Bio Nano Robotics - NASA`s Institute for Advanced Concepts

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Transcript Bio Nano Robotics - NASA`s Institute for Advanced Concepts

Bio-Nano-Machines for Space Applications
Presented by: Ajay Ummat (Graduate Student, Northeastern University, Boston)
PI: Constantinos Mavroidis, Ph.D., Associate Professor
Computational Bio Nanorobotics Laboratory (CBNL)
Dept. of Mechanical & Industrial Engineering, Northeastern University, Boston, Massachusetts
Researchers
Computational
Experimental
Dr. M. Yarmush
Dr. C. Mavroidis
Associate Professor
Mechanical Engineering,
Northeastern University
Ajay Ummat
PhD Student
Northeastern University
Atul Dubey
Gaurav Sharma
PhD Student
Rutgers University
PhD Student
Northeastern University
Kaushal Rege
Research Fellow
MGH / Shriners
Professor, Biomedical
Engineering, Rutgers
University and MGH
Monica Casali
Zak Megeed
Research Fellow
MGH / Shriners
Research Associate
MGH / Shriners
Consultants
Biology and
Biomedical Engineering
Dr. Marianna Bei, MGH
Computational
Dr. Elias Gyftopoulos, MIT
Dr. John Kundert-Gibbs,
Clemson University
Dr. Jeff Ruberti, NU
Dr. David Budil, NU
Micro / Nano
Manufacturing
Dr. Ahmed Busnaina,
NU
Dr. Silvina Tomassone, Rutgers
Chemistry and
Chemical Engineering
Dr. Albert Sacco, NU
Dr. Demetri
Papageorgiou, NU
Dr. Fotis Papadimitrakopoulos,
UCONN
Introduction and Objectives
• Identify and study computationally and
experimentally protein and DNA configurations
that can be used as bio-nano-machine components
• Design two macro-scale devices with important
space application that will be using bio-nanocomponent assemblies:
– The Networked TerraXplorer (NTXp)
– All Terrain Astronaut Bio-Nano Gears (ATB)
The Roadmap
Automatic
fabrication and
information
processing
Bio Sensors
A bio nano
computational cell
DNA Joints
A bio nano robot
Representative Assembly
of bio components
Distributive
intelligence
programming &
control
A Bio nano information
processing component
Assembled bio
nanorobots
HA a-helix
Bio nano
components
Bio nano swarms
STEP 1
STEP 2
STEP 3
Research Progression
Conceptual automatic
information floor
STEP 4
Space Applications
Our current research is focused on two main space based applications:
• Networked TerraXplorers (NTXp)
– Mapping and sensing of vast planetary terrains
• All Terrain Astronaut Bionano Gears (ATB)
– Space radiation detection & protection system
Space Conditions / Design Requirements
Space Atmospheric Environment
• Targeting Martian environment
• Atmosphere  Carbon-di-oxide for energy production for bionano robots.
Certain micro organisms – “Methanogens” (H + CO2)
• Temperature  -140 to 20 degree C (require thermal insulation and
thermally stable bio-components)
• Pressure  6.8 millibars as high as 9.0 millibars (1000 millibars on earth)
– Materials of sustaining internal pressures
– Bio-components which can sustain in lower pressures
– Transport mechanism through skin layer (NTXp)
Space Conditions
• Topography  Scale of the bio nano machines (within meters or miles) and
the area of landing and deployment
• Local dust storms  The design for NTXp – capable of flowing through the
local storms or resist it or both
• Radiation  UV radiations between the wavelengths of 190 and 300 nm.
Strong oxidants on the upper surface of Mars (radiation resistant and
oxidant resistant skins!)
Identification of Bionano Components
• Focusing on components from micro-organisms
• A positive correlation The degree of stability of the organism  The degree of stability of their
proteins
• Studying enzymes (for their dynamics and model and ease of accessibility)
- One key component is - RNA Polymerase
- Found in many micro organisms - Thermoplasma acidophilum, Sulfolobus
acidocaldarius, Thermoproteus tenax, Desulfurococcus mucosus
Extreme Micro - Organisms
D. radiodurans
• Deinococcus radiodurans
• Cold-acclimation protein – a protein from
Pseudomonas
• Some key attributes required for the
bio nano machines and components:
– Radiation resistant
– Thermal resistance (high / low)
– Acidic environment resistant
– Dry condition resistant
Halobacterium
Computational Framework
Characterization of Bionano Components
• A control mechanism (chemical pathway) and its dependency on external
parameters (such as, pH, temperature, chemical signals, enzymes)
• The change in the external environment triggers changes in the bionano
component:
- conformation changes
- variations in the pattern of their self-assembly
•
These changes (for instance) demonstrate motion and a desired trajectory
•
Reversibility
•
Synchronization of individual bio-components
•
Stochastic, less understood dynamics, complex chemical pathways
Computational Framework
• Identification of the protein from the mentioned organisms 
characterization with respect to the following three main parameters:
- high temperature variations
- dry conditions
- space radiations
• Stability analysis  Stability in various conditions is desired, such as, dry
conditions, high temperature variations and radiations.
Sdry  f ( x1a ;y1b ;....;t )
S temp  g ( x2 j ;y2 i ;....;t )
S radiations  h( x3 v ;y3u ;....;t )
• The overall stability is a complex variable of all the individual stabilities



Snet  F ( S dry
; Stemp
; Sradiations
;t)
Framework for bio molecular dynamics
Reversibility Dynamics
• Reversibility dynamics in context of Variational dynamics
Space Radiations on Bionano System
• Radiations can produce many effects
– break bonds, change the structure, destroy the amino acid residues, form other
bonds
• Coupling of radiation at atomic level
– Hamiltonian for Radiation is coupled to the atomic system
H  H RAD  H ATOM  H
–
''
H ''the term coupling the electrons of the atom with the radiation. Radiations
can produce many effects
– break bonds, change the structure, destroy the amino acid residues, form other
bonds
•
is the sum of A coupling terms Hn  H 
''
A
H
n
Space Applications – Networked TerraXplorers (NTXp)
Networked TerraXplorers (NTXp)
Mapping of vast planetary terrains
A realistic scenario where the Networked TerraXplorers (NTXp) are employed. These
meshes would be launched through the parachute and these would be spread open on
the target surface. These NTXps could be launched in large quantities (hundreds)
and hence the target terrain could be thoroughly mapped and sensed. A single NTXp
could run into miles and when integrated with other NTXPs could cover a vast
terrain.
Detailed Mechanism of NTXp
System Level Design of NTXp
A
C
B
Design Parameters & Constraints
• External sensing  Creation of ‘tough’ external micro channels
• Reaction initiation  Presence of charges (+/-) on the NTXp surface
• Skin  Existence of an external insulating and radiation resistive layers
• Intermediary exchange layer  Small tubular structure for enabling
active transport of ions or charges across
- Connecting the micro channels and the bio-nano sensory module.
• Inner sensing layer  Sensing the absorbed constituents and transferring
the information of the measured parameters to the signaling module.
Sensor – Signal Dynamics
• Capable of converting the sensed parameter to a parameter which could
be used for signaling
• Form  flow of electrons, or variations in the concentration of ions and
their gradients
Flow of Signaling Parameters
Sini { f , g...}
n
Sout  p{ S }
i
in
1
n
Sout  p{ (ai f , bi g )}
1
n
I p{ (ai f , bi g )}
1
• This correspondence table decodes the input variables, f and g (or more)
into pure signaling variables, say, (x, y, z).
• Decoding  reaction between the sensory input and the signaling
module
Nanofluidic Transport Mechanisms
• Nanofluidics actuator / pump for NTXp transport mechanism
Space Applications – All Terrain Bionano (ATB)
The All Terrain Bionano (ATB) Gears for Astronauts
Outer Layer
Interacting with
the Space Suit
Middle Layer
Signaling &
Information Storage
Inner Layer
Interacting with the
Astronaut
The layered concept of the ATB gears. Shown are three layers for the ATB gears. The inner layer
would be in contact with the human body and the outer layer would be responsible of sensing the
outer environment. The middle layer would be responsible for communicating, signaling and
drug delivery.
Space Radiation – Molecular Damage
• Space radiation – damage to DNA, breaking of bonds, mutations leading to
cancerous conditions
• Monitoring of the space radiations for the astronauts is the key requirements.
Our existing design deals with radiation detection
Equivalence of Damage Effects
• Health hazards from the space radiations - creating equivalence energetically
System Level Design of ATB
Overall Structure of Layer A on the ATB
• Structure of the Layer A – vertical as well as horizontal directions
• Non – continuum design (in patches)
• Complimentary acceptor layer for electronic connections
Design of Layer - A
• A surface view of the
radiation detection layer –
the probabilistic reaction
layer is represented by
spheres.
• The molecular components utilized
to make these reaction pathways
• Survival of the molecular
component
The Number Game – Homological Settings
• Represents maximum probability regime for the reaction.
• Contains all the machinery (bionano robots) which will react with the
radiation
Probabilistic Reaction Centers
•
Sphere  modular design strategy
•
Probabilistic arrangement of radiation reactants and their signaling
pathways
•
Electron / ionic transport reactions
Fe+++ + e- « Fe++
Electron Transfer Reactions
•
Electron transfer reactions plays a key role in bioenergetics
•
Fermi’s Golden Rule describes the rates of the reactions
• Light (radiation?) triggered electron transfer initiation  takes place
in the reaction centers of the Layer A
Structure Of The Photosynthetic Reaction Centre From
Rhodobacter Sphaeroides Carotenoidless Strain R-26.1
Radiation Resistant Bacteria
The many characteristics of D. radiodurans:
•
An extreme resistance to genotoxic chemicals
•
Resistance to oxidative damage
•
Resistance to high levels of ionizing and ultraviolet radiation
•
Resistance to dehydration
•
A cell wall forming three or more layers
Repairs chromosome fragments, within 12-24 hours
Uses a two-system process
i. Single-strand annealing  single strand re-connections
ii. Homologous recombination  double-strand patch up
Deinococcus radiodurans
•
RecA protein  responsible for patch up and associated reactions for DNA repair
•
This bacterium might contain space resistant proteins and other mechanisms
Experimental Work
• Peptide Selection – Loop 36 (chain of 36 amino acids)
•
•
•
•
Protein Expression
Protein Purification
Site-Directed Mutagenesis
Characterization of Protein Conformation as a Function of pH
- Circular Dichroism Spectroscopy
- Nuclear Magnetic Resonance (still to perform)
Future Activities
• ATB gears for astronauts
a) Design the reaction mechanism for radiation detection for ATB
b) Design a detector layer complimentary to the Layer A
c) Integration with the electronic systems
• NTXp
a) Surface chemistry (water / mineral) detection network
b) Multi channel pumping / actuating mechanism for transport
c) Space condition tolerant outer skin for NTXp
Future Activities
• Computational framework
a) Integrate homology modeling of protein to expedite the design process
b) Computationally analyze the effect of radiation
c) Analyzing the radiation effects in ATB and how the ion / electron
transfer effects could be related to intensity of radiation damage.
• Experimental
a) Characterization of various bio-nano components
b) Techniques from NMR would be used to exactly characterize the
peptide structure when it changes its conformation
c) Explore the radiation resistant bacterium Deinococcus radiodurans for
possible radiation resistant bio-mechanisms and proteins
d) Experiments with carbon nano tube structures and bio-nano components
Publications / Presentations
• Chapter in CRC Handbook on Biomimetics - Biologically Inspired
Technologies, Editor: Yoseph Bar-Cohen, JPL
• Chapter in The Biomedical Engineering Handbook, 3rd Edition, Editor: M.
L. Yarmush,
• Paper Presented at the 7th NASA/DoD Conference on Evolvable Hardware
(EH-2005), Washington DC, June 29 - July 1, 2005
• Interview at The Scientist Volume 18 | Issue 18 | 26 | Sep. 27, 2004
“Alternative Energy for Biomotors”
• Interview at the http://science.nasa.gov/
• Our research webpage: http://www.bionano.neu.edu
Acknowledgments
NASA Institute of Advanced Concepts
(NIAC) Phase II Grant, September 2004
http://www.niac.usra.edu/
Thank You