to construct an embedded-control optical system.

Extraction of active enzymes from “hard-to-break-cells”: Evaluation by a RCA-based assay

We present the utilization of a rolling circle amplification (RCA) based assay to investigate the extraction efficiency of active enzymes from a class of “hard-to-break” cells, yeast Saccaramyces cerevisiae. Current analyses of microorganisms, such as pathogenic bacteria, parasites or particular life stages of microorganisms (e.g. spores from bacteria or fungi) is hampered by the lack of efficient lysis protocols that preserve the activity and integrity of the cellular content. Presented herein is a flexible scheme to screen lysis protocols for active enzyme extraction. We also report a gentle yet effective approach for extraction of active enzymes by entrapping cells in microdroplets. Combined effort of optimized extraction protocols and effective analytical approaches is expected to generate impact in future disease diagnosis and environmental safety.

Single cell enzyme diagnosis on the chip

Conventional diagnosis based on ensemble measurements often overlooks the variation among cells. Here, we present a droplet-microfluidics based platform to investigate single cell activities. Adopting a previously developed isothermal rolling circle amplification-based assay, we demonstrate detection of enzymatic activities down to the single cell level with small quantities of biological samples, which outcompetes existing techniques. Such a system, capable of resolving single cell activities, will ultimately have clinical applications in diagnosis, prediction of drug response and treatment evaluation, as well as fundamental impact on the understanding of disease mechanisms.

Unexpected properties of polymeric DNA-nanocomplexes synthesized in picoliter droplets

Nucleic acids have emerged as a promising class of drugs but require a safe and efficient delivery system to realize their full therapeutic potential. While non-viral vectors may be safer than viral vectors, the need to improve their delivery efficiencies has provided the impetus to control the structural and chemical properties of DNA nanocomplexes. We have previously shown uniform size distribution of gene-loaded nanocomplexes synthesized in picoliter droplets. This study demonstrated that these homogeneous nanocomplexes reduced cytotoxicity significantly while the therapeutic efficacy was not compromised, which will help pave the way of applying gene as a “drug”.

Multiplexed Detection of Anthrax Sequences with Quantum Dot Nanoprobes

We demonstrate a bio-agent detection scheme using colocalization of target-selective quantum dot nanoprobes. The presence of a target is shown through the colocalized emissions of bound events and easily distinguished with colorimetric measurements, negating an additional step for separation of unbound probes. Multiplexed detection can be achieved by multiple quantum dots with spectrally separable emissions. Genetic analysis of anthrax pathogenicity-relevant sequences serves as a multiplexed example of this approach. Furthermore, this method shares characteristics with a homogeneous format which leads to better reaction kinetics and faster detection compared with conventional solid-phase approaches.

Design of an acoustic wave actuator using Lorentz force

In this study, we developed a torsional micromachined receiver array to generate acoustic wave based on Lorentz force. The receiver array is constructed by many micro mirror components with which two pair of leads were laid around each mirror edge. In each component, a direct and an alternating driving signal were applied to each pair of leads, respectively. The mirror components will then rotate to an angle and oscillate upon the application of a specific magnetic field induced by Lorentz force. The alternating signal drives the mirror to oscillate and to generate acoustic waves of the same frequency as the alternating signal. The strength of the alternating signal and the amount of the mirror components determine the power density of the acoustic waves. The direct signal is applied on one of the paired leads that transacts with the magnetic field. Lorentz force then rotates the mirror component to a torsional angle that is proportional to the direct signal strength. Therefore, under a specific static magnetic field, driving the mirrors with different direct signal may focus the acoustic waves. With the focusing mechanism, the acoustic wave is capable of scanning in various depths, which could be reached by continuously changing the direct signal strengths. Additionally, applying the direct signals based on appropriate timing will produce strong wave by reconstructed interference, and the acoustic waves will be focused effectively. The acoustic waves then have much higher resolution and can be utilized similar to light waves.