1. 18 June, 2015 Printing therapeutic nanobots: Nanoscale
3D-printing in pharmaceutical R&D a Pistoia Alliance Debates
webinar chaired by Jim McGurk 2. This webinar is being recorded 3.
PistoiaAlliance Panellists Nanoscale 3D-printing in pharmaceutical
R&D 318 June, 2015 Jim McGurk is Senior Director and Global
Head of Data Architecture for Daiichi- Sankyo R&D Informatics.
His current position involves development and implementation of
master data management and governance for the Global R&D
organization. He is also responsible for creating and implementing
a 'Big Data' strategy; providing internal capabilities for
accessing, managing and analyzing external/public data sources. Jim
has more than 20 years experience in software and system
development in pharmaceutical discovery and development, as well as
developing strategic directions driving architectural, software and
hardware decisions. Ahmed A. Busnaina, Ph.D. is the William Lincoln
Smith Chair Professor, University Distinguished Professor, and
founding Director of National Science Foundations Nanoscale Science
and Engineering Center (NSEC) for High-rate Nanomanufacturing and
the NSF Center for Nano and Microcontamination Control at
Northeastern University, Boston, MA. Prior to joining Northeastern
University in 2000, he was a professor and a director of the
Microcontamination Control Lab at Clarkson University from
1983-2000. Dr. Busnaina specializes in nanoscale printing of 2D and
3D structures for devices and sensors. He is an associate editor of
the Journal of Nanoparticle Research, and is a fellow of the
American Society of Mechanical Engineers and the Adhesion Society.
Dr. Utkan Demirci is currently an associate professor at Stanford
University School of Medicine, Canary Center Early Cancer
Detection. He leads a group of 20+ researchers focusing on micro-
and nano-scale technologies. The Demirci Bio-Acoustic MEMS in
Medicine Labs (BAMM) laboratory specializes in applying micro- and
nanoscale technologies to problems in medicine at the interface
between micro/nanoscale engineering and medicine. Our major
research theme focuses on creating new microfluidic technology
platforms targeting broad applications in medicine. In this
interdisciplinary space at the convergence of engineering, biology
and material science, our goal is to create novel technologies for
bioprinting, disposable point-of-care (POC) diagnostics and
monitoring of infectious diseases, cancer and controlling cellular
microenvironment and microscale tissue engineering applications. 4.
Scalable Nanoscale Printing for Sensors, Electronics, Medical and
Materials Applications Ahmed Busnaina, William Lincoln Smith
Professor and Director, Northeastern University NSF Nanoscale
Science and Engineering center for High-rate Nanomanufacturing
www.nano.neu.edu www.nanomanufacturing.us 5. Printing offers an
excellent approach to making structures and devices using
nanomaterials. Current electronics and 3D printing using inkjet
technology, used for printing low-end electronics, flexible
displays, RFIDs, etc. are very slow (not scalable) and provide only
micro-scale resolution (20 microns). 20 microns was the silicon
electronics line width in 1975. Even with these scale limitations,
the cost of a currently printed sensor is 1/10th to 1/100th the
cost of current silicon-based sensors. Printed Electronics is a
$50B industry projected to reach $290B in 2025. Current
Technologies Using Nanomaterials to Make Electronics and Sensors?
6. Directed Assembly of Nanoparticles, Carbon Nanotubes and
Polymers 50 nm50 nm 50 nm copper fluorescent PSL fluorescent silica
30 m 5 m Metal II Metal I SWNT Bundles Multiple polymer systems,
Rapid Assembly, multi-scales CNTs Rapid, multi-scale Assembly
Nanoparticle Rapid, multi-scale Assembly (ACS Nano 2014) 7. WSiO2
Damascene Templates for Nanoscale Offset Printing Silicon-based
Hard Templates PEN PIPolymer-based Templates Assembled SWNT
Assembled Particles Advanced Materials, 2015 8. 3-D nanostructure
manufacturing process using nano-colloids (Northeastern U.)
Manufacturing of 3-D nanostructures using directed nanoparticle
assembly process. (A and B) NPs suspended in aqueous solution are
(A) assembled and (B) fused in the patterned via geometries under
an applied AC electric field. (C) Removal of the patterned
insulator film after the assembly process produces arrays of 3-D
nanostructures on the surface. (D) Scanning electron microscopy
(SEM) image of gold nanopillar arrays. Economic approach. MC Roco,
Nov 2 2014 ACS Nano, April 2014 9. Leveraging the directed assembly
and transfer processes developed at the CHN, Nanoscale Offset
Printing has been developed. The ink is made of nanoparticles,
nanotubes, polymers or other nano- elements that are attracted to
the printing template using directed assembly. Introducing
Nanoscale Offset Printing Nanoscale Offset Printing Template
Nanoscale Offset Printing System NanoOPS Includes Six Modules: 1.
Hexagon Frame Module 2. Template Load Port Module 3. Directed
Assembly Module 4. Mask Aligner Module 5. Transfer Module 6.
Template Load Port Module 1 2 3 4 5 6 This approach offers faster
printing with a 1000 times smaller that inkjet or 3D printing.
NanoOPS Videos on Youtube: From Lab to Fab: Pioneers in
Nano-Manufacturing: https://www.youtube.com/watch?v=tZeO9I1KEec
NanoOPS at Northeastern University:
https://www.youtube.com/watch?v=2iEjIcog774 10. Nanoscale Science
Directed Assembly and Transfer Energy Electronics Flexible
Electronics CNTs for Energy Harvesting Assembly of CNTs and NPs for
Batteries What Could We manufacture with Mul scale Offset Prin ng?
SWNT & NP Interconnects SWNT NEMS & MoS2 devices Multi-
biomarker Biosensors 1 0 m m Drug Delivery Antennas, EMI Shielding,
Radar, Metamaterials Materials Bio/Med 2-D Assembly of Structural
Apps. 11. Bio and Chem Sensors Functionalized SWNTs 4 m 25 0 m
Band-Aid Sweat Glucose & lactate sensor Chemical H2S Sensor
Cancer and cardiac diseases. Detection is 200 times lower than
Current technology Sensors for E. coli bacteria, viruses, and other
pathogens Supporting printed electronics for sensor systems 12.
Flexible CNT Bio Sensors for Glucose, Urea and Lactate in Sweat or
Tears 2 m200 nm Functionalized SWNTs Gold PEN 4 m 250 m 1 m 200 nm
CNT Sensors have been also used to detect viruses, bacteria and
antibiotics (in Blood, water or air) 13. in-vivo biosensor (0.1 mm
x 0.1 mm) Tested for detected with biomarkers for prostate (PSA),
colorectal (CEA), ovarian (CA125) and cardiac diseases. Detection
limit: 15 pg/ml Current technology detection limit is 3000 pg/ml
Publications: Langmuir Journal, 27, 2011 and Lab on a Chip Journal,
2012 US Patents: Multiple biomarker biosensor: (US 2011/0117582
A1), 2 more filed patents Multiple-biomarker detection High
sensitivity Low cost Low sample volume In-vitro and In-vivo testing
Cancer and Cardiac Disease Optical Biosensors 14. Novel Drug
Manufacturing for Oral Delivery of Poorly Soluble Drugs 1) Directed
assembly of dissolved drugs into nanorods 2) Delivery of drug in
the blood with subsequent tumor targeting 14The eudragit polymer
can be dissolved at a specific pH value to release the drugs in the
desired region of intestine. Problem: More than 40% of new chemical
entities (NCEs) and anti-cancer agents are insoluble in water and
cannot be taken orally. Solution: Fabrication of drug-loaded
micelles into 3-D nanorods. 15. What is Unique about our Approach?
15 Chauhan V.P. et al., Angew Chem Int Ed Engl . 50, 1141711420
(2011). Ryan M. Pearson et al. MRS Bulletin, 39, 2014. K. Huang et
al., ACS Nano 6 , 4483 ( 2012 ). H. Cabral et al. , Nat.
Nanotechnol. 6 , 815 ( 2011 ). A. Pluen et al., Biophys. J. 77 ,
542 ( 1999 ). Effective penetration of NPs through the tumor is
determined by the particle size and shape. Most studies focus on
the oral drug delivery of drug in the form of nanoparticles, which
have limited penetration into tumors. It has been shown that
nanorods would penetrate tumors faster and more efficient than
nanoparticles. 16. Novel Drug Manufacturing for Oral Delivery of
Poorly Soluble Drugs 16 100nm Paclitaxel drug loaded micellar
nanorod Acetaminophen drug assembled into nanoscale vias
Advantages: Poorly water-soluble drugs orally acceptable Small size
nanorods (~100nm) high permeability, effective transport through
intestines Controlled size and shape sufficiently high and fixed
drug dosage Controlled aspect ratio enhanced cell uptake better
bioavailability Composite drugs overcome multi drug resistance
Before Assembly After Assembly 17. Utkan Demirci, PhD Department of
Radiology Stanford University School of Medicine Canary Center for
Cancer Early Detection Electrical Engineering (by Courtesy)
Scaffold-free 3-D cellular assembly [email protected] 18.
Background-Tissue Engineering Strategies Top-down strategy
Sculpting a large piece of biomaterial into a well-shaped and
size-controllable scaffold for tissue constructs Challenge: Hard to
control cell distribution and microenvironment. Bottom-up strategy
Assemble microscale cell encapsulating building blocks into large
tissue constructs Challenge: Require biocompatible
intrinsic/extrinsic mechanism to assemble building blocks Soft
Matter, 2009,5, 1312-1319 19. Trends in Biotechnology, 2015 20. 3D
Micro-Masonary of Tissue Constructs UV light Photomask Prepolymer
Solution Glass Slides TMS/PMA coated glass Hydrogel Unit 21. 3-D
Microgel Assembly Technologies Nat. Comm. 2014 Adv. Mater. 2013
Adv. Mater. 2013 Adv. Mater. 2012 Biomaterials 2012
Biomicrofluidics 2012 Can we build complex 3-D constructs that
would mimic native tissues, e.g. for applications in drug testing?
22. Glass slide 500um GelMA without neuron Neural Experiments Over
Gel Size Control 100um GelMA with neuron axon Control 23. Spatial
Size Control 24. Robots to Manipulate Single Gels In collaboration
with Dr. Metin Sitti-CMU. 25. Inspiration: Faraday waves (FWs)
Faraday waves: Standing waves arise through a parametric
instability on the surface of a vertically oscillated uid layer.
Wavelengths: micrometer scale to millimeter scale Diverse forms:
stripes, squares, hexagons, quasi-periodic forms etc. Easy control
of topography by frequency and amplitude Source: Miles et al.,
Annu.Rev.Fluid Mech,22:143,1990 M Faraday 26. Spheroid Assembly 27.
Typical Patterns 28. High throughput assembly system System
Throughput Max freq Feature Old 1/ batch 200 Hz New 6/batch >300
Hz Compatible with multiwell plate Old system New system 29.
Retrieval of Constructs for Long-term culture 30. Biopreserving
Microfluidic Bioprinted 3-D constructs 31. We can grow, maintain
and cryopreserve embryoid bodies a microfluidic chip Guven et al,
Stem Cell Trans. Med. 2015 Microfluidic Systems: A Platform for
Precision Medicine Viability Before cryopreservation After
cryopreservation BrdU prolieration assay 32. Osteocalcin GFP HUVEC
GFP HUVEC Osteocalcin Bioprinting pre-vascularized osteogenic
constructs 100m 200m 100m Mimicking the native histology 33. 3-D
bioprinted and patterned EGFR2 mutated (red) and nave (green) lung
cancer cells. Migration Studies in Cancer Microenvironment 34.
Conclusions & Future Directions (i) Precision bioengineering
method to create and analyze development and function of specific
neural circuits (ii) Our laboratorys mission is applying nano and
micro-scale technologies to real problems in medicine with impact
at the clinic. (iii) Non-invasive methods including Magnetic and
Acoustic Fields are promising technologies to build more complex 3D
architecture to mimic the native tissue microenvironment. (iv) We
can preserve function of stem cells on chip differentiated to
ovarian (v) We need the ability to preserve FUNCTIONAL vascularized
cell, tissue, organs preserving morphology, mechanics, and biology.
35. Panellist debate 36. Audience Q&A Please use the chat /
question / hand-raise functions in GoToWebinar 37. PistoiaAlliance
We will set up all attendees on IP3 http://ip3.pistoiaalliance.org/
Nanoscale 3D-printing in pharmaceutical R&D18 June, 2015 38.
Sustaining translational data for secondary use Join us for the
next Pistoia Alliance Debates webinar, Wednesday 15th July @
11am-midday Eastern
https://attendee.gotowebinar.com/register/7562549094912217345 39.
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