Plasmon tuning and local field enhancement maximization of the nanocrescent.

We present a systematic numerical study of plasmon resonance of the nanocrescent. We show that by varying the nanocrescent geometry, the plasmon resonance peak can be tuned into the near-infrared and local field enhancement can be increased significantly, with maximum enhancement of the electric field amplitude of approximately 100 for realistic geometric parameters. Because of its wide tunability, high local field enhancement, and geometry which utilizes both sharp features and intra-particle coupling, the nanocrescent is a structure well suited for in vivo cellular imaging as well as in vitro diagnostic applications.

Integrated microfluidic cell culture and lysis on a chip.

We present an integrated microfluidic cell culture and lysis platform for automated cell analysis that improves on systems which require multiple reagents and manual procedures. Through the combination of previous technologies developed in our lab (namely, on-chip cell culture and electrochemical cell lysis) we have designed, fabricated, and characterized an integrated microfluidic platform capable of culturing HeLa, MCF-7, Jurkat, and CHO-K1 cells for up to five days and subsequently lysing the cells without the need to add lysing reagents. On-demand lysis was accomplished by local hydroxide ion generation within microfluidic chambers, releasing both proteinacious (GFP) and genetic (Hoescht-stained DNA) material.

Quantized plasmon quenching dips nanospectroscopy via plasmon resonance energy transfer.

We observed quantized plasmon quenching dips in resonant Rayleigh scattering spectra by plasmon resonance energy transfer (PRET) from a single nanoplasmonic particle to adsorbed biomolecules. This label-free biomolecular absorption nanospectroscopic method has ultrahigh molecular sensitivity.

Microfluidic self-assembly of tumor spheroids for anticancer drug discovery.

Creating multicellular tumor spheroids is critical for characterizing anticancer treatments since it may provide a better model than monolayer culture of in vivo tumors. Moreover, continuous dynamic perfusion allows the establishment of physiologically relevant drug profiles to exposed spheroids. Here we present a physiologically inspired design allowing microfluidic self-assembly of spheroids, formation of uniform spheroid arrays, and characterizations of spheroid dynamics all in one platform.

Peptide-nanoparticle hybrid SERS probes for optical detection of protease activity.

Real-time in situ detection of active proteases is crucial for early-stage cancer screening and cell signaling pathway study; however, it is difficult to achieve using fluorescence or radioactive probes at volumes below 1 nL. Here we demonstrated a hybrid optical probe by incorporating nanocrescent particle and peptides with artificial tag molecules. We performed a proof-of-concept study using prostate specific antigen (PSA), one of the most prominent prostate cancer markers, and a serine protease present in patients' seminal fluid and serum.

An artificial liver sinusoid with a microfluidic endothelial-like barrier for primary hepatocyte culture.

Primary hepatocytes represent a physiologically relevant model for drug toxicity screening. Here, we created a biologically inspired artificial liver sinusoid with a microfluidic endothelial-like barrier having mass transport properties similar to the liver acinus. This unit consisted of a cord of hepatocytes (50 x 30 x 500 microm) fed by diffusion of nutrients across the microfluidic endothelial-like barrier from a convective transport vessel (10 nL/min).

Open-access microfluidic patch-clamp array with raised lateral cell trapping sites.

A novel open-access microfluidic patch-clamp array chip with lateral cell trapping sites raised above the bottom plane of the chip was developed by combining both a microscale soft-lithography and a macroscale polymer fabrication method. This paper demonstrates the capability of using such an open-access fluidic system for patch-clamp measurements. The surface of the open-access patch-clamp sites prepared by the macroscale hole patterning method of soft-state elastic polydimethylsiloxane (PDMS) is examined; the seal resistances are characterized and correlated with the aperture dimensions.

Dynamic single cell culture array.

It is important to quantify the distribution of behavior amongst a population of individual cells to reach a more complete quantitative understanding of cellular processes. Improved high-throughput analysis of single cell behavior requires uniform conditions for individual cells with controllable cell-cell interactions, including diffusible and contact elements. Uniform cell arrays for static culture of adherent cells have previously been constructed using protein micropatterning techniques but lack the ability to control diffusible secretions.

Single-cell enzyme concentrations, kinetics, and inhibition analysis using high-density hydrodynamic cell isolation arrays.

High-quality single-cell data are required for a quantitative systems biology description of cellular function. However, data of this type are difficult and time-consuming to collect using traditional techniques. We present a robust and simple microfluidic method for trapping single cells in large arrays to address this problem.

Spectral tuning of localised surface plasmon-polariton resonance in metallic nano-crescents.

The utilisation of plasmonic effects in metallic nanostructures is gaining importance for applications in molecular sensing. Of special interest is the local field enhancement effect, which enables surface-enhanced Raman scattering and significantly boosts the sensitivity of the Raman technique. For in vivo biological research, the ability to excite the resonance of localised surface plasmon-polaritons within the biological window is often desired.

Biologically inspired artificial compound eyes.

This work presents the fabrication of biologically inspired artificial compound eyes. The artificial ommatidium, like that of an insect's compound eyes, consists of a refractive polymer microlens, a light-guiding polymer cone, and a self-aligned waveguide to collect light with a small angular acceptance. The ommatidia are omnidirectionally arranged along a hemispherical polymer dome such that they provide a wide field of view similar to that of a natural compound eye.

Microfluidic alignment of collagen fibers for in vitro cell culture.

Three dimensional gels of aligned collagen fibers were patterned in vitro using microfluidic channels. Collagen fiber orientation plays an important role in cell signaling for many tissues in vivo, but alignment has been difficult to realize in vitro. For microfluidic collagen fiber alignment, collagen solution was allowed to polymerize inside polydimethyl siloxane (PDMS) channels ranging from 10-400 microm in width.

Time-resolved optical sensing of oligonucleotide hybridization via Au colloidal nanoparticles.

Au nanoparticles have distinctive absorption spectra whose peak position or particle plasmon resonance wavelength is highly sensitive to molecule adsorption on their surfaces. Spherical Au nanoparticles are surface-modified by amino-functionalized self-assembly-monolayer and used as optical probes in the fluorescence-label-free spectroscopic detection of sub-nanomole oligonucleotides. Time-resolved studies of the immobilization and hybridization of oligonucleotides on the surface of Au nanoparticles were carried out.

Optofluidic control using photothermal nanoparticles.

Photothermal metallic nanoparticles have attracted significant attention owing to their energy-conversion properties. Here, we introduce an optofluidic application based on a direct optical-to-hydrodynamic energy conversion using suspended photothermal nanoparticles near the liquid-air interface. Using light beams with submilliwatt power, we can drive and guide liquid flow in microfluidic channels to transport biomolecules and living cells at controlled speeds and directions.

Nanoliter scale microbioreactor array for quantitative cell biology.

A nanoliter scale microbioreactor array was designed for multiplexed quantitative cell biology. An addressable 8 x 8 array of three nanoliter chambers was demonstrated for observing the serum response of HeLa human cancer cells in 64 parallel cultures. The individual culture unit was designed with a "C" shaped ring that effectively decoupled the central cell growth regions from the outer fluid transport channels.