NBTC: Research Areas

Project Title
Nanoscale Optofluidic Devices for Biomolecular Analysis

Research Program
Biomolecular Devices and Analysis

Project #
BDA13

Participating Faculty:	D. Erickson, A. Baeumner, M. Lipson
NBTC Students/Postdocs:	Sudeep Mandal, Sam Nugen
Other Students/Postdocs:	Julie Goddard, Yun Suk Huh, Likun Chen, Brad Schmidt

Objectives
Recent interest in the development of new biosensor technology has been driven by the potential for associating biomarkers with disease states or pharmacological responses, and the need to rapidly diagnose emerging viral threats. To capitalize on these applications successful next generation sensor platforms should be able to: maximize the total number of biomarker targets against which a sample or multiple samples can be interrogated while being sufficiently sensitive and specific so as to enable very low, sub-femtogram level detection without the need for target labeling.

The objective of this program is the development of Nanoscale Optofluidic Sensor Arrays (NOSA) applied to the detection of Dengue virus RNA. The prototype along with a system schematic is shown in Fig. 1 and is based on our recently developed capability to: integrate nanoscale fluidics with optically resonant devices (Erickson, Lipson Labs) and create viral RNA pathogen biosensors (Baeumner Lab).

In the first year of this program (2007) we were able to develop and construct a proof of concept prototype for the NOSA platform and a target immobilization method to efficiently orient DNA oligonucleotide probes in silicon substrates. In the first 8 months of this project year we have again made significant progress, specifically we have

(1 – Whole Team) Demonstrated the specific detection of Dengue DNA sequences using the NOSA device as shown in Fig. 2.

(2 – Julie Goddard, Sam Nugen) Developed a technique for “functionalization nanopatterning” that enables us to target the immobilization of biomolecules directly on the optical cavity of our device, as shown in Fig. 3).

(3 – Julie Goddard, Sudeep Mandal) Designed nucleic acid probes for detection of two serotypes of H1N1 and two serotypes of H3N2 Influenza A virus, and developed surface immobilization techniques and microfluidic hybridization assays that allow serotype specific detection.

(4 – Yun Suk Huh) Developed a new “Optofluidic SERS” technique for detecting Dengue virus RNA. Using this technique we demonstrated a limit of detection of 10pM in less than 5 minutes.

(5 – Sam Nugen). Investigated further methods for the immobilization of biomolecules on silicon and other substrates and developed a new method to adhere gold to surfaces using cystamine monolayers.

Methods
Methods used to accomplish this project include: numerical prototyping using finite difference, time domain simulation, electron-beam and photolithography lithography to fabricate the sensors and microfluidics, infrared spectral interrogation to optically probe the devices and detect the presence of a biding event, and dendrimer based immobilization chemistries for probe immobilization. Further details on the methods used here are available in the references cited in the captions of Figures 1 through 3.

Summary
The goal of this program is to develop a new approach to viral RNA detection that combines the exceptional sensitivity achievable with nanosystems with the parallelity offered by traditional microarray devices. Since the initiation of this project in January 2007, we have constructed a prototype device, developed a new approach to nanopatterning of biomolecular probes, demonstrated serotype specific detection of synthetic Dengue Virus RNA using both the NOSA device and a new optofluidic SERS method, extended our work to develop a compatible detection assay for influenza.

Accomplishments

Demonstrated improved sensitivity for serotype specific detection of synthetic Dengue Virus RNA (Figure 2)
Developed a new technique for biomolecular patterning over nanophotonic devices with nanoscopic precision.
Developed a new method for Dengue Virus detection using Optofluidic SERS.

Fig. 1: Nanoscale Optofluidic Sensor Arrays (NOSA) (a) 3D illustration of a NOSA sensing element. It consists of a 1D photonic crystal micro-cavity which is evanescently coupled to a Si waveguide. (b) The electric field profile for the fundamental TE mode propagating through an air-clad Si waveguide on SiO2. (c) SEM of a NOSA device array. It illustrates how this architecture is capable of two dimensional multiplexing, thus affording a large degree of parallelism. (d) Actual NOSA chip with an aligned PDMS fluidic layer on top.

For details see [Mandal, S., Erickson, D., “Nanoscale Optofluidic Sensor Arrays” Optics Express, 16, 1623-1631 (2008)].

Fig. 2: Detection of Dengue Virus Sequences. Figure shows average resonator redshifts in response to: (first) immobilization of dendrimers and DNA capture probes (second) Complementary sequence, serotype 1 (third) Non-complementary sequence serotype 2. Redshifts are shown in nanometers (average redshift for complementary DNA was 200 pm).

Fig. 3. Functionalization Nanopatterning. One of our major accomplishments this year was the development of a technique for targeting biomolecular directly in the cavity of an optically resonant device. This leads to a much lower limit of detection. This image shows the parylene patterning technique at various stages in the process (a) without UV/base treatment, and (b) with UV/base treatment. (c) SEM image after removal of parylene. Scale bar represents 2 mm.

For details see [Goddard, J., Mandal, S., Nugen, S., Baeumner, A., Erickson, D. “Patterning of Nucleic Acid Probes in Optical Nanocavities” Submitted (2008).]

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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