Complementary metal oxide semiconductor compatible fabrication and characterization of parylene-C covered nanofluidic channels with integrated nanoelectrodes     

Chih-kuan Tung  Robert Riehn    Robert H. Austin 《Biomicrofluidics》2009,3(3)

Nanochannels offer a way to align and analyze long biopolymer molecules such as DNA with high precision at potentially single basepair resolution, especially if a means to detect biomolecules in nanochannels electronically can be developed. Integration of nanochannels with electronics will require the development of nanochannel fabrication procedures that will not damage sensitive electronics previously constructed on the device. We present here a near-room-temperature fabrication technology involving parylene-C conformal deposition that is compatible with complementary metal oxide semiconductor electronic devices and present an analysis of the initial impedance measurements of conformally parylene-C coated nanochannels with integrated gold nanoelectrodes.No two cells are exactly alike, either in terms of their genome, the genomic epigenetic modification of the genome, or the expressed proteome.¹ The genomic heterogeneity of cells is particularly important from an evolutionary perspective since it represents the stages of evolution of a population of cells under stress.² Because of the important variances in the genome that occur from cell to cell, it is critical to develop genomic analysis technologies which can do single-cell and single molecule genomic analysis as an electronic “direct read” without intervening amplification steps.^{3, 4, 5, 6, 7, 8} In this paper, we present a technique which uses conformal coverage of nanochannels containing nanoelectrodes using a room-temperature deposition of parylene-C, a pin-hole-free, excellent electrical insulator with low autofluorescence.⁹ This procedure should open the door to integration of many kinds of surface electronics with nanochannels. One of the most difficult aspects in introducing electronics into nanochannel technology is the sealing of nanochannel so that the electrodes are not compromised by harsh chemicals or high temperatures. There are various methods to form nanochannels containing nanoelectrodes, including wafer bonding techniques,¹⁰ removal of sacrificial materials,¹¹ and nonuniform sputtering deposition.¹² Methods employing a sacrificial layer removal show the greater compatibility to electronic integration, but current methods to remove sacrificial materials require either high temperatures¹¹ or harsh chemicals.^{13, 14}The basic device consisted of 12 mm long, 100 nm wide, 100 nm high nanochannels interrogated by 22 pairs of 30 nm wide gold nanoelectrodes. The outline of the fabrication process is shown in Fig. ​Fig.1.1. The fabrication process was carried out on a standard 4 in. single-side polished p-type ⟨100⟩ silicon wafer with 100 nm of dry thermal oxide on the top as an insulating layer, which also helped the wetting of the nanochannels. The first step involved nanofabrication of the 25 nm thick nanoelectrodes on the SiO₂ top of the wafer using electron beam lithography (EBL). External gold connection pads were constructed using standard metal lift-off techniques and photolithography to connect to the nanoelectrodes. A Raith E-Line e-beam writing system (Raith USA, Ronkonkoma, NY) was used to expose polymethyl methacrylate (PMMA) for metal lift-off. Figure ​Figure1a1a shows a scanning electron microscopy (SEM) image of the nanoelectrodes. The 100 nm sealed nanochannels were constructed using sacrificial removal techniques. We used EBL to expose a 100 nm thick film of PMMA over the gold nanolines in the region around the nanolines, leaving behind lines of unexposed sacrificial layer of PMMA. We next evaporated 25 nm of SiO₂ over the nanolines to improve the surface wetting properties of nanochannel and then conformally coated with 4 μm thick of parylene-C [poly(chloro-p-xylylene)] using a Specialty Coating Systems model PDS 2010 parylene coating system (SCS Systems, Indianapolis, IN). Access holes for the gold electrodes and the feeding channels were etched through by oxygen plasma and 1:10 buffered oxide etchant. To avoid autofluorescence induced in parylene by an active plasma¹⁵ and ambient UV radiation,¹⁶ it is important not to expose the remaining parylene with plasma and to keep the samples in the dark. The sacrificial removal of PMMA in the nanochannels was done in four steps: (1) soaking the chip in 55 °C 1165 MicroChem resist remover (MicroChem, Newton, MA) for 36 h, (2) room-temperature soaking in 1,2-dichloroethane for 12 h, (3) soaking in room-temperature acetone for 12 h, and (4) drying the nanochannels by critical point drying (CPD-030, BAL-TEC AG, Principality of Liechtenstein), which served to prevent the collapse of the nanochannel resulting from surface tension of the acetone.Open in a separate windowFigure 1(a) SEM image of gold nanoelectrodes; scale bar is 200 nm. (b) 100×100 nm² PMMA nanoline is written over the gold nanoelectrodes by exposure of the surrounding PMMA. (c) Parylene-C conformal coating over the PMMA nanoline. PMMA is dissolved and parylene-C etched by reactive ion etching.Conductance measurements were done using ac techniques. The ac impedance Z_tot of an insulating ionic fluid such as water between electrodes is a complex subject.¹⁷ The most general model for the complex impedance of an electrode in ionic solution is typically modeled as the Randle circuit, which is shown in Fig. ​Fig.22.¹⁷ There are two major contributions to the imaginary part of the impedance: the capacitance of the double layer (C_dl), which is purely imaginary and has no dc conductance, and the impedance due to charge transfer resulting in electrochemical reactions at the electrode∕electrolyte interface, which can be modeled as a contact resistor (R_CT), which is given by the Butler–Volmer equation, which describes the I-V characteristic curve when electrochemical reactions occur at the electrode,¹⁸ in series with a complex Warburg impedance (Z_W) which represents injected charge transport near the electrode;¹⁹ more details can be found in Ref. ²⁰. Since we applied a 10 mV rms ac voltage with no dc offset in our measurements, electrochemical reactions are negligible, which means no electrochemical charge transfer occurred and as a result R_CT goes to infinity. We have drawn a gray box around the elements connected to the Warburg impedance branch of the circuit to show that they are negligible in our analysis.Open in a separate windowFigure 2The equivalent circuit of the nanoelectrodes in contact with water lying atop an insulating SiO₂ film which covers a silicon substrate. The elements in the gray boxes can be ignored in our measurements since there is no hydrolysis at low voltage, while the elements within the dotted box are coupling reactances to the underlying p-doped silicon wafer.In the case of no direct charge injection, the electrodes are coupled by the purely capacitive dielectric layer impedance C_dl to the solvent and are also coupled capacitively by the dielectric SiO₂ film capacitance C_ox to the underlying p-doped silicon semiconductor. We model the semiconductor as a purely resistive material with bulk resistivity ρ_Si. The value of C_dl∕area is on the order of ϵϵ_oκ, where ϵ is the dielectric constant of water (about 80) and κ is the Debye screening parameter of the counterions in solution: κ=ϵϵokBT∕e2Σici∞zi2,²⁰ where ci∞ is the bulk ion concentration of charge z_i. At our salt molarity of 50 mM (1∕2 Tris∕Borate∕EDTA (TBE) buffer), C_dl is approximately 30 μF∕cm² using 1∕κ∼1 nm.In Fig. ​Fig.3,3, we show the ac impedance measurements between pairs nanoelectrodes for both dry and TBE buffer wet nanochannels. The electrodes are capacitively coupled to the underlying silicon substrate through an oxide capacitor C_ox. We model the doped silicon wafer as pure resistors, so there is an R₁ that connects both C_ox, and each C_ox is connected to the ground with an R₂. Curve fitting was done by using the 3SPICE circuit emulation code (VAMP Inc., Los Angeles, CA). We therefore obtained the following parameters for the dry curve: C_ox=1.32 nF, R₁=17.5 μΩ, and R₂=32.8 kΩ. R₁ is not sensitive in the fit as long as it is smaller than the impedance of C_ox. Given ρ_Si of the wafer of 1–10 Ω cm, R₂ should be on the order of 10³ Ω, which is slightly smaller than our fitting results. The same parameters for the wafer coupling parameters were then used for fitting the impedance measurements for wet channels. For TBE buffer solution in the nanochannel, curve fitting yields C_dl=50 pF and R_sol=10⁵ Ω. However, given the dimension of our nanochannels, we should get a transverse resistance R∼10⁹ Ω. One possible explanation for this difference is that the evaporated SiO₂ film which was put over the PMMA is porous and allows buffer to penetrate the oxide film,²¹ but given that the film is only 25 nm thick this would at most increase the cross section by one order of magnitude. However, it is known that there is a high fractional presence of mobile counterions associated with the charged channel walls.²² To calculate exact conductance contribution from the surface charges is a tricky business, but since the surface-to-volume ratios in our nanochannels are much greater than the slits, a larger conductance enhancement can be expected, and more work needs to be done.Open in a separate windowFigure 3ac impedance spectra of TBE buffer solution in a transchannel measurement between adjacent pairs of nanoelectrodes separated by 135 μm. The red circles are data for a dry channel and the solid red line is the fit to the model shown in the upper right hand corner. The green squares and dashed green line are for a nanochannel wet with TBE buffer.We have presented a way to fabricate a nanochannel integrated with electrodes. This technology opens up opportunities for electronic detection of charged polymers. With our techniques to fabricate nanoelectrodes with nanochannels, it should be possible to include integrated electronics with nanofludics, allowing the electronic observation of a single DNA molecule at high spatial resolution. However, the present design has problems. Most of the ac went through the silicon wafer instead of the solution. To enhance the sensitivity, we need either to increase the ratio of current going through the liquid to the current going through the wafer or to have a circuit design that picks up the changes in C_dl and R_sol.  相似文献   

The Animated Muse: An Interpretive Program for Creative Viewing     

Austin Clarkson  Douglas Worts 《Curator: The Museum Journal》2005,48(3):257-280

Explore a Painting in Depth, an experiment presented in the Canadian Collection of the Art Gallery of Ontario, consisted of a booth that offered seating for two visitors and, opposite them, The Beaver Dam, a 1919 landscape painting by the Canadian artist J. E. H. MacDonald. In a 12‐minute audio‐guided Exercise for Exploring, visitors were invited to engage in a creative process with the imagery of the painting. This paper sketches how the experiment evolved, presents the background of the Exercise for Exploring, and surveys the effects of the exhibit on a wide range of visitors. The question is raised: How can facilitating visitors' creative responses to artworks be part of the museum's educational mandate and its arsenal of interpretive resources? More broadly: Do strategies that foster and privilege visitor creativity, as well as honor the creativity of artists, affect the accessibility and relevance of the museum for the general public?  相似文献   

Candidates’ use of informal communication on social media reduces credibility and support: Examining the consequences of expectancy violations     

Olivia M. Bullock  Austin Y. Hubner 《Communication Research Reports》2020,37(3):87-98

ABSTRACT

This experiment (N= 476) investigates how individuals evaluate political candidates who use informal communication on social media. We use expectancy violations theory (EVT) to predict that informal communication will lead to negative evaluations. Our results suggest that politicians’ use of informal communication on social media leads to expectancy violation, which decreases perceived credibility and lessens intention to support a candidate. This effect was not moderated by sex (male versus female) or age (young versus old) of the candidate, nor of participants being the same sex as the candidate. These findings suggest that political figures should use informal communication on social media with caution.  相似文献   

BIBLIOGRAPHY OF WAR MEDICINE     

Austin RB 《Bulletin of the Medical Library Association》1943,31(4):390-393

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Developing and designing online engineering ethics instruction for international graduate students     

Katherine A. Austin  Greta J. Gorsuch  William D. Lawson  Byron P. Newberry 《Instructional Science》2011,39(6):975-997

The present project embarked on an educational intervention, consisting of a series of online ethics learning modules, to aid international graduate students in overcoming the acculturation barriers to understanding and inculcating normative ethical obligations associated with engineering practice and research in the United States. A fundamental initial step in the process of helping international, as well as domestic, engineering graduate students embrace ethical obligations is to provide clear instruction on fundamental engineering ethical principles and values relevant in the United States. Most institutes of higher education do not have a cohesive approach to basic graduate engineering ethics instruction, much less materials that have been calibrated for international students (National Science Foundation, , 2009). Herein the authors describe our instructional intervention, as well as to document the development, design, and assessment of the learning modules intended to provide students with a framework for learning ethical precepts and applying them in the engineering field. Think-Aloud Protocol and Cognitive Task Analysis results were used to improve the content modules and learning experience. Initial pilot findings indicate that the content modules increased student knowledge acquisition compared to pre-test performance, indicating a step-forward in the formulation of a useful learning tool for graduate engineering ethics instruction.  相似文献   

A Quantitative Synthesis of Methodology in the Meta-Analysis of Single-Subject Research for Students with Disabilities: 1985–2009     

Daniel M. Maggin  Breda V. O'Keeffe  Austin H. Johnson 《Exceptionality》2013,21(2):109-135

The purpose of this review was to examine the methods used to conduct meta-analyses of single-subject research involving students with and at-risk for disabilities. Specifically, the procedures used for preparing, aggregating, analyzing, and evaluating single-subject data across 68 primary syntheses were examined. In addition to these methodological and reporting issues, the present review also considered various characteristics of syntheses to determine their overall prevalence and focus. Results of the review indicated that the publication rate of single-subject meta-analyses has increased considerably in recent years, focusing equally on students with high- and low-incidence disabilities. This review revealed considerable variability in the methods and procedures used to synthesize single-subject research. Based on these findings, suggestions for future single-subject meta-analyses were made.  相似文献   

Et in arcadia ego: Politics and learning in Ghana     

Dennis Austin 《Minerva》1975,13(2):236-269

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Language and mathematical education     

Austin  J. L.  Howson  A. G. 《Educational Studies in Mathematics》1979,10(2):161-197

Educational Studies in Mathematics -  相似文献   

Project soar     

Marion Austin 《Roeper Review》2013,35(2):39-40

A project exemplifies how a gifted program can work in a rural area.  相似文献   

2009年度人物亚军:中国工人     

Austin Ramzy  寒星 《英语辅导》2010,(3)

去年12月,美国《时代》周刊(TIME)2009年度人物榜出炉。美联储主席本·伯南克(BenBernanke)当选该杂志年度人物,而中国工人作为榜单上的唯一群体,荣升亚军宝座。世界的目光犹如聚光灯般投射到中国工人身上,而肖红霞、黄冬艳、彭春霞、邱小院等人的名字和笑容在一夜之间传遍了世界。这群来自深圳的普通工人成为千千万万勤劳坚韧的中国工人的代表。也许就个体来说,他们再平凡不过,然而所有平凡人的努力积聚起来,就能创造出让世人为之惊叹的伟大与奇迹。不要怨叹自己过于平庸、没有大作为,实际上,伟大很可能就如同做好本分工作那么简单。  相似文献