Nanotechnology – The Enabling Tool for the 21st Century

1. 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

2. 14 Grand Challenges in Engineering to Impact Sustainability, Health, Vulnerability, and Joy of Living • Engineering Better Medicine → Nanomedicine • Early Diagnosis of Diseases → Nanodevices • Sequestration of Green House Gases → Nanocatalysts • Making Solar Energy Economical → Nanomaterials Grand Challenges for the 21st Century www.engineeringchallenges.com National Academy of Engineering, U.S.A.

3. hydrolysis Stimuli-Responsive Drug Delivery Systems Encapsulated substrate Substrate release Encapsulated substrate Substrate release pH temperature time Polymer degradation Hydrogel particle Polymer swelling • 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

4. 1. Free glucose diffuses into matrix 3. Crosslinking protein releases polymer chains 2. Free glucose competes with polymeric glucose 4. Matrix degrades allowing substrate release 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)

5. 200 nm 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 Insulin released upon polymer degradation Formulation of polymer as nanoparticles Small enough to escape macrophage digestion Enhance systemic absorption and bioavailability 120% 120% [glucose] (mg/dl) [glucose] (mg/dl) 400 100% 100% 400 80% 80% 60% Cumulative Dex-Insulin Release 60% Cumulative Insulin Release 100 40% 40% 50 20% 20% 50, 100 0% 0% 0 50 100 150 200 250 0 50 100 150 200 250 Time (min) Time (min) Time (min) Dextran 70K Dextran-Insulin

6. 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)

7. Carbon Dioxide Utilization and Conversion Challenge– 5500 MT/year of carbon emissions causing global warming Solution‒ Utilize CO2 as a cheap, sustainable C1 feedstock Green Energy: Methanol (Market: 70 MT/year) • Highly effective carbene organocatalyst → 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 Methanol CO Reductants CO2 R-C≡C-COOH R-C═C-COOH R-C≡CH

8. Advanced Materials for Energy Applications Bell-cage Pt-Ru Hollow PtRu Alloy Ru/Hollow Pt 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