Fabian Pease

Targeted cell detection based on microchannel gating

Currently, microbiological techniques such as culture enrichment and various plating techniques are used for detection of pathogens. These expensive and time consuming methods can take several days. Described below is the design, fabrication, and testing of a rapid and inexpensive sensor, involving the use of microelectrodes in a microchannel, which can be used to detect single bacterial cells electrically (label-free format) in real time. As a proof of principle, we have successfully demonstrated real-time detection of target yeast cells by measuring instantaneous changes in ionic impedance. We have also demonstrated the selectivity of our sensors in responding to target cells while remaining irresponsive to nontarget cells. Using this technique, it can be possible to multiplex an array of these sensors onto a chip and probe a complex mixture for various types of bacterial cells.

A Microfluidic Platform for Characterization of Protein–Protein Interactions

Traditionally, expensive and time consuming techniques such as mass spectrometry and Western Blotting have been used for characterization of protein-protein interactions. In this paper, we describe the design, fabrication, and testing of a rapid and inexpensive sensor, involving the use of microelectrodes in a microchannel, which can be used for real-time electrical detection of specific interactions between proteins. We have successfully demonstrated detection of target glycoprotein-glycoprotein interactions, antigen-antibody interactions, and glycoprotein-antigen interactions. We have also demonstrated the ability of this technique to distinguish between strong and weak interactions. Using this approach, it may be possible to multiplex an array of these sensors onto a chip and probe a complex mixture for various types of interactions involving protein molecules.

PHOTOELECTRON EMISSION STUDIES IN CsBr AT 257 nm

CsBr/Cr photocathodes were found [1,2] to meet the requirements of a multi-electron beam lithography system operating with a light energy of 4.8 eV (257nm). The fact that photoemission was observed with a light energy below the reported 7.3 eV band gap for CsBr was not understood. This paper presents experimental results on the presence of intra-band gap absorption sites (IBAS) in CsBr thin film photo electron emitters, and presents a model based on IBAS to explain the observed photoelectron emission behavior at energies below band gap. A fluorescence band centered at 330 nm with a FWHM of about 0.34 eV was observed in CsBr/Cr samples under 257 nm laser illumination which can be attributed to IBAS and agrees well with previously obtained synchrotron photoelectron spectra[1] from the valence band of CsBr films.

Electrical Detection of Proteins and DNA using Bioactivated Microfluidic Channels: Theoretical and Experimental Considerations

In order to detect diseases like cancer at an early stage while it still may be curable, its necessary to develop a diagnostic technique which can rapidly and inexpensively detect protein and nucleic acid biomarkers, without making any sacrifice in the sensitivity. We have developed a technique, based on the use of bioactivated microfluidic channels integrated with electrodes for electrical sensing, which can be used to detect protein biomarkers, target cells, and DNA hybridization. In this paper, we discuss the theoretical detection limits of this kind of sensor, and also discuss various experimental considerations in the electrical characterization of our device. In particular, we discuss the temperature dependence, the impedance drift, the noise sources, and various methods for optimizing the signal to noise ratio.

Evaluation of electron energy spread in CsBr based photocathodes

Photocathodes with relatively low energy spread ( 150A∕cm2) with very long lifetime (approximately hundreds of hours/spot). Experimental results of the photoelectron energy spread obtained in CsBr films deposited on both metal and InGaN substrates will be presented in this paper.

Aluminum-Germanium eutectic bonding for 3D integration

Low-temperature Aluminum-Germanium (Al-Ge) eutectic bonding has been investigated for monolithic three-dimensional integrated circuits (3DIC) applications. Successful bonds using Al-Ge bilayer films as thin as 157 nm were achieved at temperatures as low as 435 °C, when applying 200 kPa down-pressure for 30 minutes. The liquid phase of the eutectic composition ensured a seamless and void-free bond. The fracture energy of the Al-Ge bond (630 nm thick) was measured to be Gc = 50.5 ± 12.7 J/m2, using double cantilever beam thin-film adhesion measurement technique. An array of silicon islands was attached onto an amorphous SiO2 wafer using low-temperature Al-Ge bonding. These islands could be used to form devices on upper layers of monolithically integrated 3DICs.

Direct electrical detection of target cells on a microfluidic biochip

Pathogenic bacterial cell detection is currently performed using techniques such as culture enrichment and various plating methods, which are expensive and can take up to several days. In this study, we describe the design, fabrication, and testing of a rapid and inexpensive sensor for detection of target cells electrically in real-time. The sensor operates with the use of microelectrodes integrated in a micro-channel. As a proof of principle, we have successfully demonstrated real-time detection of target yeast cells with a concentration of 107 cells/ml. We have also demonstrated the selectivity of our sensors in responding to target cells while remaining irresponsive to non-target cells. We also perform theoretical modeling in order to determine the ultimate detection limit of the sensor. Based on our modeling results, proper optimization of the sensor can yield detection limits approaching the single cell level.

Electron beam induced conductivity in polymethyl methacrylate, polyimide, and SiO2 thin films

Electron beam induced conductivity (EBIC) is one sensitive parameter that controls the charging of insulating materials under electron beam irradiation. In an earlier work [J. Vac. Sci. Technol. B 21, 2638 (2003)], we reported the measurement of EBIC in polymethyl methacrylate (PMMA) and thermal SiO2 thin films using an external bias method. The thin films under test were sandwiched between a silicon substrate and a metal electrode. One important observation is that the exposed region in the PMMA resist is ohmic regardless of the bias polarity. However, the EBIC in the metal-thermal oxide-silicon structure is highly asymmetric under opposite bias polarities. A model involving the internal emission of secondary electrons was proposed to interpret the asymmetric EBIC in thermal oxide. In this study, we extend the EBIC measurements to deposited SiO2 thin film and another polymeric material, polyimide. By putting the deposited oxide between symmetric metal electrodes, we validated the conjecture of the intern...

Low-temperature Al–Ge bonding for 3D integration

Low-temperature aluminum–germanium (Al–Ge) bonding has been investigated for monolithic three-dimensional integrated circuit (3DIC) applications. As upper layer devices of a monolithic 3DIC are fabricated in situ, a suitable technique for providing high-quality semiconducting material without inflicting damage to underlying circuits below is needed. Here, the authors demonstrate a method of attaching high-quality single-crystal Si (100) and Ge (100) islands (3–3000 μm in size) onto amorphous SiO2 substrates using both eutectic (435 °C) and subeutectic (400 °C) Al–Ge bonding. The 30 min, 3DIC compatible process utilizes Al–Ge bilayer films as thin as 157 nm to form void-free bonds strong enough to withstand SmartCut® hydrogen splitting of the donor wafer. The fracture energy of the Al–Ge bond was measured to be GC = 50.5 ± 12.7 J/m2, as measured by the double cantilever beam thin-film adhesion measurement technique.

A cesium bromide photocathode excited by 405 nm radiation

In several applications, such as electron beam lithography and X-ray differential phase contrast imaging, there is a need for a free electron source with a current density at least 10 A/cm2 yet can be shaped with a resolution down to 20 nm and pulsed. Additional requirements are that the source must operate in a practical demountable vacuum (>1e-9 Torr) and be reasonably compact. In prior work, a photocathode comprising a film of CsBr on metal film on a sapphire substrate met the requirements except it was bulky because it required a beam (>10 W/cm2) of 257 nm radiation. Here, we describe an approach using a 405 nm laser which is far less bulky. The 405 nm laser, however, is not energetic enough to create color centers in CsBr films. The key to our approach is to bombard the CsBr film with a flood beam of about 1 keV electrons prior to operation. Photoelectron efficiencies in the range of 100–1000 nA/mW were demonstrated with lifetimes exceeding 50 h between electron bombardments. We suspect that the elec...