NCG LabtoMarket Forum

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NCG Lab-to-Market Forum Use of Collagen
Nanofibrils in Lost Protein Technology and Other
Energy Applications Prof. G. J. Maffia November
18, 2008
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Collagen Research Group - Overview

• Collagen
• the most abundant protein found in mammals
• assembles into rope-like structures
• Processing
• collagen found in bovine or porcine corium is
  milled at Widener to recover collagen nanofibrils
  (with 75 m2/g of active surface area)
• The nanofibrils are then used in a variety of
  applications from environmental remediation to
  biotechnology/biomedical engineering

milling
Nanofibrils
Fibers
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2
3

Bovine Hide Cross-section Starting Material
Rat Stem Cells Growing Inside Collagen
Microspheres

milling and dispersion (smart material) USP
6660829 December, 2003
Environmental Extraction Filtration
Aid Flocculation and Settling
Catalyst Manufacture Photocatalyst Coating Lost
Protein Catalyst Manufacture
Biotechnology Cell Immobilization reactor
design biosensing tissue
engineering Biomolecule Delivery Controlled
Release
Miscellaneous Dispersing Agent Infrastructure Insu
lation Micro-encapsulation Medical Devices
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Manufacturing Process
US patent 6,660,829 (12/2003)
Product 1
Product 2
Product 3
Product 4
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Four Basic Products

• P1) Milled corium paste 6-10 paste
• P2) Viscous dispersion with and w/o
• additives
• CAW0.5/5/94.5
• P3) Lyophilized matrix
• controllable pore structure
• P4) Crosslinked matrix

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Commercialization Potential

• Three key aspects of the research with energy
  implications
• metal foams and catalysis
• water-water extraction
• flocculation and filtration aid

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Commercialization Potential
metal foams catalysis process
steps milling, dispersion, casting,
freezing, lyophilization, crosslinking, sinterin
g
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Commercialization Potential
Key Aspects of the work field of application
metal foams catalysis
1 mm bead
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Commercialization Potential

• Key Aspects of the work
• field of application metal foams catalysis

copper
titanium
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Collagen only no metal
Metal only no collagen
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Commercialization Potential

• Key Aspects of the work
• field of application metal foams catalysis
• High surface area
• Controllable density, porosity and morphology
• Geometry Control spheres, coatings, composites
• A platform technology use of protein
  sacrificial scaffold
• Metal foams developed by US Govt Aerospace
  Industry closest competitor
• Lower manufacturing cost than metal foams, better
  morphology and pore control
• Potential drawback is that collagen nanofibrils
  currently produced on small scale

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Commercialization Potential
water-water extraction process
steps milling, dispersion, blending, centrifug
ing (?)
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Commercialization Potential

• Key Aspects of the work
• field of application water-water extraction

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Commercialization Potential

• Key Aspects of the work
• field of application water-water extraction
• Biomolecules (including biofuels) have poor
  production economics due to the high cost of
  recovery from low concentration reactor effluents
• the collagen dispersion can be made to become
  biphasic trapping the biomolecule with minimal
  energy expenditure
• This could be platform technology for many
  aqueous separations
• Aqueous-aqueous separations are currently being
  researched, none of which use collagen
  nanofibrils
• Collagen has the advantage of a very controllable
  swelling curve and an retention of 500x its mass
  in water
• Potential drawback is that collagen nanofibrils
  are currently produced in small quantities

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Commercialization Potential

• flocculation and filtration aid
• process steps
• milling, dispersion, blending

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Commercialization Potential

• Key Aspects of the work
• field of application flocculation and
  filtration

Micron size polystyrene dust with (right) and
without (left) 1 ppm collagen nanofibril
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Commercialization Potential

• Key Aspects of the work
• field of application flocculation and
  filtration

suspended solids such as in the sludge
agglomerate rapidly and settle
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Commercialization Potential

• Key Aspects of the work
• field of application flocculation and
  filtration
• Colloidal systems agglomerate and settle when ppm
  levels of collagen nanofibrils added
• The use of collagen nanofibrils in water
  treatment and waste water remediation with
  minimal energy consumption make this a platform
  technology for a variety of systems
• Flocculants are common in environmental systems.
  Collagen nanofibrils work on a wide variety of
  systems and require minute quantities.
• Potential drawback is that collagen nanofibrils
  are currently produced in small quantities

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Technology Transfer Issues
Status of Research Market Analysis Freedom of
Operation Commercialization Strategies
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Technology Transfer Issues
Status of Research
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• Status of the research
• Collagen nanofibrils, dispersion, matrices and
  scaffolds production all ongoing at pilot scale
  (20 g/day)
• Future work collaboration needed for
  commercilization
• Major hurdle will be the scale-up of the milling
  process for the production of nanofibrils
• Funding Support status NTI, KIG,
  Osteogenics,
• USDA (in-kind)

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Technology Transfer Issues

• Application and Manufacturing
• Almost Ready for Prime Time
• Manufacturing process is controllable, reliable
  and repeatable
• Most of the process is easily scaled the initial
  milling step will require some additional
  research
• Some applications will be step-outs from existing
  processing others (like the catalysis) may be
  drop-in

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Technology Transfer Issues
Market Analysis
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Technology Transfer Issues

• Market Analysis Catalysis
• Multi-billion USD market for catalyst manufacture
• Especially for oxidation and partial oxidation
• Key Players Sud Chemie, Grace, Shell, Johnson
  Matthey, Exxon-Mobil

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Technology Transfer Issues
Market Analysis Metal Foams Open Closed
Celled metal foams variety of applications
including heat transfer, energy absorption, flow
diffusion and lightweight optics. Manufacturers
include ERG Aerospace, Metal Foam Korea, M-Pore,
Porvair, Metafoam and Recemat. - others listed
in following slides
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Technology Transfer Issues
Market Analysis Metal Foams Due to the high
cost of the material it is most typically used in
advanced technology aerospace and
manufacturing. Extremely fine-scale foams, with
cells too small to be visible to the naked eye,
are used as high temperature filters in the
chemical industry.
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Technology Transfer Issues

• Market Analysis Metal Foams
• Market in embryonic stage
• Key Players many (see following slides)
• Mostly high end applications

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Technology Transfer Issues
Suppliers of metal foams Alulight (Austria)
Aluminium foams (powder route). Alusion (Canada)
Provide aluminium foam products to the
architectural
and design industries (division of Cymat
corporation). Chand Eisenmann Metallurgical
(USA) Porous sintered materials. Cymat (Canada)
Aluminium foams (liquid metal route). Dunlop
Equipment (England) Metal foam material. ERG
Materials and Aerospace Corporation (USA) Cast
metal sponges with
open cells. Fraunhofer Institute (Germany)
Aluminium foams by powder-metallurgy. Gleich GmbH
(Germany) European dealer for Alporas aluminium
foams. Hütte Klein-Reichenbach Ges.m.b.H
(Austria) Metcomb aluminium foam
(liquid metal route). Contact
Herbert Flankl Inco (Canada) Nickel metal
sponges with open cells. IWE Greifswald
Aluminium foams (powder route).
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Technology Transfer Issues
Suppliers of metal foams Korea metal foam
(Korea) Cast metal sponges with open
cells. Metafoam Technologies (Canada)
Development and
commercialization of open-cell metal
foam. Mitshubshi Materials (Japan) Supplier of
open cell metal foams. M-Pore (Germany) Cast
metal sponges with open cells. Porvair Advanced
Materials (USA) Reticulated metal structures
(Cu,
Ni, Ti, Fe, Pt, Ag many alloys). RECEMAT
Internationals (Netherlands) Supplier of open
cell metal
foams of Nickel and Nickel alloys. Sheets
and
products. Reade Advanced Materials Open cell
metals (by electrodeposition
and casting Al, Cu, Hf,
Pb, Ni, Nb, Re, Ta,
Ti, W, Zn, Zr, steel).
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Technology Transfer Issues
Suppliers of metal foams Research Center for
Aluminum Foam (China) Research oriented
aluminium foam
company (liquid metal route). Shinko Wire Company
Ltd. (Japan) Aluminium foam, trade name ALPORAS
(liquid metal route) (in Japanese) Spectra-Mat
(USA) tungsten and molybdenum open cell sponge
components. Contact
Bob Cronk Solea (France)Porous metals and porous
metallic surfaces (gtmore) Contact Christophe
Desnoyer Ultramet (USA) Refractory ceramic and
metal metal sponges with open
cells.
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Technology Transfer Issues

• Market Analysis Aqueous-Aqueous
• Market in embryonic stage with mostly high end
  applications
• Key Players many, mostly involved with the
  recovery of organic biomolecules and pollutants

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Technology Transfer Issues

• Market Analysis
• Flocculation and Filtration
• Water treatment chemicals
• 4- 5 B with a 5 growth rate
• Key Players many (38 leading competitor)
• Ondeo Nalco, GE Betz, Arch Chemicals, Ashland
  Specialty Chemical, Buckman Laboratories,
  ChemTreat, Cytec Industries, Great Lakes
  Chemical, Kemira, Occidental Chemical, and
  Rohm and Haas
• Most chemicals sell for 2 per pound collagen
  should be very competitive with this

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Technology Transfer Issues

• Market Analysis
• Flocculation and Filtration
• Water treatment chemicals
• New Areas
• High end areas such as pathogen removal or the
  sequestering of metal contaminants have been
  demonstrated using collagen dispersions and
  matrices

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Technology Transfer Issues
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Technology Transfer Issues
Freedom of Operation
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Technology Transfer Issues

• Freedom of Operation
• USP 6660829 issued CNF production
• Earlier USP by GJM at Dartmouth expired
  related to cell culture
• New Patents Currently Being Filed

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Technology Transfer Issues
Commercialization Strategies
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Technology Transfer Issues

• Commercialization Strategies
• External/Industry collaboration is required in
  order to advance
• University position on licensing is being
  developed

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Thank You from the Collagen Research Group