用于细胞固定的微纳SiO2基底研究

细胞阵列芯片在细胞生物学研究、药物筛选等生物医疗领域有着广阔的应用前景.针对芯片上细胞固定时需要化学修饰的限制,提出了仅通过表面结构实现细胞固定的方案.基于MEMS技术,采用DRlE在硅片上得到超疏水的微纳结构,通过简单的高温氧化工艺实现超亲水性的SiO2 结构表面;再通过控制BOE腐蚀时间得到不同形貌的基底表面.计算了基底表面上的循环肿瘤细胞的黏附效率,并在SEM下观察了细胞与基底的相互作用行为,探讨了粗糙表面影响细胞黏附的原因.实验结果表明:采用DRlE和高温氧化制备的微纳SiO2 基底表面能极大促进细胞黏附,可应用于细胞阵列芯片设计中.     

电化学阳极氧化自组织TiO2 纳米管阵列的研究

为了弄清阳极氧化制备TiO2纳米管阵列的影响因素及形成机理,研究了HF浓度W(HF)=0.1～1.0%,电压(5V～30V),时间(20min～120min)对阳极氧化TiO2纳米管阵列形貌的影响,用X射线衍射(XRD)和扫描电子显微镜(SEM)对其结构进行表征,并通过电流时间变化曲线探讨了TiO2纳米管阵列的形成机理.结果表明,氧化电压、电解液浓度、氧化时间是影响TiO2纳米管阵列形貌的主要因素,TiO2为不定形结构.只要延长时间,在低浓度W(HF)=0.1%HF溶液中也能得到TiO2纳米管阵列.阳极氧化的整个过程分为3个阶段,纳米管阵列的形成是场增强氧化、场增强氧化膜溶解和HF化学溶解共同作用并达到动态平衡的结果.     

基于BOE硅腐蚀现象的硅纳米线制作

介绍一种硅纳米线制作方法.在SOI顶层硅上制作硅纳米梁,通过离子注入形成pnp结构,利用新发现的没有特殊光照时BOE溶液腐蚀pn结n型区域现象,结合BOE溶液氧化硅腐蚀,实现硅纳米线制作.制作完全采用传统MEMS工艺,具有工艺简单,成本低,可控,可靠性好,可批量制作等优点.利用该方法制作出了厚50 nm,宽100 nm的单晶硅纳米线,制作的纳米线可用于一维纳米结构电学性能研究、谐振器研究等.     

用于光刻系统仿真的多边形处理算法

为提高光刻仿真效率,通过对光刻原理进行研究,提出了2种多边形处理算法,将掩模上的多边形图案进行切分优化,将其划分成若干矩形或三角形。在Linux环境下应用C语言设计出一个完整的光刻仿真系统,设计的具体光学参数为:光源波长为193nm,数值孔径为0.3~0.8,部分相干系数可调范围为0.2~0.8,可一次性仿真1μm×1μm到10μm×10μm范围内的45 nm~0.18μm工艺的复杂版图,并通过多次实验进行验证。实验结果表明:原版图图像的边缘细节得到保留,且该算法有效地减少了光刻模拟的计算复杂度与计算时间,整体效率提升20%以上,为当前智能传感器系统芯片的制造节省了宝贵时间。     

纳米碳化硅/硅纳米孔柱阵列湿敏性能研究

以硅纳米孔阵列(Si-NPA)为衬底,采用化学气相沉积法分别制备了SiC纳米颗粒/Si-NPA(nc-SiC/Si-NPA)和SiC纳米线/Si-NPA(nw-Si/Si-NPA)复合体系,并对其表面成分和形貌、室温湿敏性能进行了表征.实验结果表明,nc-SiC/Si-NPA和nw-SiC/Si-NPA均对水蒸气表现出...     

新型半填充微气相色谱柱芯片研究

基于微机电系统(MEMS)技术设计制造了新型半填充微气相色谱柱(μGCC)芯片,芯片的微沟道内设计有排列整齐的椭圆微柱阵列。与现有半填充μGCC相比,新型μGCC的微沟道具有更大的表面积和更均匀的流速场分布,对芯片分离度和柱效的提高起着至关重要的作用。设计的芯片成功分离了重烃类混合气体组分和苯系物,理论塔板数最高可达到9 246 plates/m。     

PDMS用加窗方式快速复制微结构

提出了一种微流控芯片中的制作方法,此方法可以复制现有芯片的任意结构,可用于实验室原有芯片的修复和整合.用窗口的方法提取结构,可排除芯片上相邻结构的干扰,得到表面光滑整齐的新芯片.特别适用于复制目前软光刻工艺尚未达到的特微结构和三维结构芯片.实验制作出的聚二甲基硅氧烷(PDMS)芯片沟道长30μm,宽5μm,深5μm,显微镜下观察芯片表面光滑,窗口内沟道性质复制良好,窗口边缘与表面之间具有明显的陡变.     

聚二甲基硅氧烷微流控芯片的制备

采用印刷电路板技术加工出芯片模具,以聚二甲基硅氧烷(PDMS)为材料制作出微流控芯片。该芯片由基片和盖片组成,微流控沟道位于基片上,深度和宽度分别为75μm和100μm,由盖片对其进行密封。考察了有绝缘漆模具和无绝缘漆模具制作的芯片的电泳分离情况。在该PDMS微流控芯片上对用异硫氰酸酯荧光素标记的氨基酸进行了电泳分离,当信噪比S/N=3时,最小检测浓度达到0.8×10-11mol/L。     

一种新颖的基于离子束刻蚀的纳米沟道制备技术

研究了一种新颖的基于MEMS工艺中离子束刻蚀的纳米沟道制备技术,通过研究离子束刻蚀微米级线条时,离子束刻蚀角度与刻蚀的轮廓形状之间的关系,在2μm线条内刻蚀出纳米沟道所需要的掩模图形,并结合KOH的各向异性腐蚀,成功获得了纳米沟道阵列.在两种不同的离子束刻蚀条件下,在2 μm图形内分别制备出单纳米沟道和双纳米沟道,最小宽度可达440 nm.     

MEMS微探针及其在嗅粘膜神经递质检测中的研究

采用微探针电极阵列对大鼠嗅粘膜神经递质进行了在体检测.基于MEMS技术,制备了具有8通道电极阵列的微探针芯片.每一电极的传感器表面为16μm×120μm或0.3 μm×120 μm尺寸.采用循环伏安法,该探针可以检测到50 nM浓度的多巴胺.将探针固定于大鼠鼻腔嗅粘膜,对多巴胺等单胺类神经递质进行了在体检测.通过二氧化碳诱导的三叉神经刺激动物模型的研究,证明微探针适合于神经递质的多位点实时测量.     

大功率白光LED驱动电路的双环检测方法

基于CSMC0.5μm标准CMOS工艺,设计了一种带有双环检测的大功率LED恒流驱动芯片。仿真结果表明,芯片可在2MHz频率下工作,驱动电流最高可达1.5A,在24V电源电压时,电源效率可达95%。当电源电压在6V跳变±10%,驱动1W350mA的LED时,LED电流精度达0.02%。对比单环检测模式,该电路的LED驱动电流响应时间缩短了近2/3。此模式在保持高精度恒流和高效率的同时,有效地缩短了LED驱动电流的响应时间。     

A microfluidic chip of multiple-channel array with various oxygen tensions for drug screening

Oxygen participates in numbers of cellular activities and behaviors in both normal and pathological tissues. In physiological microenvironment, oxygen tension is generally below 21 % and varies in different species, states and regions of organs. However, present studies of cellular behavior in vitro are performed in an ambient level, which is not conformity to the reality in vivo. In this study, a microfluidic device was developed to generate controllable oxygen tensions on a multiple-channel array chip for high-throughput drug screening. Controlling various concentrations of chemical reagents with confined flow rate, specific oxygen tensions can be established from 1.6 to 21 %, where the oxygen tension of each channel can be modulated in demand. When the concentrations of pyrogallol change from 100 to 700 μg/mL with the flow rate of 5 μL/min, oxygen tensions in cell chambers range from 12.5 to 3.87 %. Pyrogallol with the concentration of 0 μg/mL is used as the control group to obtain 20.9 % oxygen condition. The developed microfluidic chip was used to investigate the cytotoxicity of TPZ and cisplatin, and the results demonstrate different manners of two oxygen-sensitive anti-tumor drugs in oxygen-dependent cytotoxic responses. Due to its character, the microfluidic device is believed to establish any desired and measurable oxygen tension distribution for pharmacology development, which is promising to improve efficiency and reduce tedious operation for pharmaceutical studies.     

A superposable double-gradient droplet array chip for preparation of PEGDA microspheres containing concentration-gradient drugs

This article describes a superposable double-concentration-gradient droplet array chip, which allows a variety of concentration combinations of two components to be formed simultaneously. The concentration gradients generated from two layers of the chip could be arbitrarily superimposed by adjusting the center angle between the two bonding layers. With the aqueous phase flow rate of 1.0 μL min^?1 and the oil phase flow rate of 30.0 μL min^?1, the droplets about 58 μm in diameter were produced, and the coefficients of variation were below 6.0% for single channel and 5.7% for all the channels. Using a dual-32-channel superposable gradient droplet array chip, poly(ethylene glycol) diacrylate (PEGDA) microspheres containing concentration-gradient combinations of rhodamine B and fluorescein were fabricated to demonstrate the capability of PEGDA for encapsulating hydrophilic and hydrophobic substances, as well as the proper concentration-gradient distribution. Furthermore, PEGDA microspheres loaded with two anticancer drugs, hydrophilic doxorubicin hydrochloride and hydrophobic paclitaxel, of 17 concentration combinations were simultaneously prepared. The drug-induced apoptosis of human uterine cervix cancer cells was investigated using the dual-drug-loaded PEGDA microspheres. The optimum synergistic concentration combination of the two drugs was 12.5 μg mL^?1 for doxorubicin hydrochloride and 43.75 μg mL^?1 for paclitaxel according to the preliminary screening. The superposable double-gradient droplet array generator was demonstrated to be a promising platform for screening multiple drug combination in microcarriers.     

用于细胞外电信号测量的CMOS集成生物 传感芯片的研究

新型的细胞外电信号传感芯片是采用0.6 μm标准CMOS工艺设计制造,片上集成了6×6单元有源传感阵列、模拟多路选择器、输出缓冲器、参考源和数字控制电路.有源传感单元面积为60μm×60μm,包含15μm×15μm的传感电极和预处理电路,能够线性放大幅值范围100μV～25 mV的微小信号,电压增益为40dB.并采用相关二次采样工作模式降低固定模式噪声,提高传感器的精度.在标准CMOS工艺基础上,应用无电浸镀金改进传感电极的生物兼容性,并采用特殊封装技术提高芯片在溶液环境中的稳定性.溶液中模拟生物信号测量验证了该芯片的功能.     

Isolation and elution of Hep3B circulating tumor cells using a dual-functional herringbone chip

Circulating tumor cells (CTCs), which are derived from primary tumor and circulate to secondary site, are regarded as the cause of metastasis. Many methods have been applied for CTC isolation and enumeration so far. However, it remains a challenge to effectively elute the captured cells from the device for further cellular and biomolecular analyses. In this paper, we fabricate a dual-functional herringbone chip to achieve both CTC capture and elution based on the immunoassay of epithelial cell adhesion molecule antigen expressed on the surface of human liver cancer cell line Hep3B. The results show that the capture limit of Hep3B cells can reach as low as 3 cells per ml with capture efficiency over 50 % on average. On the other hand, the elution rate of more than 50 % of the captured Hep3B cells can be achieved for cell density ranging from 5 to 2 × 10³/ml. It demonstrates that this herringbone chip exhibits excellent dual functions with high capture efficiency and considerable elution rate, indicating its promising capability for clinical assay in cancer diagnosis.     

一个超高速FFT阵列式计算结构设计方案

本文分析了ＣＯＲＤＩＣ算法和ＦＦＴ算法的在内在联系，设计了基于ＣＯＲＤＩＣ算法的四个蝶形运算器芯片，并在此基础上构成了ＦＦＴ阵列式计算结构，Ｎ＝２＾ｍ点的ＦＦＴ计算速度可达到微秒级，有很好的性能人格比，在超高速实时信号处理中有广阔的应用前景。     

Microfluidic chips for cells capture using 3-D hydrodynamic structure array

Microfluidic chips were designed and fabricated to capture cells in a relative small volume to generate the desired concentration needed for analysis. The microfluidic chips comprise three-dimensional (3-D) cell capture structures array fabricated in PDMS. The capture structure includes two layers. The first layer consists of spacers to create small gap between the upper layer and glass. The second layer is a sharp corner U-shaped compartment with sharp corners at the fore-end. And another type capture structure with Y-shaped fluidic guide has been designed. It was demonstrated that the structures can capture cells in theory, using Darcy–Weisbach equation and COMSOL Multiphysics. Then yeast cell was chosen to test the performance of the chips. The chip without fluid guides captured ~1.44 × 10⁵ cells and the capture efficiency was up to 71 %. And the chip with fluid guides captured ~5.0 × 10⁴ cells and the capture efficiency was ~25 %. The chip without fluid guides can capture more cells because the yeast cells in the chip without fluid guides are subject to larger hydrodynamic drag force.     

Vertical Si nanowire with ultra-high-aspect-ratio by combined top-down processing technique

Vertical Si nanowires with ultra-high-aspect-ratio were fabricated using a combined process of deep reactive ion etching and sacrificial oxidation. The combined process starts with etching the Si substrates by the Bosch process to form micrometer-scale structures. The etched micrometer-scale structures are shrunk to nanometer-scale by sacrificial oxidation. The fabricated Si nanowires that were aligned vertically to the substrate had a diameter of less than 200 nm and a length greater than 10 μm. One of the fabricated Si nanowires had a diameter of 110 nm and a length of 11 μm. The resulting aspect-ratio reached 100, which is a value that is significantly high for vertical Si nanowires fabricated by using a top-down approach.     

3D amoeboid migration of a eukaryotic cell in a fiber matrix

A basic event in amoeboid-type cell movement (ATCM) is extension of an exploratory cell protrusion called a pseudopod. ATCM of cells among the fibrous macromolecules of the extracellular matrix (ECM) is crucial to tissue development and wound healing, and a key process in immune response and cancer invasion. We studied ATCM by developing a computational model of pseudopod extension/retraction driving ECM sensing, cell-matrix adhesion, and cell translocation within the 3D ECM mesh. We were successful in producing a biomorphic ATCM motion cycle involving viscoelastic protrusion and attachment to ECM, cell body displacement, and cell detachment from old adhesion sites. The simulated trajectories were in general persistent random walks resembling ATCM patterns reported for patrolling immune cells and cancer cell invasion.