NBTC: Research Areas

Project Title
Micro & Nanostructures for Molecular Detection, Separation and Analysis

Research Program
Biomolecular Devices and Analysis

Project #
BDA2

Participating Faculty:	H. Craighead, R. Austin, B. Baird, H. Hoch, D. Lin, J. Lis, D. Soloway, L. Walker
NBTC Students/Postdocs:	E. A.Strychalski, B. Cipriany, S.-M. Park, J. Mannion, P. Zhu, A. Depolite
Other Students/Postdocs:	L. Bellan, J. Moran-Mirabal, C. Tan, P. Waggoner

Objectives
The goal of our research is to study new approaches for the creation and application of nanostructures to be used for molecular detection, separation and analysis. Our interests focus on investigations of fundamental physical properties of nanoscale devices that can be utilized for detection, identification and manipulation of biomolecules. Detailed investigations of single DNA molecules and its polymer properties have been a significant part of our work, leading to increasingly sophisticated devices for single molecule studies of a variety of biological systems relevant to biotechnology applications. Nanoscale optical and electrical devices have also been explored for detecting individual molecules and analyzing dynamic systems at the single molecule level. By combining fluidics and simple electronics we are also miniaturizing systems of biochemical analysis and selection.

Methods
Varied, nanoscale geometries were designed and tested for use in micro/nanofluidics. Channels with diameters between 100 and 500nm have permitted manipulation and detection capabilities on the single molecule level. We have scaled these down to considerably smaller dimensions of a few tens of nm and utilized these for optical and electrical measurements of DNA. Our optical methods enabled us to distinguish folded molecules and investigate the dynamics of their unfolding and diffusive motion in channels and slits. While electron beam and optical lithography is frequently used to create these structures, our group is also working on techniques to create nanodevices, including the use of electrospun nanofibers and etched and sealed trenches.

The use of simple sub-wavelength metallic apertures, or zero-mode waveguides, continues to be exploited for molecular investigations. These devices are useful for observing chemical reactions in free solution or surfaces as well as dynamic properties in reactions.

Carbon nanotubes are exquisitely well-defined nanostructures that have been widely studied. We are working to integrate these into fluidic systems and explore their capabilities for observation of biomolecules.

We have worked on processes for incorporating electrical heaters in microfluidics as pumps and for selected-area thermal processing. These have become critical components of integrated systems for electrospray ionization mass spectrometry and systems for multiplexed selection and evolution of nucleic acid aptamers.

Summary
Our group continues experimenting on new nanoscale fabrication techniques and we have shown to reliably create and utilize structures with dimensions of tens of nm for observation of biological systems. The work has been featured, for example, on the cover on the journal Nanotechnology. The use of nanofluidic systems, zero mode waveguides, nanofibers, carbon nanotubes, and nanoslits have been demonstrated in numerous collaborative efforts and described in the listed publications. Integrated systems for lab-on-a-chip analytical and biomolecular selection have been demonstrated.

Accomplishments

Advances in technology for nanofludic channel formation and integration with optics and electronics
Studies of dynamics of DNA confirmation in nanofluidic systems
Demonstration of integrated lab-on-a-chip methods for mass spectroscopy and selection of biomolecules

Figure 1: Observation of entropically driven unfolding of a DNA molecule in a nanochannel. Left: Time trace of a fluorescently labeled DNA molecule spontaneously unfolding in a nanofluidic channel. The degree of folding is measured by observing two levels of fluorescent intensity. Right: Extracted folded and total molecular length as a function of time. This has been modeled by a simple model for entropic forces in the nanochannel.
Figure 2: Schematic showing concept of electronic detection of elongated DNA in a nanochannel. Left: Top view of device. DNA flows through a nanochannel in an elongated state, and eventually passes over a carbon nanotube detector. Right: Side view of device. The negatively charged DNA backbone causes a shift in the local solution potential, but only if the nanotube is within the Debye screening distance from the molecule. We have developed a process for incorporating nanotubes into channels with depths on the order of a few tens of nm that should allow reliable electrical detection. This compliments our work on optical measurements in nanochannels.
Figure 3: (A) This chip contains electrodes for electrochemical pumping and electrospray ionization, an SU-8 electrospray tip, and microchannels. (B) An optical micrograph of interdigitated gold electrodes. After the wet etch, neither defect nor damage was found on the COC surface. (C) An SEM image of the SU-8 electrospray tip. (D) Image of an integrated system for multiplexed SELEX also incorporating an electrode array for selective elution of bound material

This material is based upon work supported in part by the STC Program of the National Science Foundation under Agreement No. ECS-9876771. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation.

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