用于细胞排列的介电泳微流控芯片制备与实验研究

设计并制作了一种应用于细胞排列的介电泳微流控芯片,以实现细胞的非接触、批量排列。芯片主要包括PDMS微通道和“台阶”形ITO微电极。运用仿真软件COMSOL分析了微电极所形成的电场分布,确定了最大电场强度的位置;利用MEMS加工工艺制备了ITO微电极和PDMS微通道,PDMS微通道与带有ITO电极的载玻片经过氧等离子表面处理后,对准键合获得最终的微流控芯片。通过不同频率下的介电泳实验,实现了酵母菌细胞的介电泳运动,并确定了正、负介电泳运动的电场频率。结果表明,酵母菌细胞在溶液电导率为60μS/cm的环境下,1~10 kHz时,发生负介电泳运动;0.5~10 MHz时,发生正介电泳运动;50 kHz时,没有发生介电泳运动。并在施加8 Vp-p,5 MHz交流电压信号的条件下,实现了酵母菌细胞沿“台阶”形电极边缘直线排列。     

基于ARM9的便携式电容耦合非接触电导检测器

研制了一种应用于微流控芯片的便携式电容耦合非接触电导检测器。此检测器在ARM9嵌入式平台上开发,所有功能由ARM9微处理器控制完成。检测器的硬件部分主要包括信号激励、信号调理、信号采集处理及显示单元;软件部分主要包括操作系统、驱动程序和应用程序。检测器的激励信号频率范围为0～2 MHz;电压范围为0～20 Vpp(峰峰值);检测器的外形尺寸为130 mm×102 mm×35 mm。利用此检测器测试了一种三层结构微流控芯片的检测灵敏度。该芯片由聚甲基丙烯酸甲酯电极片(包含铜检测电极)、厚度为16μm的聚二甲基硅氧烷(PDMS)绝缘层和PDMS沟道片(包含微沟道)组成。溶液在蠕动泵的驱动下,从芯片的尖端进入微沟道,并在电极处得到检测。本研究对检测器的激励频率和电压进行了优化。在优化的激励频率(50 kHz)和电压(20 Vpp)下,得到的KCl检出限为9.1μmol/L。     

阵列式对电极介电电泳芯片及其用于细胞分离富集研究

基于介电电泳原理, 设计并制作了一种新型的能够用于细胞分离和富集的微流控介电电泳芯片. 该芯片由沉积有金电极的石英基片和带有微管道的聚二甲基硅氧烷(PDMS)盖片组成. 通过在管道底部布置间距不同的对电极阵列, 增大了正介电电泳力在管道中的有效作用范围, 能够在降低施加电压的同时, 实现对流动体系中细胞样品的捕获. 在3 V和3 MHz条件下, 该DEP芯片对人血红细胞的捕获效率达到83%; 进一步通过将肝癌细胞捕获在芯片电极上可实现对红细胞和肝癌细胞混合样品的分离, 在5 V和400 kHz条件下对肝癌细胞的捕获效率达到86%.     

微流控液滴软模板制备二氧化钛中空微球

应用微流控液滴技术合成功能材料已发展成为一个新兴领域。本文以夹流结构微流控芯片产生的微液滴作为软模板,以液滴模板界面处发生的水解反应生成二氧化钛球壳,并经后续脱核处理,制备二氧化钛中空微球。采用激光诱导荧光成像、扫描电镜等手段对微球形貌结构进行了分析表征。结果表明,通过控制微流控芯片液滴合成条件,可以得到壁厚约2 μm的二氧化钛中空微球。这种以微流控液滴为模板的合成方法简单灵活,若与其他材料改性方法相结合,有望实现对更多元、更复杂功能微球材料的制备,并进一步拓宽其在光电和催化剂材料领域的应用。     

一种微型FAIMS传感器芯片的研制

基于微机电系统(MEMS)技术,研制了一种微型高场非对称波形离子迁移谱(FAIMS)传感器芯片.芯片尺寸为18.8mm×12.4mm×1.2mm,由离子化区、迁移区、离子检测区组成.采用真空紫外灯离子源在大气压环境下对样品进行离子化,经过离子化区中聚焦电极的电场作用,实现离子在进入迁移区之前的聚焦,提高离子信号的强度.通过在上下玻璃上溅射Au/Cr(300nm/30nm)金属,并与厚度为200μm、采用感应耦合等离子体(ICP)工艺刻蚀的硅片键合,形成迁移区的矩形通道,尺寸为10mm×5mm×0.2mm.离子检测区为三排直径200μm、间距100μm交错排列的圆柱阵列式微法拉第筒,能同时检测正负离子.采用频率为2MHz,最大电压为364V,占空比为30%的高场非对称方波电压进行FAIMS芯片实验.以丙酮和甲苯为实验样品,载气流速80L·h-1,补偿电压从-10V到3V以0.1V的步长进行扫描,得到了丙酮和甲苯的FAIMS谱图,验证了FAIMS芯片的性能.丙酮和甲苯的FAIMS-MS实验进一步表明FAIMS系统实现了离子分离和过滤功能.     

微流控芯片化学发光检测系统研究

在微流控芯片上实现了鲁米诺-过氧化氢-Co2+化学发光反应及分析应用研究。探讨了分离电压对电泳图谱的影响,发现在选定实验条件下,Co2+检出限可达到2.0×10-6mol/L;并且在微流控芯片上实现了Co2+与Cu2+的快速分离及检测。     

微流控二维电泳芯片的电压控制优化

基于微流控二维电泳芯片(2D-EMC)的流路特点,建立等效电阻模型,以便给出各端电压的合理取值范围,成功实现微流控芯片二维电泳分离.经实验测定各微通道电阻,在各端电压合理取值范围内,通过电流测量调整(优化)电压,得到了一组优化的电压控制方案,在化学发光-2D-EMC系统中成功实现了精氨酸和甘氨酸衍生物的二维分离.本方法显著减小了实现微流控芯片二维电泳分离的实验次数.     

微流控芯片非接触电导法测定感冒药中盐酸伪麻黄碱和氢溴酸右美沙芬

研究了用微流控芯片非接触式电导法分离检测感冒药日夜百服咛片中的两种主要成分盐酸伪麻黄碱和氢溴酸右美沙芬的方法。优化条件为:缓冲液20 mmol/L Tris 20 mmol/L H3BO3(pH=8.0);进样电压300 V;进样时间10.0 s;分离电压3.0 kV。非接触电导检测器激发电压60 V(Vp-p),频率60 kHz。两种成分的线性范围分别为20~1000 mg/L和10~1000 mg/L;检出限分别为10和5.0 mg/L;样品回收率分别为99.3%和97.6%。     

激光诱导荧光检测微流控芯片生化分析仪的研制

研制出一种集激光诱导荧光检测、微流控芯片电泳及控制系统于一体的生化分析仪。分析仪内采用可重复使用的玻璃基质微流控芯片,利用销式固定技术实现芯片的精确定位,定位精度达到±2μm。以四触点高电压系统控制芯片上的进样和电泳分离操作。激光诱导荧光检测系统采用正交光路模式,对Cy5染料的检出限达到1.0×10-10mol/L(S/N=3)。以羟乙基纤维素为筛分介质,初步进行了ΦΧ174-HaeШdigest DNAmarker限制性片段的毛细管电泳分离。     

基于离子浓差极化的立体式海水淡化微流控器件研究

海水淡化是解决人类淡水资源匮乏的一个重要途径。现有的海水淡化技术存在设备体积大、海水淡化成本高等问题。本研究采用聚二甲基硅氧烷( PDMS)制备了基于离子浓差极化原理的海水淡化器件,采用盐溶液模拟海水,进行盐离子和水分子分离的研究。研究了不同的外加电压、盐溶液在通道中的流动速度、盐溶液通道深度和Nafion纳米通道的深度等实验条件和结构参数对微流控器件分离盐离子和水分子的影响。对微流控器件的结构参数进行了优化。实验结果表明,采用外加电压为25 V、盐溶液流速为4μL/min、盐溶液通道深宽比为1：20、Nafion纳米通道深度为450~500μm的微流控器件进行盐溶液分离,除盐率可达到99%。研究结果对于开发新型高效、低能耗的海水淡化器件有重要的指导意义。     

A carbanion induced synthesis of highly congested pyrazole and imidazole containing heterocycles

An efficient approach to the synthesis of highly congested di, penta and hexacyclic pyrazoles as well as imidazole fragment containing novel heterocyclic molecule has been developed through a carbanion induced transformation of suitably functionalized 2H-pyran-2-ones, benzo[h]chromene and thiochromeno[4,3-b]pyrans. Due to the presence of fluorescence, we report their prime application metal sensor as off/on switching in ferric ions.     

α-Amino acid derived enaminones and their application in the synthesis of N-protected methyl 5-substituted-4-hydroxypyrrole-3-carboxylates and other heterocycles

A new and simple synthesis of novel N-protected methyl 5-substituted-4-hydroxypyrrole-3-carboxylates, which exist in equilibrium with their 4-oxo tautomers, has been developed in two steps starting from N-protected α-amino acids. The key intermediates are enaminones, which can also be isolated, characterized, and used for the construction of other functionalized heterocycles, before they spontaneously decompose to pyrrole products. 4-Hydroxypyrroles are prone to partial aerial oxidation but can be efficiently alkylated or reduced to stable polysubstituted pyrrolidine derivatives.     

Specific intramolecular aromatic CH insertion of diazosulfonamides

The chemoselectivity in the intramolecular CH insertion of various diazosulfonamides has been experimentally studied. The results reveal that the aliphatic 1,4-, 1,5-, or 1,6-C(sp³)?H insertions of diazosulfonamides are not accessible, while the aromatic 1,5-C(sp²)?H insertion can be realized specifically by adjusting the diazo-adjacent group. In addition, the general chemoselectivities in the intramolecular CH insertions of diazosulfonyl compounds are summarized. Generally, diazosulfones undergo both aromatic 1,5-C(sp²)?H and aliphatic 1,5- and 1,6-C(sp³)?H insertions, while diazosulfonates undergo aliphatic 1,5- and 1,6-C(sp³)?H insertions. However, diazosulfonamides only undergo aromatic 1,5-C(sp²)?H insertion.     

N-Heterocyclic carbene-palladacyclic complexes: synthesis,characterization and their applications in the C-N coupling and α-arylation of ketones using aryl chlorides

N-Heterocyclic carbene-palladacyclic complexes 3 were successfully achieved in a one-pot procedure under mild conditions. The structure of 3a was unambiguously confirmed by X-ray single crystal diffraction and it was an active catalyst in the Buchwald-Hartwig amination and α-arylation of ketones even at very low catalyst loadings (0.01?mol%).     

Selective synthesis of 4,5-dihydroimidazo- and imidazo[1,5-a]quinoxalines via modified Pictet–Spengler reaction

An efficient tandem approach for the selective synthesis of 4,5-dihydroimidazo[1,5-a]quinoxalines 6a–g and imidazo[1,5-a]quinoxalines 7a–h by the reaction of 2-imidazolyl anilines 4a–c with aryl aldehydes 5a–k under mild reaction conditions is described. Introduction of electron releasing alkyl groups in substrates 4a–b was found to be instrumental for the success of the reaction.     

Understanding the Diels-Alder reactivity of 1,2-azaborine analogues

The Diels-Alder reactivity of 1,2-heteroborines (H₄C₄B(H)X, X?=?NH, PH, AsH; O, S, Se) has been computationally explored by means of Density Functional Theory (DFT) calculations. The influence of the HB?=?X fragment on the reactivity of the system has been quantitatively analyzed in detail by means of the so-called Activation Strain Model (ASM) of reactivity. It is found that the interaction between these species and the dienophile is significantly stronger than that computed for their all-carbon isoelectronic counterpart, benzene. In addition, the strain energy plays a key role in the observed reactivity trends. The role of the aromaticity strength of these heteroarenes on the reactivity is also assessed.     

Synthesis of N-substituted carbazolones from α-iodo enaminones via Pd(0)-catalyzed intramolecular coupling under microwave irradiation

A variety of N-aryl and N-alkyl carbazolones were conveniently achieved in good to high yields via Pd₂(dba)₃-mediated intramolecular coupling of N-substituted α-iodo enaminones under microwave irradiation. The Pd(0)-catalyzed cyclization was found to proceed favorably with the more electron-deficient phenyl ring during the reactions involving unsymmetrical N,N-diaryl α-iodo enaminones. This unique property enables the construction of carbazolone skeleton containing nitro substituted benzenoid ring.     

Iodine-mediated oxidative Pictet-Spengler reaction using terminal alkyne as the 2-oxoaldehyde surrogate for the synthesis of 1-aroyl-β-carbolines and fused-nitrogen heterocycles

An efficient iodine-mediated oxidative Pictet-Spengler reaction in dimethyl sulphoxide (DMSO) using terminal alkynes as the 2-oxoaldehyde surrogate for the synthesis of aryl (9H-pyrido[3,4-b]indol-1-yl)methanones is described. The scope of the protocol includes the total synthesis of Fascaplysin, Eudistomins Y₁ and Y₂. The methodology is extended for preparing pyrrolo[1,2-a]-quinoxaline and indolo[1,5-a]quinoxaline derivatives. The utility of 1-aroyl-β-carbolines was demonstrated by performing palladium-catalyzed β-carboline directed ortho-C(sp2)-H functionalization of the phenyl ring with thiomethyl (SMe) group using DMSO as source and for accessing 4-aryl-canthin-6-ones.     

Facile synthesis of bicyclic 1-arylpyrazol-5-ones

In this Letter, we described a facile method for constructing fused bicyclic 1-arylpyrazol-5-one ring system. We employed various methylene-containing carboxylic acids as the substrates and proved that the pyrazolone ring closure requires activated methylene group in intermediate II. Accordingly, a series of structurally diversified, fused bicyclic 1-arylpyrazol-5-ones was prepared in moderate to high yields using the requisite substrates.     

Synthesis of substituted 2,4,5,6-tetrahydrocyclopenta[c]pyrazoles and 2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazoles by intramolecular nitrilimine cycloaddition

Both substituted 2,4,5,6-tetrahydrocyclopenta[c]pyrazoles and 2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazoles have been synthesized by the 3+2 intramolecular dipolar cycloaddition of nitrilimines to alkynes. This cyclization has been extended to more versatile 3-bromo derivatives by the use of alkynylbromides as dipolarophiles.