IBN INSTITUTE OF BIOENGINEERING AND NANOTECHNOLOGY

Transcription

1 IBN INSTITUTE OF BIOENGINEERING AND NANOTECHNOLOGY

2 MISSION Provide international leadership in establishing a broad knowledge base in bioengineering and nanotechnology Conduct innovative research and create intellectual properties in these emerging fields, attracting top-notch researchers and business partners to Singapore Play an active role in technology transfer and spinning off small companies, linking the research institute and industrial partners to other global institutions Foster an exciting, multidisciplinary research environment for the training of students and young researchers at the frontiers of bioengineering and nanotechnology

3 CHARTING NEW FRONTIERS IN SCIENCE, ENGINEERING AND MEDICINE Since 2003, IBN has carved out a unique niche at the interface of bioengineering and nanotechnology. Led by Executive Director Professor Jackie Y. Ying, the Institute has conducted interdisciplinary research bridging science, engineering and medicine. IBN has focused on generating new knowledge and creating innovative technology platforms that combine novel catalytic chemistry, biomaterials, nanofabricated devices, and microfluidic systems with biological and biomedical engineering.

4 CHARTING NEW FRONTIERS IN SCIENCE, ENGINEERING AND MEDICINE INTERDISCIPLINARY RESEARCH IBN s strength in synthetic capability for chemicals, materials and biologics are targeted towards developing unique solutions to complex problems in four important areas. DRUG AND GENE DELIVERY CELL AND TISSUE ENGINEERING BIOSENSORS AND BIODEVICES where the controlled release of therapeutics involves the use of functionalized polymers, hydrogels and biologics for targeting diseased cells and organs, and for responding to specific biological stimuli. where biomimicking materials, stem cell technology, microfluidic systems, and bioimaging tools are combined to develop novel approaches to regenerative medicine and artificial organs. which involve nanotechnology and microfabricated platforms for high-throughput biomarkers screening, automated biologics synthesis, and rapid disease diagnosis. Human neurons transduced with baculoviral vectors harbor a green fluorescence gene. Human proximal tubule cells proliferating on IBN s new membrane biomaterial. All-in-one droplet-based device for rapid avian flu detection. PHARMACEUTICALS SYNTHESIS AND NANOBIOTECHNOLOGY which encompass the efficient catalytic synthesis of chiral pharmaceuticals, and new nanocomposite materials for sustainable technology and alternative energy generation. Microparticles of N-heterocyclic carbene as novel heterogeneous catalysts. Through interdisciplinary research, IBN scientists have tailored advanced materials and devices with novel functionalities in length scales of relevance to biological systems. As of June 2009, IBN has published 502 publications in leading journals. The research efforts have also led to an impressive technology portfolio of 714 patent applications. IBN Brochure 1 General Pg 2 & 3

5 CHARTING NEW FRONTIERS IN SCIENCE, ENGINEERING AND MEDICINE INTERDISCIPLINARY RESEARCH IBN s strength in synthetic capability for chemicals, materials and biologics are targeted towards developing unique solutions to complex problems in four important areas. DRUG AND GENE DELIVERY CELL AND TISSUE ENGINEERING BIOSENSORS AND BIODEVICES where the controlled release of therapeutics involves the use of functionalized polymers, hydrogels and biologics for targeting diseased cells and organs, and for responding to specific biological stimuli. where biomimicking materials, stem cell technology, microfluidic systems, and bioimaging tools are combined to develop novel approaches to regenerative medicine and artificial organs. which involve nanotechnology and microfabricated platforms for high-throughput biomarkers screening, automated biologics synthesis, and rapid disease diagnosis. Human neurons transduced with baculoviral vectors harbor a green fluorescence gene. Human proximal tubule cells proliferating on IBN s new membrane biomaterial. All-in-one droplet-based device for rapid avian flu detection. PHARMACEUTICALS SYNTHESIS AND NANOBIOTECHNOLOGY which encompass the efficient catalytic synthesis of chiral pharmaceuticals, and new nanocomposite materials for sustainable technology and alternative energy generation. Microparticles of N-heterocyclic carbene as novel heterogeneous catalysts. Through interdisciplinary research, IBN scientists have tailored advanced materials and devices with novel functionalities in length scales of relevance to biological systems. As of June 2009, IBN has published 502 publications in leading journals. The research efforts have also led to an impressive technology portfolio of 714 patent applications. IBN Brochure 1 General Pg 2 & 3

6 CHARTING NEW FRONTIERS IN SCIENCE, ENGINEERING AND MEDICINE INTERNATIONAL TALENT IBN brings together world-class talents from different disciplines to work in exciting new areas that would make a significant impact on society. Its multinational research talents are recruited from leading institutions in Australia, China, France, Germany, Hong Kong, India, Indonesia, Japan, Korea, Malaysia, Netherlands, Romania, Singapore, Sweden, Taiwan, Thailand, the United Kingdom and the United States of America. Their diverse expertise encompass biological, chemical, electrical and mechanical engineering, biology, chemistry, physics, materials sciences, computer science, pharmacy, and medicine. These highly motivated individuals share a common passion for improving the quality of life through new knowledge and technologies. IBN s commitment to nurturing young scientists and engineers is also evident in its Youth Research Program, which was established in October 2003 to introduce students and teachers from primary schools to tertiary institutions to bioengineering and nanotechnology research. As of June 30, 2009, the Youth Research Program has reached out to over 31,075 students and teachers from 205 schools and institutions through open houses, career talks, workshops and research attachments. More than 1,097 students and teachers have participated in full-time research attachments of at least one month at IBN.

7 WW.IBN.A-STAR. DU.SG

8 Institute of Bioengineering and Nanotechnology

9 IBN INSTITUTE OF BIOENGINEERING AND NANOTECHNOLOGY

10 IBN scientists are revolutionizing medical treatment with sophisticated biomaterials and systems for delivering therapeutics to diseased cells and organs.

11 DRUG AND GENE DELIVERY At IBN, researchers are combating chronic and degenerative diseases using next-generation materials to deliver drugs, genes, proteins and other biological agents to affected sites. Tailored to respond to specific physiological stimuli, these novel nanostructures provide greater control over the administration of therapeutics, thus enabling more targeted and effective treatment of cancer, fibrosis, brain and aging-related diseases.

12 DRUG AND GENE DELIVERY INSECT VIRUS FOR STEM CELL ENGINEERING The first successful gene delivery to human embryonic stem cells using an engineered insect virus was achieved at IBN. This breakthrough allows stem cells to be modified into other cell types for regenerative medicine and developmental biology research. Safer and more efficient than other delivery vehicles, IBN s engineered baculovirus can also transport large or multiple genes to treat a wide range of diseases such as neurological disorders and brain cancer. - J. Zeng, J. Du, N. Palanisamy and S. Wang, Stem Cells, 25 (2007) COVER: Engineered baculovirus for genetic modification of stem cells. We are interested in delivering therapeutic DNAs and gene-modified stem cells to brain tumors. Their combined use allows us to overcome key limitations of current treatments. DR SHU WANG GROUP LEADER NANOCARRIERS COMBAT MULTIDRUG-RESISTANT CANCER Biodegradable nanoparticles developed at IBN can deliver drugs and genes or proteins simultaneously to cancer cells, paving the way for more effective therapy of multidrug-resistant cancer. Bypassing healthy cells to release medication directly at tumor sites, they minimize side effects and enhance treatment efficacy. Antimicrobial agents with controlled molecular structures have also been engineered. These display a broad spectrum of antimicrobial activities against gram-positive bacteria, yeast and fungi, and kill multidrug-resistant microbes. - Y. Wang, S. J. Gao, H. Wen, H. S. Yoon and Y. Y. Yang, Nature Materials, 5 (2006) L. Liu, K. Xu, H. Wang, J. P. K. Tan, W. Fan, S. S. Venkatraman, L. Li and Y. Yang, Nature Nanotechnology, (2009) DOI: /NNANO We are designing new biomaterials to synthesize nanostructures for transporting drugs, proteins, genes and macromolecular antimicrobial agents to kill cancer cells or bacteria. DR YIYAN YANG GROUP LEADER Novel carriers co-deliver drugs and genes or proteins to treat multidrug-resistant tumors.

13 INJECTABLE HYDROGEL FOR DRUG DELIVERY AND TISSUE REGENERATION We are able to control the mechanical strength of our injectable hydrogel without affecting its gelation rate. DR MOTOICHI KURISAWA TEAM LEADER AND PRINCIPAL RESEARCH SCIENTIST New bone mineral deposits observed 4 weeks after administration of injectable bone cement. IBN s injectable hydrogel system is synthesized without toxic chemicals, allowing therapeutic proteins, growth factors and cells to be incorporated into the gel without being damaged. Besides regulating the rates of degradation, drug release, cell proliferation and differentiation, this novel hydrogel also prevents uncontrolled leakage of bioactive agents. As the biodegradable system does not cause inflammatory response in the body, it has tremendous potential for drug delivery and tissue regeneration applications. - M. Kurisawa, J. E. Chung, Y. Y. Yang, S. J. Gao and H. Uyama, Chemical Communications, (2005) Y. S. Pek, M. Kurisawa, S. J. Gao, J. E. Chung and J. Y. Ying, Biomaterials, 30 (2008)

14 DRUG AND GENE DELIVERY NEW NANOMATERIALS FOR EYE THERAPY A new class of nanostructured polymeric lens material has been synthesized at IBN using a patented method. This novel technique allows significant amounts of medication such as anti-glaucoma drugs to be loaded into the lens without affecting its mechanical strength or transparency. Modifying the nanochannels within the matrix and the drug concentration regulates the rate of drug release. Other innovations include ophthalmic devices and prostheses to treat various eye disorders. The nanopores in our lens material regulate the sustained release of the embedded therapeutics, thus increasing ocular bioavailability and minimizing adverse effects. DR EDWIN CHOW TEAM LEADER AND SENIOR RESEARCH SCIENTIST Drug-loaded contact lenses offer more effective treatment of eye diseases.

15 IBN DRUG AND GENE DELIVERY GROUP AND TEAM LEADERS DR SHU WANG GROUP LEADER Postdoctoral Fellow Umeå University, Harvard Medical School and University of California, San Francisco Ph.D. in Cell Biology/Neurobiology, Gothenburg University DR YIYAN YANG GROUP LEADER Ph.D. in Chemical Engineering, Tsinghua University DR MOTOICHI KURISAWA TEAM LEADER AND PRINCIPAL RESEARCH SCIENTIST Postdoctoral Fellow, Kyoto University Ph.D. in Materials Science, Japan Advanced Institute of Science and Technology DR EDWIN PEI YONG CHOW TEAM LEADER AND SENIOR RESEARCH SCIENTIST Ph.D. in Chemistry, National University of Singapore WW.IBN.A-STAR.

16 Institute of Bioengineering and Nanotechnology

17 IBN INSTITUTE OF BIOENGINEERING AND NANOTECHNOLOGY

18 At IBN, researchers are inventing new approaches to regenerative medicine using biomimicking materials, stem cell technology, microfluidic systems, and bioimaging tools.

19 CELL AND TISSUE ENGINEERING IBN scientists are designing advanced bioartificial organ assist devices and regenerative therapies for the treatment of liver, kidney, pancreatic and heart diseases. They are developing new nanostructured materials and bioreactor microdevices for cell and tissue engineering to help fight organ failures and degenerative diseases.

20 CELL AND TISSUE ENGINEERING QUANTUM DOTS AND MULTIFUNCTIONAL NANOCOMPOSITES We have synthesized buffer-stable, glutathione -capped quantum dots with excellent quantum yield via low-temperature aqueous synthesis. The glutathione coating is crosslinked to improve the nanoparticles stability and cell viability. PROF JACKIE Y. YING EXECUTIVE DIRECTOR AND SENIOR GROUP LEADER A one-step technique of synthesizing water-soluble quantum dots was developed at IBN. Coated with a natural peptide, these nanocrystals have narrow, tunable emission bands, higher photostability than organic dyes, high stability in biological systems and good biocompatibility. Novel nanocomposites of quantum dots and magnetic nanoparticles have also been derived, which allow for simultaneous bioimaging, biolabeling and cell separation. - D. K. Yi, S. T. Selvan, S. S. Lee, G. C. Papaefthymiou, D. Kundaliya and J. Y. Ying, Journal of the American Chemical Society,127 (2005) Y. Zheng, S. Gao and J. Y. Ying, Advanced Materials, 19 (2007) Y. Zheng, Z. Yang and J. Y. Ying, Advanced Materials, 19 (2007) S. T. Selvan, P. K. Patra, C. Y. Ang and J. Y. Ying, Angewandte Chemie International Edition, 46 (2007) J. Yang and J. Y. Ying, Nature Materials, (2009) DOI: /NMAT2490. COVER: Cell labeling using glutathione-coated quantum dots. BIOCOMPATIBLE ORTHOPEDIC IMPLANTS Conventional bone grafts or synthetic implants involve the risk of infection and lack biocompatibility. IBN s porous collagen-apatite bone scaffolds are structurally and chemically similar to natural bone, and highly bioactive with tunable mechanical properties and degradation rates. In vivo implantation showed bone, tissue and blood vessel formation in the scaffold material. The nanocomposite scaffold successfully healed bone defects in rats and pigs and restored functioning of the affected area without an external supporting cast. - Y. S. Pek, S. Gao, M. S. Mohamed Arshad, K.-J. Leck and J. Y. Ying, Biomaterials, 29 (2008) Sponge-like bone implants to treat fractures and orthopedic defects.

21 REVERSIBLE GEL FOR 3D CELL CULTURE IBN s thixotropic gel can be liquefied when sheared. IBN s thixotropic gel provides an effective and convenient platform for 3D cell culture. Unlike conventional cultures on flat surfaces, IBN s reversible gel mimics natural body conditions better, and cells can be transferred easily without using trypsin, which is known to compromise long-term cell quality. New methods have also been developed to provide the cultured cells with various biochemical and mechanical signals, thus facilitating new discoveries on cell behavior in 3D. - Y. S. Pek, A. C. A. Wan, A. Shekaran, L. Zhuo and J. Y. Ying, Nature Nanotechnology, 3 (2008) FIBROUS SCAFFOLDS FOR TISSUE ENGINEERING Porous fibers with ECM growth factors for tissue engineering. Unlike existing processes for producing tissue engineering scaffolds, IBN s interfacial polyelectrolyte complexation technique of forming scaffolds from fibers at room temperature is mild and aqueous-based. The porous fibers may be imbued with natural features of extracellular matrix, growth factors and peptide ligands to promote adhesion and differentiation of human mesenchymal stem cells, regulate cell behavior and support tissue growth. Potential applications include treatment of liver failure and Type I diabetes. - A. C. A. Wan, B. C. U. Tai, K.-J. Leck and J. Y. Ying, Advanced Materials, 18 (2006) We are now working to mimic the natural cell environment so as to develop in vitro 3D models for tissue engineering. DR ANDREW WAN TEAM LEADER AND PRINCIPAL RESEARCH SCIENTIST PERFUSION BIOREACTOR TO TREAT LIVER FAILURE We have developed enabling technologies to understand and engineer cell and tissue microenvironments. These are applied to fabricate innovative drug testing platforms and therapeutic solutions with enhanced performances. PROF HANRY YU GROUP LEADER Bioartificial liver assist devices promise more effective therapy for liver disease patients. However, many existing devices cause cell functions to decline rapidly due to poor maintenance of their microenvironment and inadequate removal of accumulated toxic metabolites. In contrast, IBN s perfusion liver bioreactor ensures long-term cell viability and functionality through the optimal supply of nutrients and gases. It also enables the removal and exchange of metabolites from the cell culture surfaces. - S. F. Zhang, X. Lei, S. M. Ong, Y. C. Toh, H. L. Leo, D. van Noort and H. Yu, Biomaterials, 29 (2008)

22 CELL AND TISSUE ENGINEERING NOVEL THERAPIES TO COMBAT LIVER DISEASE During liver injury, hepatic stellate cells produce excessive extracellular matrix protein, resulting in scarring and fibrosis. IBN scientists are targeting these cells with a particular GFAP promoter to develop an effective anti-fibrotic therapy. In vitro and in vivo fibrosis models are used to test novel compounds developed at IBN for their anti-fibrotic potential. Further investigations will be conducted in hepatocellular carcinoma research to develop effective treatments for liver disease patients. - L. Zhao, C. Zhang, L. Zhuo, Y. Zhang and J. Y. Ying, Journal of the American Chemical Society, 130 (2008) We have achieved specific targeting of hepatic stellate cells in vitro and in vivo. This breakthrough is particularly useful for the treatment of liver fibrosis. DR LANG ZHUO TEAM LEADER AND PRINCIPAL RESEARCH SCIENTIST EFFICIENT DIALYSIS WITH A PORTABLE RENAL ASSIST DEVICE Hemodialysis machines are bulky, require large volumes of dialysis fluids, and remove nutrients along with toxins from the patient s blood. IBN s bioartificial kidney incorporates a layer of kidney cells within specially designed membranes and hollow fibers. A semi-permeable membrane removes metabolic wastes but retains blood cells and larger proteins, while the kidney cells reabsorb nutrients into the patient s blood. - H. Zhang, F. Tasnim, J. Y. Ying and D. Zink, Biomaterials, 30 (2009) M. Hu, M. Kurisawa, R. Deng, C. M. Teo, A. Schumacher, Y. X. Thong, L. Wang, K. M. Schumacher and J. Y. Ying, Biomaterials, 30 (2009) Bioartificial kidneys would help to decrease the mortality rate of patients with acute renal failure. We are working to better understand and improve cell performance in such devices. DR DANIELE ZINK TEAM LEADER AND PRINCIPAL RESEARCH SCIENTIST Bioartificial kidney device allows re-absorption of nutrients in blood.

23 IBN CELL AND TISSUE ENGINEERING GROUP AND TEAM LEADERS PROF JACKIE Y. YING EXECUTIVE DIRECTOR AND SENIOR GROUP LEADER Postdoctoral Fellow, Institute for New Materials, Germany Ph.D. in Chemical Engineering, Princeton University PROF HANRY YU GROUP LEADER Postdoctoral Fellow, European Molecular Biology Laboratory Heidelberg and Duke University Medical Center Ph.D. in Cell Biology, Duke University DR ANDREW CHWEE AUN WAN TEAM LEADER AND PRINCIPAL RESEARCH SCIENTIST Postdoctoral Fellow, Johns Hopkins University Ph.D. in Chemistry, National University of Singapore DR LANG ZHUO TEAM LEADER AND PRINCIPAL RESEARCH SCIENTIST Postdoctoral Fellow, Waisman Center, University of Wisconsin Ph.D. in Molecular Biology, University of Wisconsin DR DANIELE ZINK TEAM LEADER AND PRINCIPAL RESEARCH SCIENTIST Postdoctoral Fellow, Institute of Human Genetics, University of Heidelberg Ph.D. in Natural Sciences, University of Heidelberg WW.IBN.A-STAR.

24 Institute of Bioengineering and Nanotechnology

25 IBN INSTITUTE OF BIOENGINEERING AND NANOTECHNOLOGY

26 Researchers at IBN use nanotechnology and microelectromechanical systems (MEMS) to fabricate miniaturized platforms for molecular sensing and disease diagnostics.

27 BIOSENSORS AND BIODEVICES IBN is transforming medical therapy and preventive healthcare through miniaturized devices that are able to detect diseases accurately at an earlier stage. New tools are also being developed for gene and protein synthesis, and biomarker screening and validation.

28 BIOSENSORS AND BIODEVICES EARLY DISEASE DETECTION WITH AUTOMATED BIOSAMPLE PREPARATION Our MEMS systems greatly facilitate the processing and preparation of biological samples for research and clinical applications. They are integrated with sensors for early diagnosis of cancer and infectious diseases. PROF JACKIE Y. YING EXECUTIVE DIRECTOR AND SENIOR GROUP LEADER Automated lab-on-a-chip system extracts and detects pure mrna from tissue in less than an hour to perform molecular diagnosis of cancer and infectious diseases. IBN s MicroKit is the first lab-on-a-chip that can extract and detect pure mrna from tissue or body fluid samples within an hour. It may be used at clinics and points-of-care to detect cancer, avian flu, hepatitis and other infectious diseases. The self-contained system minimizes risks from human error, sample exposure, contamination and degradation. Dyamed Biotech, which has licensed MicroKit, has spun-off SG Molecular Diagnostics to develop rapid and accurate diagnostic kits. NUCLEIC ACID BIOSENSORS TO DETECT CANCER MARKERS Unlike fluorescence technologies such as PCR-based microarrays, IBN s electrochemical biosensors detect nucleic acids without using complex and costly instrumentation. Electrochemical technology offers a simple reaction workflow and a user-friendly assay design process, allowing simple and rapid development of single or multiplexed diagnosis. These biosensors are currently being integrated with IBN s MicroKit to create a fully automated molecular diagnostic system. - H. Xie, C. Y. Zhang and Z. Q. Gao, Analytical Chemistry, 76 (2004) We are integrating nanostructured materials and biomaterials with electronic transducers for protein and nucleic acid detection, microfabrication, nanostructure self-assembly, microfluidic devices and nanoparticle-based bioassays. DR ZHIQIANG GAO GROUP LEADER

29 LAB-IN-A-DROPLET FOR DISEASE DIAGNOSIS Magnetic nanoparticles perform sample preparation and gene detection in a droplet. IBN s Virtual Reaction Chamber uses magnetism to manipulate a droplet successively through nucleic acid purification and preconcentration, followed by gene detection. This device is as sensitive as and radically faster than available tests, yet it could potentially be produced much more cheaply. The single-use system can also be easily adapted to a diverse range of PCR-based applications for research, diagnostics and industrial use. This technology has been licensed to MP Biomedicals. - L. Novak, P. Neuzil, J. Pipper, Y. Zhang and S. H. Lee, Lab on a Chip, 7 (2007) J. Pipper, M. Inoue, L. F.-P. Ng, Y. Zhang, P. Neuzil and L. Novak, Nature Medicine, 13 (2007) J. Pipper, Y. Zhang, P. Neuzil and T. M. Hsieh, Angewandte Chemie, 47 (2008) We have integrated a microfluidic platform with multiplexed optical sensors to create a hand-held unit for decentralized tests targeting infectious diseases, forensics and genotyping. DR FRANCIS ENG HOCK TAY GROUP LEADER AUTOMATED SYNTHESIS OF ARTIFICIAL DNA We have developed a fully integrated gene synthesis platform that can synthesize a 10 kbp DNA sequence directly from raw chemicals at low cost and fast turnaround. DR MO-HUANG LI TEAM LEADER AND SENIOR RESEARCH SCIENTIST An automated gene synthesis platform comprising proprietary bioinformatics software, a high-throughput oligonucleotide synthesizer and novel techniques for increasing the yield and purity of the synthesized genes has been developed at IBN. The synthetic genes with biological functions can be used in various applications such as synthetic genome development, protein overexpression, as well as protein and vaccine engineering.

30 BIOSENSORS AND BIODEVICES WATER-BASED SMELL RECEPTORS FOR DEVELOPING ULTRASENSITIVE SENSING DEVICES G-protein coupled receptors (GPCRs) belong to one of the most important protein classes in higher living systems. They are directly involved in sensing, learning, memory, and numerous other brain functions. Smell is one of the most primitive and fundamental senses. The laboratory for Membrane Protein Nanobiotechnology is focused on the study of water-based smell receptors to gain detailed structural knowledge to design ultrasensitive devices for very early non-invasive, simple and quick medical diagnosis. Research on water-based receptors will enable us to integrate emerging synthetic biology and membrane protein nanobiotechnology to develop novel platforms for biosensing and drug screening. DR CHARLOTTE HAUSER TEAM LEADER AND PRINCIPAL RESEARCH SCIENTIST DR SHUGUANG ZHANG VISITING INSTITUTE FELLOW MINIATURIZED ASSAYS FOR FASTER DRUG SCREENING IBN s DropArray performs cell-based tests, including cancer stem cell immunoassays, much more cheaply and faster than conventional technologies. Each chip comprises hundreds of tiny glass wells that act as miniaturized test tubes to which reagents are added, mixed and incubated. An automated bench-top system performs the rinsing processes required. German-listed Nanostart AG has invested in this technology and IBN s first spin-off company, Curiox Biosystems, has been incorporated to market this technology. IBN s spin-off Curiox Biosystems Pte Ltd is commercializing droplet microarrays for miniaturized bioassays.

31 IBN BIOSENSORS AND BIODEVICES GROUP AND TEAM LEADERS PROF JACKIE Y. YING EXECUTIVE DIRECTOR AND SENIOR GROUP LEADER Postdoctoral Fellow, Institute for New Materials, Germany Ph.D. in Chemical Engineering, Princeton University DR SHUGUANG ZHANG VISITING INSTITUTE FELLOW Associate Director, Center for Biomedical Engineering, Massachusetts Institute of Technology Postdoctoral Fellow, Massachusetts Institute of Technology Ph.D. in Biochemistry and Molecular Biology, University of California, Santa Barbara DR ZHIQIANG GAO GROUP LEADER Postdoctoral Fellow, Abo Akademi University and Weizmann Institute of Science Ph.D. in Chemistry, Wuhan University DR FRANCIS ENG HOCK TAY GROUP LEADER Ph.D. in Mechanical Engineering, Massachusetts Institute of Technology DR CHARLOTTE HAUSER TEAM LEADER AND PRINCIPAL RESEARCH SCIENTIST Postdoctoral Fellow, Massachusetts Institute of Technology and Institut National de la Santé et de la Recherche Médicale Ph.D. in Molecular Biology, Massachusetts Institute of Technology and University of Cologne DR MO-HUANG LI TEAM LEADER AND SENIOR RESEARCH SCIENTIST Postdoctoral Fellow, University of Wisconsin-Madison Ph.D. in Electrical and Computer Engineering, University of Wisconsin-Madison WW.IBN.A-STAR.

32 Institute of Bioengineering and Nanotechnology

33 IBN INSTITUTE OF BIOENGINEERING AND NANOTECHNOLOGY

34 A key research focus at IBN is the development of novel catalysts for more efficient and environmentally friendly synthesis of pharmaceuticals and alternative energy.

35 PHARMACEUTICALS SYNTHESIS AND NANOBIOTECHNOLOGY IBN scientists are also creating new catalysts for sustainable technology. IBN is focused on deriving nanoporous and nanocomposite catalysts that can help to reduce the cost of drug manufacturing, making cheaper medicine accessible to a wider population. It is developing rapid synthesis and screening of protein capture agents for cancer biomarker validation.

36 PHARMACEUTICALS SYNTHESIS AND NANOBIOTECHNOLOGY CARBENE-BASED CATALYSTS FOR GREEN SYNTHESIS AND ALTERNATIVE ENERGY TECHNOLOGIES New N-heterocyclic carbene (NHC) based main-chain polymer catalysts have been successfully synthesized at IBN for a variety of reactions commonly used in pharmaceuticals production. These heterogenized catalysts are inexpensive, easily functionalized, and display high activity for a wide range of substrates. They provide an attractive alternative to costly, environmentally unfriendly organophosphanes since these solid catalysts allow for ease of recovery and reuse. Carbene-based catalysts developed at IBN have also achieved a record high activity for converting biomass to furan compounds. IBN has further developed novel carbene-based organocatalysts that successfully converted carbon dioxide to methanol using hydrosilane. This effective reaction at ambient conditions has excellent potential for sequestration and conversion of greenhouse gas to biofuel. - G. Yong, Y. Zhang and J. Y. Ying, Angewandte Chemie International Edition, 47 (2008) S. N. Riduan, Y. Zhang and J. Y. Ying, Angewandte Chemie International Edition, 48 (2009) Y. Zhang, L. Zhao, P. K. Patra, D. Hu and J. Y. Ying, Nano Today, 4 (2009) M. X. Tan, Y. Zhang and J. Y. Ying, Advanced Synthesis and Catalysis, 351 (2009) Our focus is on green and environmentally friendly organic chemistry. We are particularly interested in developing nanostructured materials and catalytic systems for pharmaceuticals, green energy and sustainable technology research. DR YUGEN ZHANG TEAM LEADER AND PRINCIPAL RESEARCH SCIENTIST Polyimidazolium nanoparticles for green catalysis.

37 CATALYSTS FOR EFFICIENT PHARMACEUTICALS PRODUCTION IBN researchers have invented a one-step method to prepare NHC-palladacycles that does not require special equipment, isolation or air- and moisture-sensitive carbenes. These precatalysts provide researchers with user-friendly, easily prepared, stable and highly active synthetic tools for more efficient and environmentally friendly pharmaceutical and materials synthesis. Tokyo Chemical Industry, a leading global manufacturer and supplier of organic chemicals, has licensed this technology to commercialize IBN s new range of catalysts. - E. A. B. Kantchev, G. Peh, C. Zhang and J. Y. Ying, Organic Letters, 10 (2008) E. A. B. Kantchev and J. Y. Ying, Organometallics, 28 (2009) We are creating novel catalysts and nanostructured supports, which are essential for the efficient synthesis of drug molecules, and the effective conversionof energy in fuel cells and solar cells. PROF JACKIE Y. YING EXECUTIVE DIRECTOR AND SENIOR GROUP LEADER NOVEL MESOPOROUS MATERIALS FOR CATALYTIC APPLICATIONS IBN developed the first tri-continuous mesoporous material for catalysis, separation and drug delivery. Scientists at IBN have discovered a synthesis technique for mesoporous materials, which allows them to control the particle size and morphology, as well as the pore size and structure. The resulting tailored nanoparticles with ultralarge surface areas are attractive as catalyst supports in drug manufacturing. Their uniform nanopores and small particle sizes facilitate substrate diffusion, making them suitable for gas adsorption and separation applications. These nanoporous materials may also be used for controlled drug and gene delivery, and as host materials of nanoparticles and quantum dots. - Y. Han and J. Y. Ying, Angewandte Chemie International Edition, 44 (2004) Y. Han, L. Zhao and J. Y. Ying, Advanced Materials, 19 (2007) Y. Han, D. Zhang, L. L. Chng, J. Sun, L. Zhao, X. Zou and J. Y. Ying, Nature Chemistry, 1 (2009)

38 PHARMACEUTICALS SYNTHESIS AND NANOBIOTECHNOLOGY PROTEIN CAPTURE AGENTS FOR PERSONALIZED DISEASE DIAGNOSTICS The measurement of large panels of protein biomarkers is a highly promising approach for yielding informative disease diagnostics for personalized medicine. Currently, antibodies are widely used for detecting protein biomarkers but their cost and their chemical and biochemical instability represent a major technological bottleneck. IBN and California Institute of Technology are jointly developing stable, high-affinity protein capture agents in large quantities to replace these antibodies. They are also developing novel capture agents to target specific proteins, such as cancer-related proteins. - S. S. Lee, J. Lim, J. Cha, S. Tan and J. R. Heath, Journal of Combinatorial Chemistry, 10 (2008) We aim to prepare large quantities of stable high-affinity, high-selectivity protein capture agents. We use the protein target itself as the template for assembling its own capture agent. PROF JAMES R. HEATH VISITING INSTITUTE FELLOW We are developing high-throughput tools for robust and rapid peptide sequencing, as well as more efficient analytical tools for rapid identification of positive peptides. We are also synthesizing a wide range of artificial amino acids for in situ click screening to develop multi-ligand capture agents. DR SU SEONG LEE TEAM LEADER AND PRINCIPAL RESEARCH SCIENTIST

39 IBN PHARMACEUTICALS SYNTHESIS AND NANOBIOTECHNOLOGY GROUP AND TEAM LEADERS PROF JACKIE Y. YING EXECUTIVE DIRECTOR AND SENIOR GROUP LEADER Postdoctoral Fellow, Institute for New Materials, Germany Ph.D. in Chemical Engineering, Princeton University PROF JAMES R. HEATH VISITING INSTITUTE FELLOW Elizabeth W. Gilloon Professor of Chemistry, California Institute of Technology Postdoctoral Fellow, University of California, Berkeley Ph.D. in Physical Chemistry, Rice University DR SU SEONG LEE TEAM LEADER AND PRINCIPAL RESEARCH SCIENTIST Postdoctoral Fellow, Massachusetts Institute of Technology Ph.D. in Chemistry, Seoul National University DR YUGEN ZHANG TEAM LEADER AND PRINCIPAL RESEARCH SCIENTIST Postdoctoral Fellow, Harvard University Ph.D. in Analytical Chemistry, University of Science and Technology of China WW.IBN.A-STAR.

40 Institute of Bioengineering and Nanotechnology