Ming-Yu Lin

Automatic segmentation of abnormal cell nuclei from microscopic image analysis for cervical cancer screening

In this paper, two methods of microscopic image analysis were presented to classify the abnormal cells in Papanicolaou(Pap) smear for cervical cancer screening. Our goal is to extract those cell nuclei which are abnormally large size, bizarre shape as well as hyper density and we hope to apply this method to the different kinds of abnormal cells. The global information of the image and the local image condition were meantime considered. The reported method searched whole picture by scanning on different axes and determined the locations of abnormal cell nuclei with high contrast This developed method is also able to find cell nuclei, those were almost as bright as the background. Using the reported cytological image analysis, we successfully recognized the abnormal cells such as squamous intraepithelial neoplasia (SIL) and differentiated them from the normal epithelial cells.

Ultrahigh-sensitivity CdS photoconductors with instant response and ultralow power consumption for detection in low-light environments

In this study we describe a low-cost cadmium sulfide (CdS) photoconductor that behaves as a highly sensitive and rapidly responding detector toward low-intensity light. Through the observation of TEM images and analysis of micro-Raman spectra, the degree of crystallization of CdS films increased and their dislocation defects were removed effectively after treatment with several shots from a KrF excimer laser. Such laser treatment of CdS photoconductors could be conducted in air and completed within a few seconds. At a very low bias voltage of 1 mV, the laser-treated CdS device provided a record high responsivity of 7200 A W−1 and a detectivity of 1015 Jones. In addition, at a normal bias voltage of 1 V, it displayed an extremely high responsivity of 7 × 106 A W−1 and a detectivity of 6 × 1016 Jones. The measured response time of the laser-annealed CdS device from the dark to illumination at 10−2 fW μm−2 was only 40 ms—much faster than the shutter speed or exposure time required for a professional digital camera for such low-light image detection. Accordingly, KrF laser annealing is a simple and rapid process that can significantly enhance the low-light detection properties of CdS, a commercial photoconductor. Our strategy proposed herein appears to hold great potential for ultralow-light image detection with ultralow power consumption.

Guidance of neural regeneration on the biomimetic nanostructured matrix

Biomimetic materials are used for creating microsystems to control cell growth spatially and elicit specific cellular responses by combining complex biomolecules with nanostructured surfaces. Intercellular cell-to-cell and cell-to-extracellular matrix (ECM) interactions in biomimetic materials have demonstrated potential in the development of drug discovery platforms and regeneration medicine. In this study, we developed a biomimetic nanostructured matrix by using various ECM molecular layers to create a biomimetic and biocompatible environment for realizing neuronal guidance in neural regeneration medicine. Silicon-based substrates possessing nanostructures were modified using different ECM proteins and peptides to develop a biomimetic and biocompatible environment for studying neural behaviors in adhesion, proliferation, and differentiation. The substrates were flat glass, flat silicon wafers (FWs), and nanorod-structured wafers prepared using wet etching. The three substrates were then functionalized using laminin-1 peptide, PA22-2-contained active isoleucine-lysine-valine-alanine-valine (IKVAV) peptide, and poly-d-lysine (PDL), separately. When PC12 cells were cultured and differentiated on the modified substrates, the cells were able to elongate the neurites on the glass and FW, which was coated with three types of peptide. More differentiated neurons were observed on the nanorod-structured wafers coated with laminin than on those coated with IKVAV or PDL. For achieving directional guidance of neurite outgrowth, substrates exhibiting a grating pattern of nanorods were partially collapsed by the pulling force of water, leaving few nanorods, which support the net form of laminin on the surface. Furthermore, we fabricated the topological nanostructure-patterned wafer coated with laminin and successfully manipulated the extension and direction of neurites by using more than 80 μm of a single soma. This approach demonstrates potential as a facile and efficient method for guiding the direction of single axons and for enhancing neurite outgrowth in studies on nerve regenerative medicine.

Functionalization, re-functionalization and rejuvenation of ssDNA nanotemplates

Single-stranded DNA (ssDNA) with repetitive sequence was demonstrated to be a versatile nanotemplate for introducing biological activity in a self-assembled manner. Re-functionalization and rejuvenation of the ssDNA nanotemplate were achieved under mild biological conditions without using high temperature and strong alkaline treatment to denature DNA.

CMOS phototransistor device : A total solution for skin whitening assays

Three skin whitening assays combining the semiconductor technology was demonstrated for screening the drug candidate and discussing the mechanisms of melanogenesis in medical cosmetics. We proposed a miniaturized photometric system using complementary metal oxide semiconductor (CMOS) phototransistor as a detector with high sensitivity. The CMOS phototransistor was a small, portable optoelectronic device with enlarged depletion region of the outer Nwell/Pwell ring-shaped photodiode, able to cause a sensitive shift of the threshold voltage and enhance photocurrent response. The device was further connected to IC system to show it ability for high-throughput screening needed in the pharmaceutical industry. Three methods for evaluating effects of skin whitening agent were applied, including 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, melanin amount measurement, and tyrosinase assays. The change of light absorbance due to enzymeatic catalysis was easily measured with the proposed system. The skin whitening effects by kojic acid was determined and comparable to the commercial system.

Direct detection of long, periodic, ssDNA nanostructures assembled on CMOS transistor arrays

DNA is a wonderful material for the construction of nanostructures for a variety of applications. This paper describes a novel platform integrating single-stranded DNA (ssDNA) nanotemplates with CMOS-compatible, field-effect sensors. The field-effect sensor was based on oxide-semiconductor field-effect transistors (OSFETs), which were monolithically-integrated with signal-processing circuits to enhance the signal-to-noise ratio, and to detect the construction of ssDNA nanotemplate from complex DNA-protein interactions. The ssDNA nanotemplate on the transistor arrays was prepared by isothermal rolling circle amplification (RCA) through DNA aptamer-protein recognition and self-assembly strategy. The growth of the DNA nanostructure was monitored in situ, real-time and label-free on OSFET.

DNA nanotemplates as an innovative material for optic application

Messages encoded from DNA sequence provide extensional structural and functional information in constructing DNA nanostructures. Therefore, DNA is used more than just as a genetic blueprint of life, it is also as innovative building blocks for building up various innovative nanomaterials with nano-meter resolution and micro-meter scale length. Long, and single-stranded DNA with repetitive sequence was in situ synthesized on silicon-based substrate and served as a nanotemplate to incorporate variable heteroelements, including enzymes, nanoparticles. Optical properties of gold nanoparticle chains were measured and extended applications of DNA nanotemplates in optics and nanotechnology.

A miniature CMOS optoelectronic biosensor for screening skin-whitening agents

A miniature CMOS optoelectronic biosensor is proposed for screening whitening agents. Based on the principle of absorption photometry, this biosensor is mainly composed of a green LED, a CMOS phototransistor, and a slide for performing the biochemical reactions. The requirement of the sample volume is only 10 µl, much less than those in commercial instruments. Melanin assay and MTT assay were performed to evaluate the whitening mechanisms. Experimental results demonstrated that the density of 5×104 cells/ml can be successfully detected for both assays. This portable biosensor has great potential toward personalized diagnostic kits for further applications.

Building the long, periodic ssDNA nanotemplate from tumor marker recognition for nanodevice

The programmable self-assembly of molecular nanostructures plays a crucial role in the development of nanodevices for molecule recognition. A self-assembly, periodic ssDNA nanotemplate based on aptameric recognition of tumor marker, PDGF was in situ constructed on the silicon-based substrate. The long, periodic ssDNA nanotemplate was further elongated up to 454 nm through rolling circle amplification at room temperature. The process of self-growing DNA nanotemplate based on aptameric recognition was directly visualized through nanoprobing technology.