Aamer Mahmood

Circulating tumor cell detection using a parallel flow micro-aperture chip system

We report on-chip isolation and detection of circulating tumor cells (CTCs) from blood samples using a system that integrates a microchip with immunomagnetics, high-throughput fluidics and size-based filtration. CTCs in a sample are targeted via their surface antigens using magnetic beads functionalized with antibodies. The mixture is then run through a fluidic chamber that contains a micro-fabricated chip with arrays of 8 μm diameter apertures. The fluid runs parallel to the microchip while a magnetic field is generated underneath to draw the beads and cells bound to them toward the chip surface for detection of CTCs that are larger than the apertures and clear out free beads and other smaller particles bound to them. The parallel flow configuration allows high volumetric flow rates, which reduces nonspecific binding to the chip surface and enables multiple circulations of the sample fluid through the system in a short period of time. In this study we first present models of the magnetic and fluidic forces in the system using a finite element method. We then verify the simulation results experimentally to determine an optimal flow rate. Next, we characterize the system by detecting cancer cell lines spiked into healthy human blood and show that on average 89% of the spiked MCF-7 breast cancer cells were detected. We finally demonstrate detection of CTCs in 49 out of 50 blood samples obtained from non-small cell lung cancer (NSCLC) patients and pancreatic cancer (PANC) patients. The number of CTCs detected ranges from 2 to 122 per 8 mL s of blood. We also demonstrate a statistically significant difference between the CTC counts of NSCLC patients who have received therapy and those who have not.

An Evanescent-mode Cavity Resonator Based Thermal Sensor

This paper reports the use of an evanescent-mode cavity resonator as a temperature sensor. The frequency loading is achieved by a capacitive post in the center of the cavity confining the electric field in a small volume. The resonant frequency of a loaded evanescent-mode cavity is related to the capacitance of the loading mechanism. As a sensing mechanism, a rectangular array of thermally actuated bilayered microcantilever beams on a silicon substrate has been fabricated using conventional microfabrication processes and placed inside the resonator. A temperature change causes the microcantilevers to deflect, changing the parasitic capacitance of the cavity and hence the resonant frequency of the resonator. Loaded microwave cavities have been fabricated using a layer by layer stereolithographic process and then metallized. The Si hosting the cantilevers is attached to the cavity. The resonant frequency of the sensor is monitored as a function of temperature and varies from 11.34 GHz at room temperature to 12 GHz at 90degC. At room temperature, the sensor has a temperature coefficient of frequency (TCF) of 0.029%/degC.

Micromachined infrared sensor arrays on flexible polyimide substrates

This paper presents work on micromachined infrared detectors on flexible substrates. The detectors are made of semiconducting yttrium-barium-copper-oxide (YBCO) and are built on a 40-50 /spl mu/m layer of polyimide (PI58578G) that serves as the flexible substrate. Two variants of micromachined infrared detectors have been fabricated The first variant employs a mesa structure in which self-supporting Ti arms hold up the detector pixel. The second variant has a more planar topology with the detector being supported by a layer of silicon nitride. Surface micromachining is used to isolate the detectors from the substrate. After fabrication the polyimide is peeled off the carrier wafer and the devices are packaged and characterized. The 40/spl times/40 /spl mu/m/sup 2/ microbolometers have responsivities ranging from 7.4/spl times/10/sup 3/ V/W to 10/sup 4/ V/W and detectivities ranging from 6.6/spl times/10/sup 5/ cm-Hz/sup 1/2//W to 10/sup 8/ cm-Hz/sup 1/2//W. These results are comparable to those obtained for devices made on a rigid silicon substrate. The effect of substrate heating is also investigated and found not to affect the detector performance.

A Device-Level Vacuum-Packaging Scheme for Microbolometers on Rigid and Flexible Substrates

This paper reports on the design, fabrication, and characterization of device-level vacuum-packaged microbolometers on rigid Si wafers and flexible polyimide substrates. Semiconducting yttrium barium copper oxide (commonly referred to as YBCO) serves as the bolometric material. Operating micromachined bolometers in vacuum reduces the thermal conductance Gth from the detector to the substrate. If flexibility of the substrate is not to be sacrificed, then the vacuum packaging needs to be done at the device level. Here, the microbolometers are fabricated on a silicon nitride support membrane, isolated from the substrate using surface micromachining. Suitable materials as well as various dimensions in the vacuum cavity are determined using finite-element method (FEM)-based CoventorWARE. A vacuum cavity made of Al2O3 has been designed. The thermal conductance Gth of bolometers with the geometry implemented in this work is the same for devices on rigid and flexible substrates. The theoretical value of Gth was calculated to be 4.0 x 10-6 W/K for devices operating in vacuum and 1.4 x 10-4 W/K for devices operating at atmospheric pressure. Device-level vacuum-packaged microbolometers on both rigid Si and flexible polyimide substrates have been fabricated and characterized for optical and electrical properties. A low thermal conductance of 1.1 X 10-6 W/K has been measured six months after fabrication, which implies an intact vacuum cavity.

High-throughput immunomagnetic cell detection using a microaperture chip system

We report a microchip system based on a combination of immunomagnetic separation, microfluidics, and size-based filtration for high-throughput detection of rare cells. In this system, target cells bind to magnetic beads in vitro and flow parallel to a microchip with flow rates of milliliters/minute. A magnetic field draws the bead-bound cells toward the microchip, which contains apertures that allow passage of unbound beads while trapping the target cells. The cells captured on the chip can be investigated clearly under a microscope and released from the chip for further analysis. We first characterize the system by detecting cancer cell lines (MCF-7 and A549) in culture media. We then demonstrate detection of 100 MCF-7 cells spiked in 7.5 mL of human blood to simulate detection of circulating tumor cells present in cancer patient blood samples. On average, 85% of the spiked cells were detected. We expect this system to be highly useful in a wide variety of clinical as well as other applications that seek rare cells.

Optoelectronic measurement of x-ray synchrotron pulses: A proof of concept demonstration

Optoelectronic detection using photoconductive coplanar stripline devices has been applied to measuring the time profile of x-ray synchrotron pulses, a proof of concept demonstration that may lead to improved time-resolved x-ray studies. Laser sampling of current vs time delay between 12 keV x-ray and 800 nm laser pulses reveal the ∼50 ps x-ray pulse width convoluted with the ∼200 ps lifetime of the conduction band carriers. For GaAs implanted with 8 MeV protons, a time profile closer to the x-ray pulse width is observed. The protons create defects over the entire depth sampled by the x-rays, trapping the x-ray excited conduction electrons and minimizing lifetime broadening of the electrical excitation.

Nanoelectrode arrays for measuring Sympathetic Nervous Activity

This paper reports on the use of arrays of nanoelectrodes to measure activity of the Sympathetic Nervous System. Measurements of the Sympathetic Nervous Activity (SNA) have not been easy; primarily because of poor signal-to-noise ratio (SNR). We report improved SNR of SNA measurements achieved by the use of novel Planar Nanoelectrode Arrays (PNA). Nano scale features on the electrodes provide increased contact area with the host nerve reducing the limiting (Johnson) noise. These electrodes are fabricated using standard CMOS compatible fabrication techniques on a high resistivity silicon substrate and used to measure SNA in test animals. For comparison, traditional wire electrodes were used simultaneously to measure the same signal. The PNAs consistently exhibit significant improvement in the SNR of the measured SNA (35.71 dB vs. 25.08 dB for the wire electrode). Moreover, the PNAs are capable of recording events lost in the noise floor of the wire electrodes.

Quantifying heat produced during spontaneous combustion of H 2 /O 2 nanobubbles

Microcombustors provide many advantages over electrochemical cells as sources to power microsystems. A microfabricated thermal sensor (resistance thermometer/RTD type) has been employed to measure the amount of heat produced due to the combustion of H<inf>2</inf>/O<inf>2</inf> nanobubbles created by electrolysis in such a microcombustor. It has been observed that combustion occurs above a threshold frequency of 15 kHz. The local surface heat produced initially increased linearly with frequency but at higher frequencies, it showed a non-linear tapering increase. An average surface heat value of 8×10⁴ W/m² was measured, which was in close agreement with the theoretical power of 1×10⁵ W/m² produced from the H<inf>2</inf>/O<inf>2</inf> combustion obtained using the steady-state current value.

Picosecond X-ray Sensor

A coplanar stripline detector has been developed for picosecond resolution of x-ray synchrotron pulses. When triggered by synchronized 100 fs laser pulses, this detector measures the x-ray pulse waveform with 1 ps resolution, a 100-fold improvement compared to standard pump-probe experiments at synchrotron sources. The detectors have been fabricated with CMOS compatible microfabrication processes. Time resolution is limited by photocarrier lifetimes, which is typically hundreds of picoseconds in semi-insulating GaAs. Standard implantation techniques, which add defects that serve as trapping sites to produce subpicosecond lifetimes, are insufficient because of the large x-ray absorption depths. Instead, 8 MeV protons that penetrate hundreds of microns are implanted. Strong signals have been measured using focused monochromatic x-ray beams at the Advanced Photon Source (Argonne, IL, USA). Laboratory excitation with 100 fs laser pulses, instead of x-rays, demonstrates the feasibility of this detector. The 1 ps target time resolution allows for x-ray studies in a crucial time regime where laser-induced electronic excitations transfer energy to the atomic lattice.

On the Nonlinear Dynamics of Electromagnetically-Transduced Microresonators

This work investigates the dynamics of electromagnetically-actuated and sensed microresonators. These resonators consist of a silicon microcantilever and a current-carrying metallic wire loop. When placed in a permanent magnetic field, the devices vibrate due to Lorentz interactions. These vibrations, in turn, induce an electromotive force, which can be correlated to the dynamic response of the device. The nature of this transduction process results in an intrinsic coupling between the system’s input and output, which must be analytically and experimentally characterized to fully understand the dynamics of the devices of interest. This paper seeks to address this need through the modeling, analysis, and experimental characterization of the nonlinear response of electromagnetically-transduced microcantilevers in the presence of inductive and resistive coupling between the devices’ input and output ports. A complete understanding of this behavior should enable the application of electromagnetically-transduced microsystems in practical contexts ranging from resonant mass sensing to micromechanical signal processing.Copyright