A CBET Nugget Notable Accomplishments from CBET Awards

Photonic Crystal Biosensors Brian Cunningham  -  University of Illinois Urbana-Champaign

Background:  The specific aims of the research project are to investigate means for advancing the state-of-the-art in photonic crystal biosensor performance and applications, with the overall goal of achieving detection resolution of an individual protein molecule using an image-based detection instrument.  With this level of sensitivity, label-free detection can be equivalent to fluorescent-label-based detection approaches and make a major impact on the time, effort, and accuracy of a large percentage of biomolecular and cell-based assays performed today. Methodology:  Sensor designs are being approached first by computer simulation using Rigorous Coupled Wave Analysis (RCWA) and Finite Difference Time Domain (FDTD) methods, followed by fabrication and testing of the structure.  The design goals are to produce more narrow resonant spectra, higher surface/volume ratio, and higher electromagnetic field interaction with adsorbed material than first-generation designs.  The incorporation of different materials to increase surface electromagnetic field intensity, and structures to maximize the interaction of the field with adsorbed biomolecules will be demonstrated. Results include:      O Demonstration of a new photonic crystal sensor design that incorporates a nanoporous replicated periodic surface structure to obtain a 5x sensitivity gain - - representing by far the most sensitive photonic crystal biosensor structure.     O Large-area nanoreplica molding fabrication of the nanoporous photonic crystal biosensor, and demonstration of uniform biosensor microplates and application to detection of small molecule drug compounds.  Devices have recently been demonstrated on flexible plastic film substrates for low-cost, disposable biosensor applications.     O Design, fabrication, and evaluation of photonic crystal biosensor structures with resonant wavelengths in the ultraviolet (UV) spectrum, for enhanced surface sensitivity relative to IR wavelength photonic crystals.     O Integration of photonic crystal biosensors with microfluidic flow channels, and multiplexed image-based detection of biochemical binding for reduction of assay volume, including an industry standard-format 96-well microplate with integrated microfluid channels.     O Self-referencing label-free assay methods and image processing to accurately compensate for biochemical assay artifacts such as nonspecific binding and bulk refractive index effects for detecting protein or small molecule binding.     O Development of nanotextured dielectric surfaces to increase immobilized protein binding density and detection sensitivity by (so far) up to 16x.     O Label-free imaging of live human breast cancer cells, and screening the interaction of cancer cells against a library of 61 plant extracts for possible apoptosis-inducing drug compounds.

A.  96-well microplate incorporating microfluidic channels with integrated photonic crystal optical biosensors capable of performing 88 biochemical assays at once.

B.  Magnified views of the detection region formed in plastic by a nanoreplica molding process.       C.  Scanning Electron Microscope photo of the photonic crystal surface with a nanostructured dielectric thin film coating that increases surface area for protein adsorption, thereby increasing detection sensitivity.

D.  Label-free images of human breast cancer cells detected by the photonic crystal biosensor.  Here, the sensor is used to rapidly determine whether potential drug compounds either increase the rate of cancer cell proliferation, or lead to cell death by apoptosis.  The sensor and detection instruments are capable of detecting single cells and monitoring large cell populations in their culture environment.

Credit:  Brian Cunningham, University of Illinois Urbana-Champaign

Scientific Uniqueness:  The sensors developed in this project represent a new class of biosensors based upon optical devices known as "photonic crystals" that have higher sensitivity than previous commercially available methods by a wide margin.  Through the proper application of photonic crystal design and fabrication, elctromagnetic fields may be confined and concentrated, so as to enhance the interaction between light and biological material in contact with the photonic crystal.  While many varieties of optical biosensors have been proposed and demonstrated, photonic crystal biosensors have demonstrated a unique combination of high sensitivity, inexpensive fabrication over large surface areas, and the ability to address a wide range of assay applications.  Because a photonic crystal surface does not allow lateral propagation of light, many independent measurements may be performed on a single photonic crystal surface without crosstalk, leading to the ability to perform label-free biochemical assays with throughput that has not been possible before. Impact on Industry and/or Society:  The project is focused primarily on the development of biosensors and detection instrumentation for use in the fields of pharmaceutical development and patient diagnostic testing.  The key attributes for acceptance of new technolgy in these fields are sensitivity (how low of a concentration of a chemical or gene may be detected), cost per test, and throughput (the number of tests that can be performed at once).  The impact of the research is the development of sensitive and accurate tools that will be used in the life science field to study the interaction of proteins involved in disease, and to the study of how drug compounds interact with proteins and cells.  Such tools are used to quickly determine the potential effectiveness and adverse side effects of pharmaceutical treatments at an early stage, before expensive clinical trials are conducted.  Such sensors are also used for clinical screening of patient samples for the presence of biomarkers that may indicate the presence of a disease before other symtoms are observed. Work is notable because the Cunningham Group has developed sensor designs and fabrication methods that enable improved detection sensitivity by more than an order of magnitude, with devices inexpensively produced in plastic.  The research contributes to the development of photonic crystal sensor detection instrumentation.  Combined, the biosensors and detection instruments enable high throughput detection of biochemical binding kinetics, imaging large arrays of biochemical tests, and imaging detection of individual cells - - resulting in the highest throughput biosensor detection system yet demonstrated. This work is multidisciplinary. The conception and execution of the project requires findamental knowledge of the intereaction of electromagnetic waves with materials and structures with feature sizes in the nanometer range, the ability to perform and analyze computer simulations to test sensor designs before they are fabricated, fabrication of submicron structures using novel methods that include nanoreplica molding, application of surface chemistry layers to impart specific detection functionality to the sensors, and the ability to perform biochemical assays with proteins and live cancer cells.  The graduate students supported by this grant are required to master each of these areas. This work represents transformative research.  With sufficient sensitivity, combined with low cost and high assay throughput, label free detection using photonic crystal biosensors could replace a wide range of assays using labels (for example, radiolabels and fluorophors).  Label-free methods reduce complexity and increase accuracy in the fields of life science research, pharmaceutical discovery, diagnostic testing, and environmental detection. - - Primary Strategic Outcome Goal:  Discovery:  Foster research that will advance the frontiers of knowledge, emphasizing areas of greatest opportunity and potential benefit and establishing the nation as a global leader in fundamental transformational science and engineering. - - Secondary Strategic Outcome Goal:  Learning:  Cultivate a world-class, broadly inclusive science and engineering workforce, and expand the scientific literacy of all citizens. This work addresses the goals of the NSF Strategic Plan 2006-2011 and fits in with the strategic outcome goal for advancing fundamental discoveries in science and engineering.  The project improves on nanotechnology for drug delivery by designing materials that can interact with and utilize natural cellular machinery for improved delivery.

Program Officer:		Leon Esterowitz
NSF Award Number:		0427657
Award Title:		SENSORS: Photonic Crystal Biosensors
PI Name:		Brian Cunningham
Institution Name:		University of Illinois at Urbana-Champaign
Program Element:		7236
CBET Nugget:		FY 2007

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This Nugget was Updated on 26 September 2008.