Photonic Crystal Label-Free Biosensors
A new class of optical biosensors based on the unique properties of Photonic Crystals has been recently developed by the Cunningham Group and by SRU Biosystems, a company co-founded by Prof. Cunningham in 2000. A Photonic Crystal label-free biosensor is comprised of a periodic arrangement of dielectric material in two or three dimensions. If the periodicity and symmetry of the crystal and the dielectric constants of the materials used are chosen appropriately, the Photonic Crystal will selectively couple energy at particular wavelengths, while excluding others.
To create a biosensor, a Photonic Crystal may be optimized to provide an extremely narrow resonant mode whose wavelength is particularly sensitive to modulations induced by the deposition of biochemical material on its surface. A sensor structure, shown below, consists of a low refractive index plastic material with a periodic surface structure that is coated with a thin layer of high refractive dielectric material. Device structures based on linear gratings and two-dimensional gratings (i.e. arrays of holes, posts, or veins arranged in checkerboard or hexagonal close-packed grids along the sensor surface) have been demonstrated. The sensor is measured by illuminating the surface with white light, and collecting the reflected light from different locations on the sensor. The biosensor design enables a simple manufacturing process to produce sensor sheets in continuous rolls of plastic film that are hundreds of meters in length. The mass manufacturing of a biosensor structure that is measurable in a noncontact mode over large areas enables the sensor to be incorporated into single-use disposable consumable items such as 96, 384, and 1536-well standard microplates and microarray slides, thereby making the sensor compatible with standard fluid handling infrastructure employed in most laboratories.
For label-free detection, the sensor operates by measuring changes in the wavelength of reflected light as biochemical binding events take place on the surface. For example, when a DNA spot is deposited on the sensor surface, an increase in the reflected wavelength occurs only on the locations on the Photonic Crystal surface where the DNA deposited mass density results in a change in surface dielectric permittivity, and the amount of wavelength shift is proportional to the deposited mass density. The readout instrument is able to detect deposited mass changes on the surface with resolution less than 1 pg/mm2, and a spatial resolution of ~4 microns per pixel.
Figure 1. Device cross section schematic and SEM photo (plan view) of a photonic crystal biosensor based on a 1-dimensional linear grating structure.
Figure 2. Schematic of the photonic crystal biosensor readout method, in which a broadband light source (such as a light bulb or LED) illuminates the biosensor surface at normal incidence and a narrow band of wavelength are reflected. A spectrometer records changes in the reflected wavelength as biomaterial attaches to the photonic crystal surface.
Figure 3. Photo of nanoreplica molded plastic photonic crystal biosensors incorporated into standard format 96-, 384-, and 1536-well microplates. Microplates are the most commonly used liquid handling format in life science research, and integration of biosensors with microplates enables biosensor experiments to be performed at high throughput and low cost per assay. The biosensors are manufactured from long, continuous sheets of plastic film with manufacturing methods that allow the sensor surface to produced on a square yardage basis – thus allowing the sensor to be used for single-use disposable applications.
- "Colorimetric Resonant Reflection as a Direct Biochemical Assay Technique," B.T. Cunnigham, P. Li, B. Lin, and J. Pepper, Sensors and Actuators B, Volume 81, p. 316-328, January 2002.
- "A Label-Free High Throughput Optical Technique for Detecting Small Molecule Interactions," B. Lin, J. Pepper, P. Li, H. Pien, and B.T. Cunningham, Biosensors and Bioelectronics, Vol. 17, No. 9, p. 827-834, September 2002.
- "A Plastic Colorimetric Resonant Optical Biosensor for Multiparallel Detection of Label-Free Biochemical Interactions," B.T. Cunningham, B. Lin, J. Qiu, P. Li, J. Pepper, and B. Hugh, Sensors and Actuators B, Vol. 85, number 3, pp219-226, November 2002.
- "Compact label-free biosensor using VCSEL-based measurement system," C.F.R. Mateus, M.C.Y. Huang, J.E. Foley, P.R. Beatty, P. Li, B.T. Cunningham, and C.J. Chang-Hasnain, IEEE Photonics Technology Letters, Vol 16, No 7, 1712-1714, 2004.
- "Enhancing the Surface Sensitivity of Colorimetric Resonant Optical Biosensors," B.T. Cunningham, J. Qiu, P. Li, and C. Baird, Sensors and Actuators B, Volume 87, Issue 2, Pages 365-370, December 2002.
- "A New Method for Label-Free Imaging of Biomolecular Interactions," P. Li, B. Lin, J. Gerstenmaier, and B.T. Cunningham, Sensors and Actuators B, Vol. 99, p. 6-13, (2004).
- "Label-Free Assays on the BIND System," B.T. Cunningham, P. Li, S. Schulz, B. Lin, C. Baird, J. Gerstenmaier, C. Genick, F. Wang, E. Fine, and L. Laing, Journal of Biomolecular Screening, Vol 9, p. 481-490, (2004).
- "A Label-Free Biosensor-Based Cell Attachment Assay for Characterization of Cell Surface Molecules," B. Lin, P. Li, and B.T. Cunningham, Sensors and Actuators B, Vol 114, No. 2, p. 559-564, (2006).
- "Label-free Detection of Biomolecular Interactions: Applications in Proteomics and Drug Discovery," B.T. Cunningham and L.L. Laing, Expert Reviews in Proteomics, Vol 3, No. 3, p. 271-281, (2006).
- "Photonic Crystal Optical Biosensor Incorporating Structured Low-Index Porous Dielectric," I.D. Block, L.L. Chan, and B.T. Cunningham, Sensors and Actuators, B: Chemical, v 120, n 1, Dec 14, 2006, p 187-193.
- "A Self- Referencing Method for Microplate Label-Free Photonic Crystal Biosensors," L.L. Chan, P.Y. Li, D. Puff, and B.T. Cunningham, IEEE Sensors Journal, Vol. 6, No. 6, p. 1551-1556, 2006.
- "Self-Referenced Assay Method for Photonic Crystal Biosensors: Application to Small Molecule Analytes," L.L. Chan, P.Y. Li, D. Puff, and B.T. Cunningham, Sensors and Actuators B, Vol. 120, No. 2, p.392-398, 2007.
- "A label-free photonic crystal biosensor imaging method for detection of cancer cell cytotoxicity and proliferation," L. Chan, S. Gosangari, K. Watkin, and B.T. Cunningham, Apoptosis, Vol. 12, No, 6, p. 1061-1068, 2007.
- "Combined Enhanced Fluorescence and Label-Free Biomolecular Detection with a Photonic Crystal Surface," P.C. Mathias, N. Ganesh, L.L. Chan, and B.T. Cunningham, Applied Optics, Vol. 46, No. 12, p. 2351-2360, 2007.
- "A 96-well microplate incorporating a replica molded microfluidic network integrated with photonic crystal biosensors for high throughput kinetic biomolecular interaction analysis," C. J. . Choi and B.T. Cunningham, Lab On A Chip, Vol. 7, p. 550-556, 2007.]
- (*W) "Label-free imaging of cancer cells using photonic crystal biosensors and application to cytotoxicity screening of a natural compound library," L.L. Chan, S. Gosangari, K.L. Watkin, and B.T. Cunningham, Sensors and Actuators B, Vol. 132, p. 418-425, 2008.
- "A sensitivity model for predicting photonic crystal biosensor performance," I.D. Block, N. Ganesh, M. Lu, and B.T. Cunningham, IEEE Sensors, Vol. 8, No. 3, p. 274-280, 2008.
- "High Sensitivity Photonic Crystal Biosensor Incorporating Nanorod Structures for Enhanced Surface Area," W. Zhang, N. Ganesh, I.D. Block and B.T. Cunningham, Sensors and Actuators B, Vol. 131, p. 279-284, 2008.
- "High Sensitivity Plastic-Substrate Photonic Crystal Biosensor," I.D. Block, M.F. Pineda, C.J. Choi, and B.T. Cunningham, IEEE Sensors Journal, Vol. 8, No. 9, p. 1546-1547, 2008.
- "Advantages and application of label-free detection assays in drug screening," B.T. Cunningham and L.G. Laing, Expert Opinions in Drug Discovery, Vol. 3, No. 8, p. 891-901, 2008. [Ref#58]
- "General Method for Discovering Inhibitors of Protein-DNA Interactions using Photonic Crystal Biosensors," L.L. Chan, M.F. Pineda, J. Heeres, P. Hergenrother, and B T. Cunningham, ACS Chemical Biology, Vol. 3, No. 7, p. 437-448, 2008.
- "Rapid label-free selective detection of porcine rotavirus using photonic crystal biosensors," M.F. Pineda, L.L. Chan, T. Kuhlenschmidt, M. Kuhlenschmidt, and B.T. Cunningham, IEEE Sensors Journal, Vol. 9, No. 4, p. 470-477, 2009.
- "A method for identifying small molecule aggregators using photonic crystal biosensor microplates," L.L. Chan, E.A. Lidstone, K.E. Finch, J.T. Heeres, P.J. Hergenrother, and B.T. Cunningham, Journal of the Association for Laboratory Automation (JALA), Vol. 14, No. 6, p. 348-359, 2009.
- "Optimizing the spatial resolution of photonic crystal label-free imaging," I.D. Block and B.T. Cunningham, Applied Optics, Accepted, November 2009.
- "Photonic Crystal Surfaces as a General Purpose Platform for Label-Free and Fluorescent Assays," B.T. Cunningham, Journal of the Association of Laboratory Automation, accepted November 2009 (invited).
- "Label-free detection of soybean rust spores using photonic crystal biosensor," R. Vittal, W. Zhang, L.L. Chan, B.T. Cunningham, and G. Hartman, Phytopathology Vol. 99, No. 6, S136, 2009. [Ref#77]
- "Identifying modulators of protein-protein interactions using photonic crystal biosensors," J.T. Heeres, S.-H. Kim, B.J. Leslie, E.A. Lidstone, B.T. Cunningham, and P.J. Hergenrother, Journal of the American Chemical Society, Accepted, November 2009.