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

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.     

Short report Further efforts in validating a 'spurning scale' for teachers

The present study represents our continuing effort to validate a 'spurning scale' for teachers, based on a model on spurned helpers' reactions. Three approaches were used to examine the validity of the scale: the spurning scores of teachers working with more achieving students vs the scores of teachers teaching less achieving students. The relationships between the spurning scores and job satisfaction and turnover scores; and the relationships between the spurning scores and scores indicative of stress arising from interactions with one's students and supervisor. Serving teachers in Hong Kong responded to a questionnaire that contained the variables of interest. The results provided further evidence for the validity of the scale.     

Specification Search for Identifying the Correct Mean Trajectory in Polynomial Latent Growth Models

This study investigated the optimal strategy for model specification search under the latent growth modeling (LGM) framework, specifically on searching for the correct polynomial mean or average growth model when there is no a priori hypothesized model in the absence of theory. In this simulation study, the effectiveness of different starting models on the search of the true mean growth model was investigated in terms of the mean and within-subject variance-covariance (V-C) structure model. The results showed that specifying the most complex (i.e., unstructured) within-subject V-C structure with the use of LRT, ΔAIC, and ΔBIC achieved the highest recovery rate (>85%) of the true mean trajectory. Implications of the findings and limitations are discussed.     

Effects of Technology-Mediated Vocabulary Intervention for Third-Grade Students with Reading Difficulties

Abstract

In this experimental study, we examined the effects of a technology-mediated intervention to improve students’ understanding of academic vocabulary and its impact on measures of vocabulary and comprehension. The Vocabulators program was implemented in two states involving 24 teachers and 200 third-grade students identified as in need of supplemental vocabulary instruction. Individual students within each classroom were randomly assigned to treatment (n?=?100) or typical instructional practices (n?=?100) conditions. In the treatment condition, students received, on average, 29 lessons on vocabulary and comprehension. Results of linear regression analyses showed statistically significant and practical effects on experimenter-developed proximal measures of decoding (ES = 0.52), expressive vocabulary (ES = 0.78), receptive vocabulary (ES = 0.51), and near transfer measures of understanding vocabulary in sentences (ES = 0.65), and informational text comprehension (ES = 0.28). Group performance did not differ statistically on near transfer measures of sentence verification with vocabulary and narrative text comprehension as well as distal standardized measures of general vocabulary or reading comprehension. Findings suggest the potential impact of technology-based vocabulary/comprehension lessons to supplement typical instruction.     

Using SEM to Analyze Complex Survey Data: A Comparison between Design-Based Single-Level and Model-Based Multilevel Approaches

Both ad-hoc robust sandwich standard error estimators (design-based approach) and multilevel analysis (model-based approach) are commonly used for analyzing complex survey data with nonindependent observations. Although these 2 approaches perform equally well on analyzing complex survey data with equal between- and within-level model structures (B. O. Muthén & Satorra, 1995), the performances of these 2 approaches for analyzing multilevel data with unequal between- and within-level structures have not yet been systematically examined. In this study, we extended B. O. Muthén and Satorra's (1995) Muthén, B. O. and Satorra, A. 1995. Complex sample data in structural equation modeling. Sociological Methodology, 25: 267–316. [Crossref], [Web of Science ®] , [Google Scholar] study by comparing these 2 approaches and an additional model-based maximum model for analyzing multilevel data considering number of clusters, cluster size, intraclass correlation, and the equality of different level structures. The simulation results showed the model-based maximum model generally performed well across conditions. This model is also recommended as an alternative for analyzing nonindependent survey data, especially when the information of the higher level model structure is not known.     

A Virtual Learning Environment for Part-Time MASW Students: An Evaluation of the WebCT

This study aims to evaluate the perception of a cohort of social workers studying for a part-time master's program in social work in using the popular Web-based learning platform-World Wide Web Course Tools (WebCT) as a complimentary method of teaching and learning. It was noted that social work profession began incorporating computer technology in its practice long after other professions. Its incorporation into social work teaching came even later. Questionnaires were used to collect views on computer-assisted learning (CAL) and the WebCT. Follow-up, individual in-depth interviews were conducted to obtain further qualitative data to understand the specific conditions under which a virtual learning environment becomes facilitative. It was found that in general students have a positive towards CAL and the WebCT, but they do not think that their education should be entirely Web-based. Teacher-student interactions were still essential to achieve the educational objectives. Nonetheless, the complementary value of the virtual learning environment, that is, a good measure of independence and productivity in their study depends on the students' level of competence and familiarity with the WebCT platform.     

Improving English and Chinese Ad-Hoc Retrieval: A Tipster Text Phase 3 Project Report

Both English and Chinese ad-hoc information retrieval were investigated in this Tipster 3 project. Part of our objectives is to study the use of various term level and phrasal level evidence to improve retrieval accuracy. For short queries, we studied five term level techniques that together can lead to good improvements over standard ad-hoc 2-stage retrieval for TREC5-8 experiments. For long queries, we studied the use of linguistic phrases to re-rank retrieval lists. Its effect is small but consistently positive.For Chinese IR, we investigated three simple representations for documents and queries: short-words, bigrams and characters. Both approximate short-word segmentation or bigrams, augmented with characters, give highly effective results. Accurate word segmentation appears not crucial for overall result of a query set. Character indexing by itself is not competitive. Additional improvements may be obtained using collection enrichment and combination of retrieval lists.Our PIRCS document-focused retrieval is also shown to have similarity with a simple language model approach to IR.     

Serial overshadowing of taste aversion learning by stimuli preceding the target taste

Three experiments tested whether events taking place before a rat has access to a target taste, sucrose, can proactively interfere with the acquisition of a sucrose aversion when sucrose is followed by a lithium chloride injection. Using a serial overshadowing procedure with various delays before lithium injection, proactive interference by a taste (Experiments 1 and 3) and by a novel context (Experiment 2) was found following two conditioning sessions, but not after a single conditioning session. Conversely, overshadowing by a taste given after the target was detectable after a single conditioning trial (Experiment 3) and, thus, indicated that retroactive interference involves a process different from that producing proactive interference. A simulation confirmed that the results are consistent with a modified Rescorla and Wagner (1972) interpretation of Revusky??s (1971) concurrent interference theory of delay learning.