Stella W. Pang

Effects of nanoparticle size and cell type on high sensitivity cell detection using a localized surface plasmon resonance biosensor.

A localized surface plasmon resonance (LSPR) effect was used to distinguish cell concentration on ordered arrays of Au nanoparticles (NPs) on glass substrates. Human-derived retinal pigment epithelial RPE-1 cells with flatter bodies and higher confluency were compared with breast cancer MCF-7 cells. Nanosphere lithography was used to form Au NPs with average diameters of 500 and 60 nm in order to compare cell detection range, resonance peak shift, and cell concentration sensitivity. A larger cell concentration range was detected on the larger 500 nm Au NPs compared to 60 nm Au NPs (8.56 × 10(3)-1.09 × 10(6) vs. 3.43 × 10(4)-2.73 × 10(5)cells/ml). Resonance peak shift could distinguish RPE-1 from MCF-7 cells on both Au NPs. RPE-1 cells consistently displayed larger resonance peak shifts compared to MCF-7 cells until the detection became saturated at higher concentration. For both types of cells, higher concentration sensitivity in the range of ~10(4)-10(6)cells/ml was observed on 500 nm compared to 60 nm Au NPs. Our results show that cells on Au NPs can be detected in a large range and at low concentration. Optimal cell sensing can be achieved by altering the dimensions of Au NPs according to different cell characteristics and concentrations.

Large-scale Topographical Screen for Investigation of Physical Neural-Guidance Cues

A combinatorial approach was used to present primary neurons with a large library of topographical features in the form of micropatterned substrate for high-throughput screening of physical neural-guidance cues that can effectively promote different aspects of neuronal development, including axon and dendritic outgrowth. Notably, the neuronal-guidance capability of specific features was automatically identified using a customized image processing software, thus significantly increasing the screening throughput with minimal subjective bias. Our results indicate that the anisotropic topographies promote axonal and in some cases dendritic extension relative to the isotropic topographies, while dendritic branching showed preference to plain substrates over the microscale features. The results from this work can be readily applied towards engineering novel biomaterials with precise surface topography that can serve as guidance conduits for neuro-regenerative applications. This novel topographical screening strategy combined with the automated processing capability can also be used for high-throughput screening of chemical or genetic regulatory factors in primary neurons.

High sensitivity plasmonic biosensor based on nanoimprinted quasi 3D nanosquares for cell detection

Quasi three-dimensional (3D) plasmonic nanostructures consisting of Au nanosquares on top of SU-8 nanopillars and Au nanoholes on the bottom were developed and fabricated using nanoimprint lithography with simultaneous thermal and UV exposure. These 3D plasmonic nanostructures were used to detect cell concentration of lung cancer A549 cells, retinal pigment epithelial (RPE) cells, and breast cancer MCF-7 cells. Nanoimprint technology has the advantage of producing high uniformity plasmonic nanostructures for such biosensors. Multiple resonance modes were observed in these quasi 3D plasmonic nanostructures. The hybrid coupling of localized surface plasmon resonances and Fabry-Perot cavity modes in the quasi 3D nanostructures resulted in high sensitivity of 496 nm/refractive index unit. The plasmonic resonance peak wavelength and sensitivity could be tuned by varying the Au thickness. Resonance peak shifts for different cells at the same concentration were distinct due to their different cell area and confluency. The cell concentration detection limit covered a large range of 5 × 10(2) to 1 × 10(7) cells ml(-1) with these new plasmonic nanostructures. They also provide a large resonance peak shift of 51 nm for as little as 0.08 cells mm(-2) of RPE cells for high sensitivity cell detection.

Electrode modifications to lower electrode impedance and improve neural signal recording sensitivity.

OBJECTIVE Although electrode size should be miniaturized to provide higher selectivity for neural signal recording and to avoid tissue damage, small sized electrodes induce high impedance, which decreases recording quality. In this work, the electrode surface was modified to increase the effective surface area to lower the electrode impedance and to improve the neural signal detection quality by optimizing plasma conditions. APPROACH A tetrafluoromethane (CF4) plasma was used to increase the effective surface area of gold electrode sites of polyimide-based neural probes. In vitro electrode impedance and in vivo neural signal recording and stimulation were characterized. MAIN RESULTS For 15 μm diameter (dia.) electrode size, the average surface roughness could be increased from 1.7 to 22 nm after plasma treatment, and the electrode impedance was decreased by 98%. Averaged background noise power in the range of 1 to 1000 Hz was decreased to -106 dB after the 30 μm dia. electrodes were plasma modified-lower than the noise level of -86 dB without plasma treatment. Neural probes with plasma-modified electrode sites of 15 and 30 μm dia. were implanted to the anterior cingulate cortex (ACC) region for acute recording of spontaneous and electrical evoked local field potential (LFP) of neural signals. Spontaneous LFP recorded in vivo by the plasma-modified electrodes of 30 μm dia. was two times higher compared to electrodes without treatment. For a stimulation current of 400 μA, electrically evoked LFP recorded by the plasma-modified electrodes was seven times higher than those without plasma exposure. SIGNIFICANCE A controllable technology was developed to increase the effective surface area of electrodes using a CF4 plasma. Plasma-modified electrodes improved the quality of the neural probe recording and more sensitive to record spontaneous and evoked LFP in the ACC region.

Effects of three-layered nanodisk size on cell detection sensitivity of plasmon resonance biosensors

The double resonance plasmonic biosensors based on Au nanodisks (NDs) with a thin SiO2 spacer between the top and bottom Au layers were employed to detect MCF-7 breast cancer cells. The hybridized modes between the localized surface plasmon resonance of Au NDs and the gap coupling resonance of NDs with the Au film underneath have been observed. These multiple metallic layer NDs exhibit higher sensitivity than the common single metallic layer NDs. The extinction spectra showed double resonance bands that could be tailored by varying the ND size. Three sizes of multiple layer NDs ranging from 60 to 200 nm diameter (dia.) were generated and their refractive sensitivity to the surrounding media were analyzed for cell detection. Nanodisks with 120 dia. showed the highest refractive sensitivity up to 230 nm/refractive index unit. These sensors could be used to detect a broad range of MCF-7 cells from a low cell concentration down of 1.0×10(3)cells/ml up to a high cell concentration of 1.7×10(7) cells/ml.

A Unidirectional Cell Switching Gate by Engineering Grating Length and Bending Angle.

On a microgrooved substrate, cells migrate along the pattern, and at random positions, reverse their directions. Here, we demonstrate that these reversals can be controlled by introducing discontinuities to the pattern. On “V-shaped grating patterns”, mouse osteogenic progenitor MC3T3-E1 cells reversed predominately at the bends and the ends. The patterns were engineered in a way that the combined effects of angle- and length-dependence could be examined in addition to their individual effects. Results show that when the bend was placed closer to one end, migration behaviour of cells depends on their direction of approach. At an obtuse bend (135°), more cells reversed when approaching from the long segment than from the short segment. But at an acute bend (45°), this relationship was reversed. Based on this anisotropic behaviour, the designed patterns effectively allowed cells to move in one direction but blocked migrations in the opposing direction. This study demonstrates that by the strategic placement of bends and ends on grating patterns, we can engineer effective unidirectional switching gates that can control the movement of adherent cells. The knowledge developed in this study could be utilised in future cell sorting or filtering platforms without the need for chemotaxis or microfluidic control.

A microfabricated low-profile wideband antenna array for terahertz communications

While terahertz communications are considered to be the future solutions for the increasing demands on bandwidth, terahertz equivalents of radio frequency front-end components have not been realized. It remains challenging to achieve wideband, low profile antenna arrays with highly directive beams of radiation. Here, based on the complementary antenna approach, a wideband 2 × 2 cavity-backed slot antenna array with a corrugated surface is proposed. The approach is based on a unidirectional antenna with a cardiac radiation pattern and stable frequency characteristics that is achieved by integrating a series-resonant electric dipole with a parallel-resonant magnetic dipole. In this design, the slots work as magnetic dipoles while the corrugated surface radiates as an array of electric dipoles. The proposed antenna is realized at 1 THz operating frequency by stacking multiple metallized layers using the microfabrication technology. S-parameter measurements of this terahertz low-profile metallic antenna array demonstrate high efficiency at terahertz frequencies. Fractional bandwidth and gain are measured to be 26% and 14 dBi which are consistent with the simulated results. The proposed antenna can be used as the building block for larger antenna arrays with more directive beams, paving the way to develop high gain low-profile antennas for future communication needs.

A 750–1000 GHz

A wideband THz H-plane dielectric horn antenna based on silicon (Si) technology is proposed in this paper. The antenna can be integrated with the planar structure circuit and the dielectric ridge waveguide. To fabricate the proposed antenna, the deep reactive ion etching high-resistivity Si fabrication process is used. The size of the proposed antenna is 3.13 × 4 × 0.1 mm3. The operating frequency of the antenna ranges from 750 to 1000 GHz, which corresponds to a fractional impedance bandwidth of 28.6%. The antenna has a narrow beamwidth in the H-plane and a high gain. To test this antenna, the characterization of the metal waveguide diagonal horn for measurement is analyzed. Then the non-contact measurement method is applied to measure the designed dielectric horn. The simulated radiation efficiency of the antenna is higher than 80% while the measured gain of the antenna is larger than 8 dBi. Measured H-plane radiation patterns from the proposed antenna are presented and show reasonable agreement with the simulated results.

H

In this paper, dielectric ribbon waveguides (DRWs) are designed to work at 750-1000 GHz. In this frequency band, the Deep Reactive Ion Etching (DRIE) of high resistivity silicon fabrication process is selected to fabricate the DRW. Our experiments show that the average attenuation constant of DRW is merely 0.107dB/mm at 750-1000GHz. Good agreements between the measured and simulated results are observed.

-Plane Dielectric Horn Based on Silicon Technology

In this paper, four types of silicon based THz dielectric waveguide are introduced. The silicon based THz dielectric waveguides are all fabricated by DRIE technology. The losses of these dielectric waveguides are very low.