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Nanotechnology – The Enabling Tool for the 21st Century Jackie Y. Ying Institute of Bioengineering and Nanotechnology Agency for Science, Technology and Research Singapore www.ibn.a-star.edu.sg Grand Challenges for the 21st Century 14 Grand Challenges in Engineering to Impact Sustainability, Health, Vulnerability, and Joy of Living www.engineeringchallenges.com National Academy of Engineering, U.S.A. • Engineering Better Medicine → Nanomedicine • Early Diagnosis of Diseases → Nanodevices • Sequestration of Green House Gases → Nanocatalysts • Making Solar Energy Economical → Nanomaterials Stimuli-Responsive Drug Delivery Systems Encapsulated substrate Encapsulated substrate Substrate release pH temperature time hydrolysis Polymer degradation Substrate release Hydrogel particle Conventional Release Mechanism • Constant or exponential release over time • Responsive to pH or temperature change Need for Stimuli-Responsive Drug Delivery • Insulin delivery to patients with diabetes mellitus – Insulin release in response to glucose concentration – Mimic physiological secretion – Eliminate the need for patient blood sugar monitoring Polymer swelling Stimuli-Responsive Drug Delivery Systems • Insulin delivery to patients with diabetes mellitus – Insulin release in response to glucose concentration – Mimic physiological secretion – Eliminate the need for patient blood sugar monitoring • Glucose-sensitive polymers – Tetravalent glucose-binding protein (e.g. Con A) – Polymer containing glucosyl groups (e.g. Dextran) 1. Free glucose diffuses into matrix 2. Free glucose competes with polymeric glucose 3. Crosslinking protein releases polymer chains 4. Matrix degrades allowing substrate release Tailoring of Insulin Delivery Nanoparticles Glucose-sensitive polymers as insulin carrier Protect insulin to enable oral or nasal delivery Degrade only at high blood glucose concentration Cumulative Insulin Release 120% Formulation of polymer as [glucose] (mg/dl) 400 nanoparticles 100% Small enough to escape macrophage 80% digestion 60% Enhance systemic absorption 100 and 40% 50 bioavailability 20% 0% 0 50 100 150 Time (min) Dextran 70K 200 nm 200 250 Cumulative Dex-Insulin Release Insulin released upon polymer degradation 120% [glucose] (mg/dl) 100% 400 80% 60% 40% 20% 50, 100 0% 0 50 100 150 Time Time(min) (min) Dextran-Insulin 200 250 MicroKit for Infectious Disease Diagnosis Challenge – Rapid, accurate diagnosis of infectious diseases (Market: $2.1B) Solution – A fully integrated, portable system: MicroKit • Disposable polymer cartridges with self-contained reagents • Automated sample processing → Rapid isolation of purified RNA and/or DNA from tissues and body fluids • Automated microfluidics and RT-PCR detection Impact – Early detection and subtyping of influenza (H1N1) and other viral infections in ~ 2 hours • Spinoff: SG Molecular Diagnostics • New platform for the simultaneous diagnosis of multiple samples for up to 25 diseases in 1 hour • Focus on diagnosis of bacterial infection → Critical in treatment of “superbugs” Lab on a Chip (2010) Carbon Dioxide Utilization and Conversion Challenge – 5500 MT/year of carbon emissions causing global warming Solution ‒ Utilize CO2 as a cheap, sustainable C1 feedstock Methanol CO CO2 R-C≡C-COOH R-C═C-COOH Green Energy: Methanol (Market: 70 MT/year) • Highly effective carbene organocatalyst N N → Ambient reaction with > 90% yield → Oxygen-tolerant, metal-free catalyst → Heterogeneous polycarbene catalyst allows for ease of recycling Green Synthesis of Pharmaceuticals and Chemicals • Propiolic acid, acrylic acid (US Market: 1.3 MT/year) Impact – Environmental protection against global warming – Green synthesis of chemicals Advanced Materials for Energy Applications Hollow PtRu Alloy Ru/Hollow Pt Bell-cage Pt-Ru CdSe@Pt Core-Shell Nat. Mater. (2009), J. Am. Chem. Soc. (2010) PbS–Au Nanocomposites of metals, semiconductors, oxides – Unique size effects and synergism between components – Unprecedented control of microstructures, morphologies → Materials with superb activity, selectivity, efficiency Clean, efficient energy conversion and storage • Fuel cells • Solar cells • Batteries PtFe–Au Nanonecklace