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RESEARCH SUMMARY: We synthesize nanomaterials and study their fundamental chemistry, photochemistry, electrochemistry, optical physics, and biomaterials properties. Our emphasis is on low toxicity or non toxic systems, with a particular emphasis on porous silicon. Research topics involve drug delivery materials, chemical and biochemical sensors, and in-vivo imaging with fluorescent or magnetic nanoparticles.

Current projects
Research highlights
Porous Si introduction and preparation
Equipment and schematics
Software links
Image gallery
Movies

Build your own humidity sensor (suitable for high school level)

"Etching 101" YouTube video on how to prepare porous silicon

Prof. Sailor's TEDx Talk on Nanotechnology: "The Three Laws of Nanorobotics"

Research Collaborators

Prof. Sailor's book "Porous Silicon in Practice" available from Wiley-VCH

Web resources for porous silicon

 


Current Projects

porous Si nanoparticles
Porous silicon nanoparticles. These particles, each 100 times smaller than a human hair, contain microscopic reservoirs that can hold and protect sensitive drugs. The surface of the particles can be covered with targeting molecules. When injected into the blood stream, the targeted nanoparticles seek out and then enter diseased cells, where they then release their therapeutic payloads. Photo Credit: Chia-Chen Wu, UCSD

Infection-homing nanosystems as antibacterial therapeutics-delivery platforms

Sponsor: NIH BIOENGINEERING RESEARCH GRANTS (BRG) (R01)

This project brings together a multi-disciplinary team of experts in basic research, translational investigation, and clinical medicine: Dr. Erkki Ruosalhti (Sanford-Burnham Medical Research Institute, SBMRI), Dr. Sangeeta N. Bhatia (MIT), and the Sailor lab at UCSD.

Staphylococcus aureus and Pseudomonas aeruginosa are the leading causes of hospital-acquired infections and contribute significantly to morbidity and mortality. Standard treatment of infection entails repetitive high-dose administrations of antibiotics, but the treatment is often rendered ineffective due to poor delivery to sites of infection and drug resistance mechanisms preventing antibiotic access to intracellular drug targets (e.g. the drug impermeable cell wall in gram-negative P. aeruginosa). Skin infections that have invaded down to the muscles and fibers are also difficult to reach by free-antibiotic formulations and require surgical treatment. The obstacles we tackle in this proposal are: (1) loss of antibiotics to non-infected tissues; (2) rapid clearance of small molecule antibiotics by renal and gastrointestinal clearance; (3) poor penetration of drugs past the bacterial cell wall. We hypothesize that loading antibiotics into longer-circulating nanovehicles that will home to sites of infection and subsequently facilitate drug uptake into cells/bacteria of interest can overcome the abovementioned challenges. This project will engineer two nanoplatforms: (1) peptide-based agents that can selectively penetrate the bacterial membrane (i.e. peptide permeation agents) to which small molecule drugs will be tethered for increased uptake and (2) porous silicon nanoparticles (pSiNP) to load drugs that have poor delivery to sites of infection due to unfavorable physicochemical properties (hydrophobic, highly ionic, etc). These nanoplatforms will be targeted to sites of infection using peptides we have previously discovered or additional peptides to be identified in the course of this research. Model drugs with poor in vivo antibacterial activity will be loaded and optimal platforms selected based on drug loading, release kinetics, and cellular uptake for in vivo pharmacokinetics. Finally, we will focus on the therapeutic performance of lead nanoplatform candidates in vivo. The goal is to demonstrate the biosafety and therapeutic efficacy (i.e. bacterial burden clearance, tissue recovery, improved survival) of the nanosystems.

Publications:
Kim, T.; Braun, G. B.; She, Z.-g.; Hussain, S.; Ruoslahti, E.; Sailor, M. J., Composite Porous Silicon-Silver Nanoparticles as Theranostic Antibacterial Agents. ACS Appl. Mat. Interfaces 2016, 8, 30449.

Researchers: Byungji Kim, Jinyoung Kang


Particles
Porous nanomaterials made from inorganic solids, polymers, or solid/polymer composites release drugs at very different rates. Commonly the rate of release of a drug in vitro does not match its performance in vivo. This project aims to develop tools to better predict in vivo performance from in vitro data. Photo Credit: Yangyang Li, UCSD

Modeling of the vitreous for in vitro prediction of drug delivery of porous silicon particles and episcleral plaques

Sponsor: FDA U01FD005173-01

This project aims to develop a simulator that accurately mimics the flow and biochemical conditions encountered in the vitreous environment, to provide a testbed system for in vitro evaluation of nanomaterial drug delivery systems.

Researchers: Joanna Wang



nanoparticle
Top: Luminescent porous silicon nanoparticles in a vial. The vial is being illuminated with an ultraviolet ("black") light, and the bright red-orange photoluminescence is observed. Bottom: TEM image of a porous Si nanoparticle embedded with iron oxide nanoparticles. Scale bar is 50 nm. Prepared from high-purity silicon wafers, these nanoparticles provide a non-toxic and biodegradable alternative to conventional quantum dots for drug delivery and medical diagnostic applications. Photo Credits: Luo Gu, Ji-Ho Park, Matt Kinsella, UCSD

Porous Silicon Nanoparticle/Polycaprolactone Composite Nanofibers for Nervous System Repair.

Sponsor: NSF-Division of Division of Chemical, Bioengineering, Environmental, and Transport Systems (CBET-1603177)

At present, there is no clinical treatment for spinal cord injury (SCI) that can completely restore lost function. Among the promising nerve regeneration strategies, nanofiber scaffolds are of intense interest. However, current nanofiber technologies lack the ability to fully repair the injured nervous system. This is in part due to the complex interplay of mechanical, biochemical, and biological factors associated with neuronal regrowth, and our limited understanding of this process. This project aims to develop and test biodegradable porous silicon nanoparticle/polymer composite nanofibers with the capability of providing the appropriate physical and chemical cues to regrowing neurons. In order to provide chemical cues that could be used to guide neuronal repair, we plan to incorporate drug-loaded porous silicon nanoparticles into nanofibers. It is difficult to incorporate sensitive therapeutics (such as proteins, siRNA, etc.) into nanofibers due to the volatile solvents that are used in their fabrication. Porous silicon nanoparticles can protect and deliver sensitive biological therapeutics, and they can be used to alter the degradation rate of nanofiber scaffolds. The project aims to develop next-generation nanofiber scaffolds as regenerative substrates to enhance the growth of extending neurites.

Publications:

Researchers: Jon Zuidema, Geoffrey Hollett


Microparticle disks of porous Si
Scanning electron microscope image of microfabricated porous silicon photonic crystal particles. The materials are used as in-vivo drug delivery materials. The particles contain a porous nanostructure that produces unique physical, chemical, and optical properties. The nanostructured nature of the material allows control of properties such as degradation rate, drug loading capacity, and temporal drug release profile. Photo credit: Shawn O. Meade, UCSD

Development of a Longer-Acting Injectable Contraceptive

Sponsor: FHI-360

More than one-third of contraceptive users in sub-Saharan Africa choose injectable contraceptives. Despite their popularity, discontinuation rates are high, and currently available formulations are effective for only 1 to 3 months, requiring women to return to their provider 4 to 12 times per year. FHI 360 is funding an exploratory project in our lab aimed at developing an injectable contraceptive that would last for 6 months. If successful, this project could expand contraceptive access and choice for women around the world. We are focusing on controllably biodegradable porous silicon (pSi) microparticlesas host matrices for contraceptive drugs such as progestins. The composite nanostructures are intended to act as a depot formulation that will degrade in vivo into non-toxic byproducts at a controllable rate, releasing the contraceptive payload at a therapeutic concentration for up to six months and then tapering quickly to allow a rapid return to fertility. The major challenge here is to engineer the nanomaterial to deliver drug at a constant rate for the duration of the therapy, and then disappear very quickly when the drug reservoir is exhausted.



Researchers: Geoffrey Hollett




pSi on Fiber
Fiber sensor
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 and Brian H. King.

End of Service Life Indicators in PAPR cartridges Using Carbonized Porous Si Photonic Crystals
Sponsor: NIOSH/NPPTL

This project is developing the basic science to enable chemical microsensors, with a specific focus on monitors for personal and collective protection equipment for breathable air. One targeted outcome of the work is small, low-power chemical detectors for volatile organic compounds (VOCs) suitable for insertion into activated carbon respirator cartridges as end-of-service-life (ESLI) or residual life (RLI) indicators. We have developed an extrinsic sensor for VOCs by adhering a 0.5 mm-diameter nanostructured porous silicon photonic crystal to an optical fiber. The approach relies on porous silicon-based photonic crystals modified such that they present a high surface area matrix with a high affinity for the indicated compounds. We have demonstrated their ability to act as chemical indicators for VOCs, explosives, and CW agents. When modified with a hydrophobic carbon-like porous matrix, the photonic crystals change color in the presence of a broad class of chemical agents and VOCs at sub-ppm concentrations, and are thus well suited as low-power indicators of chemicals in the respirator environment. The materials can be autonomously monitored with a low-power LED–based optical interrogation subsystem. The focus of the current work is to insert and test carbonized porous Si photonic crystal sensors in a PAPR (powered air purifying respirator) device. This project is a close collaboration with Dr. Jay Snyder at NIOSH

There is a growing need for sensors that can monitor the residual adsorption capacity of activated carbon filtration cartridges in gas masks and other personal protective equipment. Typically, these sensors operate by detecting organic vapors as they break through a filter bed of activated carbon. Despite advancements in end-of-service-life sensor technologies, the need persists for a very small, low-power, and cost-effective sensor. In the United States, government health and safety regulations require the detection of VOCs prior to depletion of the carbon bed’s adsorption capacity, yet these regulations have not yet been enforced due to a lack of suitable sensing devices. Fiber-optic-based sensors have been applied to a variety of remote sensing problems: measurement of pressure, humidity, vapor-phase chemicals, and aqueous biomolecules are leading examples. With a width of only a few tens to hundreds of microns, these sensors require little power to operate, are impervious to electrical interference, and can be multiplexed together into distributed sensor configurations. Fiber sensors may be extrinsic or intrinsic, depending on how the measured parameter is optically transduced; intrinsic sensors, like interferometric and Fabry-Perot cavity devices, leverage the fiber’s inherent optical properties to transform a parameter such as mechanical stress into an optical signal. Extrinsic sensors, such as bead-based arrays and polymer caps, immobilize an indicator or label on the distal end of the fiber, using only the light-carrying capability of the fiber to transduce the sensor signal. In this work, we have been developing an extrinsic sensor for volatile organic compounds (VOCs) by adhering a 0.5 mm-diameter porous Si photonic crystal to an optical fiber. The device has been inserted and tested in a PAPR (powered air purifying respirator) device.

The work has involved the development and demonstration of porous Si-based photonic chemical sensors as residual life indicators in adsorbent cartridges. The key enabling technologies we have developed for this application are (1) we discovered chemically sensitive, microporous photonic crystals that can be mounted on the distal end of an optical fiber. When inserted into an activated charcoal filter cartridge, the sensors detect breakthrough of organic vapors at the ppm level; (2) we have developed a chemical modification process that coats the inner pores of the photonic crystal with a high surface area carbon whose physicochemical properties mimic that of the activated carbon adsorbent bed. The modification increases sensitivity to volatile organic compounds by > 10x relative to the sensor we demonstrated in (1). The current goals of this project are to produce a microsensor prototype that can determine the VOC saturation level and residual life of activated charcoal filters.

Publications:
Chan, D. Y.; Sega, A. G.; Lee, J. Y.; Gao, T.; Cunin, F.; Renzo, F. D.; Sailor, M. J., "Optical detection of C2 hydrocarbons ethane, ethylene, and acetylene with a photonic crystal made from carbonized porous silicon." Inorg. Chim. Acta 2014, 422, 21–29.

Kelly, T. L.; Gao, T.; Sailor, M. J., "Carbon and Carbon/Silicon Composites Templated in Microporous Silicon Rugate Filters for the Adsorption and Detection of Organic Vapors." Adv. Mater. 2011, 23, 1776–1781.

Ruminski, A. M.; King, B. H.; Salonen, J.; Snyder, J. L.; Sailor, M. J., Porous silicon-based optical microsensors for volatile organic analytes: effect of surface chemistry on stability and specificity. Adv. Funct. Mater. 2010, 20, 2874–2883.

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.


Researchers:


Psi in eye
Porous Si microparticles injected into rabbit eye. Image credit: Dr. Lingyun Cheng, Jacobs Retina Center.

Porous Silicon Particles for Sustained Intravitreal Drug Delivery
Sponsor: NIH R01 EY020617-01A1
Whereas systemic administration (by IV injection) is the focus of much of our nanoparticle work, the objective of the microparticle-based drug delivery project is locallized injection into the target organs, such as the eye or peritonneal cavity. The micron-scale vehicles are based on nanostructured porous Si, and the approach involves infusion of a molecule into a chemically modified matrix of nanocrystalline porous Si or SiO2. Anti-inflammatory (dexamethasone), anti-proliferative (daunorubicin, doxorubicin), or antibiotic (vancomycin) drugs are being investigated with these microscopic particulate carriers. The larger sized porous Si microparticles allow the loading of much larger quantities of drug, appropriate for long-term (>4 month) therapies. We are developing chemistries to cap the pores with noble metals, polymers, proteins, and silica derived from silanols, 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.

Publications:
Hou, H.; Nieto, A.; Ma, F.; Freeman, W. R.; Sailor, M. J.; Cheng, L., Tunable sustained intravitreal drug delivery system for daunorubicin using oxidized porous silicon. J. Control Release 2014, 178, 46–54.

Nieto, A.; Hou, H.; Sailor, M. J.; Freeman, W. R.; Cheng, L., Ocular silicon distribution and clearance following intravitreal injection of porous silicon microparticles. Exp. Eye Res. 2013, 116, 161-168.

Hartmann, K. I.; Nieto, A.; Wu, E. C.; Freeman, W. R.; Kim, J. S.; Chhablani, J.; Sailor, M. J.; Cheng, L. Y., Hydrosilylated Porous Silicon Particles Function as an Intravitreal Drug Delivery System for Daunorubicin. J. Ocul. Pharmacol. Ther. 2013, 29 (5), 493-500.

Chhablani, J.; Nieto, A.; Hou, H.; Wu, E. C.; Freeman, W. R.; Sailor, M. J.; Cheng, L., Oxidized Porous Silicon Particles Covalently Grafted with Daunorubicin as a Sustained Intraocular Drug Delivery System. Invest Ophthalmol Vis Sci. 2013, 54, 1268–1279.

Wu, E. C.; Andrew, J. S.; Buyanin, A.; Kinsella, J. M.; Sailor, M. J., Suitability of porous silicon microparticles for the long-term delivery of redox-active therapeutics. Chem. Commun. 2011, 47, 5699–5701.

Researchers: Joanna Wang



Recently Completed Projects

pSi nanoparticles in dendritic cells
Porous Si nanoparticles in dendritic cells. Image stack representing a series of confocal fluorescence microscope images of mouse bone marrow-derived dendritic cells (BMDC) cultured with luminescent porous silicon nanoparticles containing attached FGK45 (FGK-LPSiNP). FGK45 is an antibody to mouse CD40. Red in the images corresponds to the near-IR (700 nm) emission from the nanoparticles and green is the 535 nm emission of Alexa Fluor 488 (conjugated to CD11c antibody to image the BMDCs). The confocal z-stack movie contains 12 frames covering a total depth of 10 microns; depth of a single frame is 0.82 micron. Image credit: Dr. Luo Gu, UCSD Chemistry and Biochemistry.

Micro RNAs for Therapy of Visual Disorders

Sponsor: NIH (R24 EY022025-01)

This research involves a collaboration between researchers at UCSD and TSRI. The goal is to develop a porous nanoparticle sustained delivery system that will sequester and release microRNA in a controlled fashion. A significant barrier to RNA therapies is the degradation of the oligonucleotide before it is able to reach its target. We hypothesize that porous silicon nanoparticles (PSiNP) will be able to carry and protect an anti-miR payload, and deliver it to tissues in its active form. The research crosses multiple disciplines and requires significant effort from three groups: there is a materials/chemistry component for development of the nanomaterials (Sailor), a biology component that will influence this development in vitro and in vivo (Cheresh), and a biomedical component (Friedlander) that will exploit our advances to push toward a clinical translation.

Publications:
Gu, L.; Ruff, L. E.; Qin, Z.; Corr, M.; Hedrick, S. M.; Sailor, M. J., "Multivalent Porous Silicon Nanoparticles Enhance the Immune Activation Potency of Agonistic CD40 Antibody". Adv. Mater. 2012, 24, 3981-3987.

Singh, N.; Karambelkar, A.; Gu, L.; Lin, K.; Miller, J. S.; Chen, C. S.; Sailor, M. J.; Bhatia, S. N., "Bioresponsive Mesoporous Silica Nanoparticles for Triggered Drug Release." J. Am. Chem. Soc. 2011, 133, 19582-19585.

Park, J.-H.; Gu, L.; Maltzahn, G. v.; Ruoslahti, E.; Bhatia, S. N.; Sailor, M. J., "Biodegradable luminescent porous silicon nanoparticles for in vivo applications." Nature Mater. 2009, 8, 331-336.

Researchers: Jinyoung Kang, B.J. Kim

porous Si nanoparticles
Porous silicon nanoparticles. These particles, each 100 times smaller than a human hair, contain microscopic reservoirs that can hold and protect sensitive drugs. The surface of the particles can be covered with targeting molecules. When injected into the blood stream, the targeted nanoparticles seek out and then enter diseased cells, where they then release their therapeutic payloads. Photo Credit: Chia-Chen Wu, UCSD

Porous Si-Based Therapeutic Nanoplatforms

Sponsor: DARPA in Vivo Nanoplatforms for Therapeutics (IVN:Tx) program (Cooperative Agreement HR0011-13-2-0017)

This project brought together a multi-disciplinary team of experts in basic research, translational investigation, and clinical medicine: Dr. Erkki Ruosalhti (Sanford-Burnham Medical Research Institute, SBMRI), Dr. Sangeeta N. Bhatia (MIT), and Joachim Spiess (SBMRI). The goal was to make readily reconfigurable modular nano-components developed in our lab and at MIT to effectively target and treat inflammation and infection, particularly those associated with traumatic brain injuries. The nanoparticles are targeted to infected or inflamed tissues using tissue-penetrating peptides developed by the SBMRI team using in vivo phage display.

A major contributor to the mortality associated with a penetrating brain injury is the elevated risk of intracranial infection. Under normal conditions, the blood-brain barrier acts as the brain’s internal defense against such infections. However, those same natural defense mechanisms make it difficult to get antibiotics to the brain once an infection has taken hold. Added to this problem is the emergence of bacteria that are highly resistant to current antibiotics. Our approach is focused on porous nanoparticles that contain highly effective therapeutics on the inside and targeting molecules on the outside. The targeting molecules also activate tissue-specific transport pathways to deliver the nano-therapeutics deep into the targeted tissues. Ruoslahti’s researchers at SBMRI have demonstrated specific targeting of tissues such as brain tumors, atherosclerotic plaques, and blood clots in the heart, and we are having similar success with diseases involving the brain. Because they mutate and evolve rapidly, drug-resistant bacterial strains are a particular challenge. In an attempt to hit this moving target, we use modular systems that can be reconfigured “on-the-fly” with the latest therapeutic advances. Sangeeta Bhatia, bioengineering professor at the Massachusetts Institute of Technology, has developed nanocomplexes that contain short interfering RNA, or siRNA. Both the MIT and the UCSD nanoparticles form a protective coating around siRNA, shielding the complex from nucleases and other metabolic processes in the body that would normally destroy the oligonucleotide.

More information

Publications:
Joo, J.; Cruz, J. F.; Vijayakumar, S.; Grondek, J.; Sailor, M. J., "Photoluminescent Porous Si/SiO2 Core/Shell Nanoparticles Prepared by Borate Oxidation." Adv. Funct. Mater. 2014, 24, 5688-5694.

Qin, Z.; Joo, J.; Gu, L.; Sailor, M. J., "Size Control of Porous Silicon Nanoparticles by Electrochemical Perforation Etching." Part. Part. Syst. Charact. 2014, 31, 252–256.

Gu, L.; Hall, D. J.; Qin, Z.; Anglin, E.; Joo, J.; Mooney, D. J.; Howell, S. B.; Sailor, M. J., "In vivo time-gated fluorescence imaging with biodegradable luminescent porous silicon nanoparticles." Nat. Commun. 2013, 4, 2326.

Researchers: Jinmyoung Joo, Jinyoung Kang, Dokyoung Kim, Taeho Kim, B.J. Kim

perforated etch
Porous, layered structure containing periodic strain releasing layers in silicon. Material prepared by "perforated" etch. Photo Credit: Zhengtao Qin, UCSD

Porous-Silicon-based Lithium Ion Anodes for Secondary Batteries

Sponsor: University of California Enabling Technology Development Contract No. 500-01-043

This project is in collaboration with Prof. Shirley Meng (UCSD Nanoengineering), PI Energy, inc., and the group led by Jason Zhang at PNNL. The objectives of this project are to optimize silicon etching conditions and carbonization chemistry needed to yield cycle life in excess of 3000 and capacity in excess of 1500 mAh/g

The pathway to commercially viable long-range electric vehicles (EVs) depends on high capacity electrochemical energy storage. Lithium-ion batteries (LIBs) are of special interest as power sources for EVs because of their high energy density and long lifetimes. Silicon has recently emerged as a promising candidate anode material, because it has one of the largest known theoretical specific capacities of 4200 milliampere-hours/gram, more than an order of magnitude larger than carbon-based materials currently used (theoretical maximum gravimetric capacity for lithium intercalation in graphite is 372 milliampere-hours/gram). However, the large volume expansion of Si upon Li intercalation leads to loss of mechanical integrity during the charge/discharge cycle, resulting in rapid capacity fade and loss of electric conductivity. To mitigate the effects of this volume change, the use of mesoporous silicon particles has been explored with some success. The objective of this project is to optimize the silicon etching conditions and carbonization chemistry to yield a manufacturable and scalable process that yields porous silicon-based anodes with cycle life in excess of 3000 and capacity in excess of 1500 milliampere-hours/gram. We aim to develop new chemistry to tailor the surface chemistry on porous silicon for optimal electrical conductivity and enhanced structural stability.

Publications:

Xiaolin Li, Meng Gu, Shenyang Hu, Rhiannon Kennard, Pengfei Yan, Xilin Chen, Chongmin Wang, Michael J. Sailor, Ji-Guang Zhang and Jun Liu, "Mesoporous Silicon Sponge as an Anti-Pulverization Structure for High-Performance Lithium-Ion Battery Anodes," Nature Communications, 2014, 5, 4105. DOI: 10.1038/ncomms5105. PRESS RELEASE: http://www.pnnl.gov/news/release.aspx?id=1059

Yersak, T. A.; Shin, J.; Wang, Z.; Estrada, D.; Whiteley, J.; Lee, S.-H.; Sailor, M. J.; Meng, Y. S., "Preparation of Mesoporous Si@PAN Electrodes for Li-Ion Batteries via the In-Situ Polymerization of PAN." ECS Electrochem. Lett. 2015, 4, A33-A36.

Researchers: Daniel Estrada, Rhiannon Kennard, David Roberts


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

Multifunctional Magnetic Nanoparticles for in vivo Imaging

Sponsor: 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 based on iron oxide (and more recently, manganese oxide and bismuth sulfide) that exploit biological processes to guide the targeting and accumulation of these materials to image 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.

Our group invented a new synthesis of iron oxide nanoparticles that results in a worm-like morphology. In collaboration with Erkki Ruoslahti’s group at the Burnham Institute and Sangeeta Bhatia’s lab at MIT, we placed short peptide moieties on these nanoworms that demonstrated effective targeting to tumors and other tissues. We found that the nano-worms circulate in mice for > 24 hours—longer than any of the commercially available or previously published iron oxide nanoparticle systems. Because of their significantly improved ability to circulate in the body and the higher contrast they display in MRI images relative to conventional iron oxide nanoparticles, this nanoworm synthesis has been duplicated and used by many other researchers for in-vivo imaging of tumors and for delivery of various therapeutics. Our 2008 Advanced Materials paper describing this work was selected by the editors as the "Best work published in Advanced Materials in 2008" based on feedback from reviewers, citations, and the number of full-text downloads.

Publications:
Kinsella, J. M.; Jimenez, R. E.; Karmali, P. P.; Rush, A. M.; Kotamraju, V. R.; Gianneschi, N. C.; Ruoslahti, E.; Stupack, D.; Sailor, M. J., "X-Ray Computed Tomography Imaging of Breast Cancer by using Targeted Peptide-Labeled Bismuth Sulfide Nanoparticles." Angew. Chem. Int. Ed. 2011, 50, 12308–12311.

Kinsella, J. M.; Ananda, S.; Andrew, J. S.; Grondek, J. F.; Chien, M.-P.; Scadeng, M.; Gianneschi, N. C.; Ruoslahti, E.; Sailor, M. J., "Enhanced Magnetic Resonance Contrast of Fe3O4 Nanoparticles Trapped in a Porous Silicon Nanoparticle Host." Adv. Mater. 2011, 23, H248–H253.

Maltzahn, G. v.; Park, J.-H.; Lin, K. Y.; Singh, N.; Schwöppe, C.; Mesters, R.; Berdel, W. E.; Ruoslahti, E.; Sailor, M. J.; Bhatia, S. N., "Nanoparticles that communicate in vivo to amplify tumour targeting." Nature Mater. 2011, 10, 545–552.

Park, J.-H.; Maltzahn, G. v.; Zhang, L.; Derfus, A. M.; Simberg, D.; Harris, T. J.; Bhatia, S. N.; Ruoslahti, E.; Sailor, M. J., "Systematic Surface Engineering of Magnetic Nanoworms for in vivo Tumor Targeting." Small 2009, 5, (6), 694-700.

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.



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

Separating, Processing, and Detecting Biomolecules in Silicon-Based Optical Nanostructures: Multifunctional Biosensors
Sponsor: NSF-Division of Materials Research (NSF DMR 0806859)

There is a major unmet need for microsensor technologies that can provide rapid and reliable identification and quantification of biological species in air, water, and patient samples. The objective of this project is to develop the fundamental materials science and chemistries needed to enable label-free biosensors that have the ability to perform separation, identification and quantification of key properties of biomolecules at low concentrations. We aim to develop new, unprecendented levels of selectivity and discrimination in optical biosensors by exploiting molecular transport through chemically functionalized and physically engineered porous Si matrices.  A key innovation of the present proposal that is not represented in the vast majority of existing optical biosensor work is that the sensor is the same physical entity that is performing analyte separation and isolation.  We refer to this approach as “signal processing at the materials level,” and we believe it is an important theme for the general area of functional nano materials.

Publications:
Chen, M. Y.; Sailor, M. J., "Charge-Gated Transport of Proteins in Nanostructured Optical Films of Mesoporous Silica". Anal. Chem. 2011, 83, 7186-7193.

Chen, M. Y.; Klunk, M. D.; Diep, V. M.; Sailor, M. J., "Electric Field Assisted Protein Transport, Capture, and Interferometric Sensing in Carbonized Porous Silicon Films." Adv. Mater. 2011, 23, 4537–4542.

Meade, S. O.; Chen, M. Y.; Sailor, M. J.; Miskelly, G. M., "Multiplexed DNA Detection Using Spectrally Encoded Porous SiO2 Photonic Crystal Particles." Anal. Chem. 2009, 81, 2618.



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.

Smart Dust: Manipulation of Chemicals, Biochemicals, and Cells with Porous Si Chaperones
Sponsor: NSF-Division of Materials Research (NSF DMR 0806859)
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.

Publications:
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

Thomas, J. C., Pacholski, C. & Sailor, M. J. "Delivery of Nanogram Payloads Using Magnetic Porous Silicon Microcarriers." Lab Chip 2006, 6, 782 - 787.

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.


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
Sponsor: NSF-Division of Materials Research (NSF DMR-0806859)
The goal of this project is to construct encoded particles that act as robust, non-toxic optical 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 developed these materials for various applications in high throughput screening and encoded bead-based assays. The use of these materials as non-toxic tags has been transitioned to TruTags, inc. (who markets the invention under the TruTag trademark) and to Minus9 Labs (who markets the invention unter the MINTs trademark).

Publications:
Sailor, M. J.; Meade, S. O. "Method for forming optically encoded thin films and particles with grey scale spectra." U.S. Patent #8,308,066, issued November 13, 2012.

Meade, S. O.; Chen, M. Y.; Sailor, M. J.; Miskelly, G. M.,"Multiplexed DNA Detection Using Spectrally Encoded Porous SiO2 Photonic Crystal Particles." Anal. Chem. 2009, 81 (7), 2618-2625.

Meade, S. O.; Sailor, M. J., "Microfabrication of freestanding porous silicon particles containing spectral barcodes." phys. stat. sol. (RRL) 2007, 1, (2), R71–R73.

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.

   

Although the scope of our work at the University is limited to basic research into the fundamental properties of materials, many of the concepts developed in our labs have been translated to products and processes in the commercial world. Any commercial products and processes that emerge from our fundamental discoveries are outside the course and scope of our University-related employment; however, we actively encourage transition of technologies to the commercial sector with the assistance of UCSD’s technology transfer office.


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.