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A photonic crystal etched into a wafer of silicon

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Summary
We synthesize nanomaterials and study their chemistry, electrochemistry, and optical properties. Our emphasis is on porous silicon-based materials. Current project topics:

•Low-power distributed sensors for environmental toxins and pollutants based on porous Si photonic crystals

•Label-free molecular biosensors based on thin film optical interferometry in porous thin films

•Silicon-based nanodevices for in-vivo detection and treatment of cancerous tumors and eye-related diseases

•Cell-based biosensors and bioreactors incorporating bacterial or mammalian cells with porous photonic crystals

•Digital microfluidics using magnetic porous Si photonic crystals

•Superparamagnetic iron oxide nanoparticles for in-vivo imaging, diagnostics and therapeutics of cancer


Current Projects
Magnetic Iron Oxide Nanoworms for Tumor Targeting and Imaging. These nano-worms are made of magnetic iron oxide (magnetite) coated with a polymer.  The wormlike structure and a speciallized coating allows these nanodevices to find and attach to tumors. Photos: Ji-Ho Park
Engineering Multifunctional Nanoparticles
NIH-Bioengineering Research Partnerships, NIH CCNE Nanotechnology in Cancer Center, the Moores UCSD Cancer Center and the UCSD NanoTUMOR Center, supported by NIH grant U54 CA 119335r
The goal of this project is to synthesize new nanomaterials that can be used to allow the early diagnosis and effective treatment of cancer. We are engineering multifunctional nanoparticles that will exploit biological processes to guide the targeting, self-assembly, and remote actuation of these materials to treat tumors in mouse models of cancer. The multidisciplinary team is led by MIT Bioengineering professor Dr. Sangeeta Bhatia, and it also includes tumor biologist Dr. Erkki Ruoslahti of the Burnham Institute at UC Santa Barbara.

Publications:
Park, J.-H. et al. Magnetic Iron Oxide Nanoworms for Tumor Targeting and Imaging. Adv. Mater. 2008, 20, 1630-1635.

Simberg, D. et al. Biomimetic amplification of nanoparticle homing to tumors. Proc. Natl. Acad. Sci. U. S. A., 2007, 104, 932-936.

Maltzahn, G.v. et al. Nanoparticle Self-Assembly Directed by Antagonistic Kinase and Phosphatase Activities. Adv. Mater., 2007, 19, 3579–3583.

Maltzahn, G.v. et al. Nanoparticle Self-Assembly Gated by Logical Proteolytic Triggers. J. Am. Chem. Soc. 2007, 129, 6064-6065.

Researchers: Ji-Ho Park, Matt Kinsella


Single magnetic porous silicon microparticle delivers a nanogram payload. Delivery of horseradish peroxidase (contained in microparticle indicated by the arrow) to a droplet containing a colorimetric enzymatic substrate is accomplished by manipulation of the particle using a small magnet. This methodology presents an alternative to channel-based microfluidic systems. Thomas, J. C., Pacholski, C. & Sailor, M. J. "Delivery of Nanogram Payloads Using Magnetic Porous Silicon Microcarriers." Lab Chip 2006, 6, 782 - 787.
Microfluidics with Porous Si Chaperones
NSF-Division of Materials Research (NSF-DMR 0452579), NIH CCNE Nanotechnology in Cancer Center, the Moores UCSD Cancer Center and the UCSD NanoTUMOR Center
One of the challenges faced by nanotechnology involves the manipulation of minescule amounts of liquid. There is an increasing need to do this, as the required time and cost of many medical and environmental analyses is directly proportional to sample volume. Fifteen years ago, the concept of the "lab on a chip" evolved as a marriage of the methods used by analytical chemists and microbiologists with the tools developed in the semiconductor industry for microfabrication. In the world of microfluidics, the bucket is often preferable to the pipe; as the sample volume becomes smaller, the number of molecules that stick to the insides of a microchannel becomes a significant fraction of the total molecules in the sample. This problem spawned the so-called "lab-on-a-drop" concept. A sphere has the lowest ratio of surface area to volume, and if a droplet containing the sample of interest can be manipulated without it coming into contact with the walls of its container, the amount of material lost can be minimized. In this project, we use micron-sized, nanostructured particles of porous Si as manipulators. The particles can carry a nano payload or surround a much larger liquid droplet. The particles contain superparamagnetic iron oxide, and application of a magnetic field allows them to be manipulated. The method provides a general means for manipulating small volumes of liquids without a microfluidic container or use of a pump.

References:
1. Dorvee, J. R.; Sailor, M. J.; Miskelly, G. M. "Digital microfluidics and delivery of molecular payloads with magnetic porous silicon chaperones," Dalton Trans. 2008, 721
2. Thomas, J. C., Pacholski, C. & Sailor, M. J. "Delivery of Nanogram Payloads Using Magnetic Porous Silicon Microcarriers." Lab Chip 2006, 6, 782 - 787.
3. Park, J.-H. et al. "Local Heating of Discrete Droplets Using Magnetic Porous Silicon-Based Photonic Crystals." J. Am. Chem. Soc. 2006, 128 7938-7946.
4. Dorvee, J. R., Derfus, A. M., Bhatia, S. N. & Sailor, M. J. "Manipulation of liquid droplets using amphiphilic, magnetic 1-D photonic crystal chaperones." Nature Mater. 2004, 3, 896-899.

Some leading references for lab-on-a-drop:
1. Millman, J. R., Bhatt, K. H., Prevo, B. G. & Velev, O. D. Anisotropic particle synthesis in dielectrophoretically controlled microdroplet reactors. Nat. Mater. 4, 98-102 (2005).
2. Kotz, K. T., Gu, Y. & Faris, G. W. Optically addressed droplet-based protein assay. J. Am. Chem. Soc. 127, 5736-5737 (2005).
3. Belder, D. Microfluidics with droplets. Angew. Chem. Int. Ed. 44, 3521-3522 (2005).
4. Zheng, B., Tice, J. D., Roach, L. S. & Ismagilov, R. F. A droplet-based, composite PDMS/glass capillary microfluidic system for evaluating protein crystallization conditions by microbatch and vapor-diffusion methods with on-chip X-ray diffraction. Angew. Chem. Int. Ed. 43, 2508-2511 (2004).
5. Srinivasan, V., Pamula, V. K. & Fair, R. B. Droplet-based microfluidic lab-on-a-chip for glucose detection. Anal. Chim. Acta 507, 145-150 (2004).
6. Krupenkin, T. N., Taylor, J. A., Schneider, T. M. & Yang, S. From Rolling Ball to Complete Wetting: The Dynamic Tuning of Liquids on Nanostructured Surfaces. Langmuir 20, 3824 -3827 (2004).
7. Velev, O. D., Prevo, B. G. & Bhatt, K. H. On-chip manipulation of free droplets. Nature 426, 515-516 (2003).
8. Pollack, M. G., Shenderov, A. D. & Fair, R. B. Electrowetting-based actuation of droplets for integrated microfluidics. Lab Chip 2, 96-101 (2002).
9. Jones, T. B., Gunji, M., Washizu, M. & Feldman, M. J. Dielectrophoretic liquid actuation and nanodroplet formation. J. Appl. Phys. 89, 1441-1448 (2001).
10. Aussillous, P. & Quere, D. Liquid marbles. Nature 411, 924-927 (2001).
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Researchers: Chia-Chen Wu.


Waveform encoded into a porous Si photonic crystal. The cross-sectional electron microscope image displays the porous nanostructure that was generated using the current-time waveform depicted at the left. Image credit: Shawn O. Meade.

Spectrally Barcoded Microparticles
Cellular Bioengineering, Inc.
The goal of this project is to construct encoded particles that act as robust, non-toxic taggants. The tags are in the form of microscopic particles containing an elaborate nanostructure that is programmed during electrochemical synthesis to display a complex reflectivity spectrum, referred to as a “Spectral Barcode." The reflectivity spectrum can be decoded using simple, low-power optical spectrometers. We are developing these materials for various applications in high throughput screening and encoded bead-based assays.

References:
1. Meade, S. O.; Yoon, M. S.; Ahn, K. H.; Sailor, M. J., "Porous silicon photonic crystals as encoded microcarriers." Adv. Mater. 2004, 16, (20), 1811-1814.
2. Sailor, M. J.; Link, J. R., "Smart Dust: nanostructured devices in a grain of sand." JCS Chem. Commun. 2005, 1375-1383.
3. Meade, S. O.; Sailor, M. J., "Microfabrication of freestanding porous silicon particles containing spectral barcodes." phys. stat. sol. (RRL) 2007, 1, (2), R71–R73.

Researchers: Michelle Chen



Eryrthrocyte mimics: Polymeric photonic crystals made in a porous Si template exhibit the biocompatibility of a soft polymer and the optical and nanostructure properties of the template. Photo credit: Shawn Meade
Targeted in Vivo Microplatform for Nano Devices
NIH CCNE Nanotechnology in Cancer Center, the Moores UCSD Cancer Center and the UCSD NanoTUMOR Center
http://cancer.ucsd.edu/aboutus/news/ccbrowser/ccbrowser.asp
The goal of this project is to construct micron-sized devices (“mother ships”) that are equipped with nano-sized features capable of homing into cancerous tumors in vivo and performing various tasks in the tumor. These tasks include detecting, identifying, and imaging a tumor, performing measurements on it, and delivering therapies. The system is based on micron-sized, nanostructured porous particles composed primarily of silicon or silicon oxides. The mother ship design concept and silicon-based scaffolding were chosen for a number of reasons: (1) The micron-range size makes it possible to use silicon while retaining its unique engineering features such as optical and radiofrequency reporting properties, high-capacity nano-porous carrier structure, biocompatibility and bioresorbability; (2) We have found that micron-sized particles coated with tumor-specific vascular homing peptides can become lodged in tumor vasculature; (3) Micron-sized particles, unlike nanoparticles, are not taken up by the reticuloendothelial system; (4) The mother ship can be extensively functionalized with nanoparticles, drugs, and imaging agents in a controlled fashion.

Researchers: Matt Kinsella, Sara Alvarez, Jennifer S. Park, Elizabeth Wu, Luo Gu.



Porous Si photonic crystal chemical agent sensors. Roughly the size of the diameter of a human hair, these particles change color in the presence of volatile organic compounds. Photo credit: Anne Ruminski.
Nanosensors Using Porous Photonic Crystals
Elintrix, US Army
The goals of this project are to: (1) develop low-power, sensitive and specific sensors for chemical and biological agents using porous nanomaterials, (2) develop the capability to correct for changes in relative humidity, temperature, and other environmental variables in a low-power, portable package, and (3) demonstrate integratability with conventional electronics. In this project we have:
•Constructed wireless and fiber-based remote sensors for chemical warfare agents, TICs, and pollutants
•Developed "Smart Dust," photonic crystals that detect the presence of molecules as a shift in their characteristic photonic resonance (color change)
Invented Reflective Interferometric Fourier Transform Spectroscopy (RIFTS) that provides automatic drift compensation at the materials level

King, B. H.; Ruminski, A. M.; Snyder, J. L.; Sailor, M. J., "Optical fiber-mounted porous silicon photonic crystals for sensing of organic vapor breakthrough in activated carbon," Adv. Mater. 2007, 19, 4530.

Sailor, M. J.; Link, J. R., "Smart Dust: nanostructured devices in a grain of sand." Chem. Commun. 2005, 1375-1383.

Pacholski, C.; Sartor, M.; Sailor, M. J.; Cunin, F.; Miskelly, G. M., "Biosensing using porous silicon double-layer interferometers: reflective interferometric Fourier transform spectroscopy." J. Am. Chem. Soc. 2005, 127, 11636-11645.

Researchers: Anne Ruminski, Brian King, Adrian Garcia-Sega, Manuel Orosco.
Dr. Jay Snyder, NIOSH



A porous silicon double-layer interferometer contains two porous layers: one with large pores on top of one with small pores. These layers can discriminate molecules based on size, and the optical response of the film provides a self-compensating sensing function. Photo credit: Claudia Pacholski
New functionalized hybrid systems for drug delivery
NSF-Europe Materials Collaboration (NSF-DMR 0503006)
The objective of the project is to develop a vehicle for administration of drugs whose release characteristics can be controlled by intelligent design at the nanoscale. The approach involves infusion of a molecule into a chemically modified matrix of nanocrystalline porous Si or SiO2. Drugs such as the anti-inflammatory dexamethasone, the antibiotic vancomycin, and the analgesic ibuprofen are being incorporated into microscopic particles of porous Si. The high surface area and free volume in porous Si films allows the loading of a large amount of drug. Chemistries to cap the pores with noble metals, polymers, proteins, and silica derived from silanols are being developed, to allow for the slow release of drug under appropriate physiological conditions. The work encompasses new methods of trapping molecules into porous nanostructures, and new methods of monitoring the porous nanostructures using the optical properties of the materials. In particular, we have developed one-dimensional photonic crystals whose spectral signatures can report on the amount or type of drug contained within. Our European partners for this effort are Drs. Bernard Coq, Jean-Marie Devoisselle and Frederique Cunin of the CNRS Laboratoire de Matériaux Catalytiques et Catalyse en Chimie Organique in Montpellier, France. The Montpellier lab has played a major role in the development and commercialization of liposome-based drug delivery materials. The collaboration involves significant student exchange; one of the UCSD student researchers spends approximately 3 months in Montpellier each year.

Cunin, F.; Li, Y. Y.; Sailor, M. J., Nanodesigned pore-containing systems for biosensing and controlled drug release. In Encyclopedia on BioMEMS and Biomedical Nanotechnology, Bhatia, S. N.; Desai, T., Eds. Kluwer: 2004; Vol. in press.
Schwartz, M. P.; Cunin, F.; Cheung, R. W.; Sailor, M. J., "Chemical modification of silicon surfaces for biological applications." Phys. Status Solidi A-Appl. Mat. 2005, 202, (8), 1380-1384.
Pacholski, C.; Sartor, M.; Sailor, M. J.; Cunin, F.; Miskelly, G. M., "Biosensing using porous silicon double-layer interferometers: reflective interferometric Fourier transform spectroscopy." J. Am. Chem. Soc. 2005, 127, 11636-11645.

Researchers: Chia-Chen Wu.


Chemistry of Nanostructured Porous Silicon
NSF-Division of Materials Research (NSF-DMR 0452579)
The goal of this work is to develop an understanding of the effect of surface chemistry on the stability of porous Si photonic crystals. We probe the effects of chemical modification of the porous Si surface on its air and water stability using reactions designed to attach functional species via Si-C bonds. Currently, two related attachment chemistries are studied: electrochemical reduction of alkyl halides and hydrosilylation of terminal alkenes. These chemistries have been found to impart remarkable stability to the porous Si surface relative to Si-H or Si-O surfaces. One of the fundamental questions to be answered is: what is the reason for this improved chemical stability? The project should lead to new understanding of the reactivity of nanocrystalline silicon surfaces. This work should enable advances in the areas of medical diagnostics and therapeutics, remote sensors for pollution monitoring and homeland security applications, information display and optoelectronics.

Researchers: Luo Gu, Manuel Orosco, Sara Alvarez



Human epithelial (HeLa) cells on a "Smart Petri Dish." These cells are used to study cancer, and they are living on a nanostructure made from silicon and plastic known as a photonic crystal. The colors observed can be used to monitor the physiological status of the cells.
Photo credit: Sara Alvarez and Austin Derfus
The "Smart Petri Dish:" Live Cells Grown on Nanostructured Porous Silicon Sensors
La Jolla Interfaces in Science program, funded by the Burroughs Wellcome Fund, Department of Education, Graduate Assistance in Areas of National Need (GANN) program (P200A030163), the San Diego Fellowship Program, NSF-Division of Materials Research (NSF-DMR 0452579)
This project is a multidisciplinary effort involving our group, Lin Chao in the Biology Division at the University of California, San Diego and Sangeeta Bhatia at the Massachusetts Institute of Technology. The objective of this effort is to construct photonic materials capable of monitoring pathogens and viruses in air and in water. In our early work we focused on a soil bacteria, Pseudomonas syringae phaseolicola, and mammalian hepatocyte cells. However, the concepts we have developed define a general method for remote detection of all cell types, including human cell lines (see left image). We have also explored the use of this method for detection of viruses and as a potential method for studying virus propagation in bacterial colonies. Our group focuses on development of the functional photonic materials, which involves chemically modifying nanocrystalline porous Si and polymers templated from this material. Lin Chao and Sangeeta Bhatia provide the expertise in bacterial and mammalian cell biology, respectively. In order to provide specific indicators of cell type, we immobilize adhesion proteins, sugars, and other molecules to improve cell sticking.

Researchers: Manuel Orosco, Sara Alvarez



An optical biosensor for protease activity is constructed from a one-dimensional photonic crystal of porous Si. The porous Si layer is coated with a thin film of zein, a natural hydrophobic protein from maize. Proteolytic cleavage produces small fragments that infiltrate the pores of the photonic crystal, producing a readily observable color change.
Photo credit: Manuel Orosco
Porous-silicon Based Nano Petri Dish for Protease Sensing and Cellular Activity Monitoring
UC Discovery Grant bio06-10564
Private Sponsor
The objective of this project is to develop new tools that can identify bacteria quickly both in the field or in the clinic. The project involves a collaboration with scientists at the Scripps Institution of Oceanography and the Hitachi Chemical Research Center in Irvine, California. We are focusing on a set of molecules that are excreted by bacteria, called proteases. These molecules can indicate the type of bacteria that are present in a water sample. We hope that the sensor we are developing will allow a worker in the field to quickly assess the presence and amount of pathogenic bacteria in a water sample. Other applications range from determining the level of biodiversity in seawater samples to identifying cancerous cells in humans. Our work will focus on improving the sensitivity and reliability of low-power, fieldable devices and testing them on marine microorganisms. We are working with a harmless marine bacterium known as BBFL7, (Cytopaga-Flavobacteria-Bacteroidets group). The project involves Farooq Azam at the Scripps Institution of Oceanography, who provides the expertise in marine microbial ecology. The industrial partner for this effort is the Hitachi Chemical Research Center in Irvine, CA. For the past 2 years the UCSD group has been working in collaboration with Hitachi, and this project represents an expansion of that successful effort.

Researchers: Manuel Orosco, Francesca Malfatti (from SIO)



Anne Ruminski by the platform containing her submersible sensor for dissolved organics in seawater, prior to loading on ship. November, 2006. Photo: Glenn Sasagawa
Exploratory Research: Evaluation of Porous-Silicon Sensors for Marine Science Applications
NSF-Division of Ocean Sciences (NSF-OCE 0525080)
This project seeks to explore appplications in the ocean sciences for porous Si sensors. The current development effort concentrates on dissolved methane in seawater. The chemical balance of methane in seawater above methane fields, and its flux through the water column is a critical but poorly known quantity. This work will also provide the basis for assessing the potential of porous Si to detect other chemical and biological signals of interest to the ocean sciences. The effort represents a collaboration with Miriam Kastner and Glenn Sasagawa at the Scripps Institution of Oceanography.

Researchers: Anne Ruminski


Main address: Department of Chemistry, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA 92093-0358
Send questions, comments, and suggestions to: msailor@ucsd.edu.