Bio Nano Robotics - NASA's Institute for Advanced Concepts - USRA

BIO-NANO-MACHINESFOR SPACE APPLICATIONSPI: Constantinos Mavroidis, Ph.D., Associate ProfessorComputational Bio Nanorobotics Laboratory (CBNL)Department of Mechanical and Industrial EngineeringNortheastern University, Boston, Massachusetts

The TeamDr. C. MavroidisAssociate ProfessorMechanical Engineering,Northeastern UniversityDr. M. YarmushProfessor, BiomedicalEngineering, RutgersUniversity and MGHDr. John Kundert-Gibbs,Director Digital Production Arts,Clemson UniversityAtul DubeyPhD StudentRutgers UniversityAjay UmmatPhD StudentNortheastern UniversityGaurav SharmaPhD StudentNortheastern University

Team Structure

Introduction and Objectives• Identify and study computationally andexperimentally protein and DNA configurationsthat can be used as bio-nano-machine components• Design two macro-scale devices with importantspace application that will be using bio-nanocomponentassemblies:– The Networked TerraXplorer (NTXp)– All Terrain Astronaut Bio-Nano Gears (ATB)

The Concept• Nanorobots would constitute any “smart” structurecapable of actuation, sensing, signaling, informationprocessing, intelligence, and swarm behavior at nanoscale.• Bio nanorobots – Nanorobots designed (andinspired) by harnessing properties of biologicalmaterials (peptides, DNAs), their designs andfunctionalities. These are inspired not only by naturebut machines too.

Why bio?MotivationThe motivation behind research in the field of bio nanorobots• Several properties and functionalities (self replication, healing, adaptability,life, intelligence) exhibited by the nature (these materials) which are verydesirable.• Many mechanisms and machines(biochemical) associated with these materialsare reversible and highly efficient (ATPsynthase).• Their diversity and availability.• The applications – how nature which is madeof up molecular machines translate it intomacro application (see the figure) and hencean open source for innovative applications.• Novel way of influencing nano world withthese components – a possible industryenabler

CollaborationA truly multidisciplinary field

The RoadmapBio SensorsAutomaticfabrication andinformationprocessingDNA JointsA bio nano robotRepresentative Assemblyof bio componentsA bio nanocomputational cellDistributiveintelligenceprogramming &controlAssembled bionanorobotsA Bio nano informationprocessing componentHA a-helixBio nanocomponentsBio nano swarmsConceptual automaticfabrication floorSTEP 1 STEP 2 STEP 3 STEP 4Research Progression

Structural ElementsMacro-Nano EquivalenceMetal, Plastic PolymerDNA, NanotubesActuatorsElectric Motors,Pneumatic Actuators,Smart Materials, Batteries,etc.ATPase, VPL Motor, DNA

Macro-Nano EquivalenceSensorsLight sensors, force sensors,position sensors, temperaturesensorsRhodopsin,Heat ShockFactorJointsRevolute, Prismatic,Spherical Joints etc.DNANanodevices,Nanojoints

Assembled Bionano RobotsThe assembly of functionally stable bionano components intocomplex assemblies.Potential methodologies for assembling bio nano components:Molecular docking method is very important for the design of nanoroboticsystems. This method is utilized to fit two molecules together in 3D space

Distributive Intelligence, Programming & ControlDevelop concepts that wouldenable collaboration amongbionanorobots and hencedevelopment of “colonies”.i) Binding mechanism for swarmformationsii) Inter robotic signaling mechanisms,which would include molecularrecognition of similar functioning nanorobots and sustaining dedicatedmolecular connections.

Automatic FabricationAutomatic fabrication methodologies of such bio-nano robotsin vivo and in vitro.Floor concept of assembling bionanorobot:Different colors represent different functions in automatic fabrication mechanism. Thearrows indicate the flow of components on the Floor layout. Section 1: Basic Stimulistorage – Control Expression; Section 2: Bio molecular component manufacturing(actuator / sensor); Section 3: Linking of bio-nano components; Section 4: Fabrication ofBio-nano robots (assemblage of linked bio-nano components)

Design Philosophy and ArchitectureA. Modular Organization - Modular organization defines the fundamentalrule and hierarchy for constructing a bio-nanorobotic system. Suchconstruction is performed through stable integration of the individual ‘biomodulesor components’, which constitute the bio-nanorobot.B. The Universal Template (Bio Nano STEM System) - The modularconstruction concept involves designing a universal template for bio-nanosystems, which could be ‘programmed and grown’ into any possible Bio nanosystem in the domain of the materials used. This concept mimics theembryonic stem cells found in the human beings.

Design Philosophy and ArchitectureC. Information Processing (Memory Storage and Programming) -Capability of information processing is one of the most novel features of thebio nano systems being discussed. The design of these systems wouldincorporate the various functionalities of bio materials, such as, reversibilityand function dependence on conformational changes.D. Bio Nano Intelligence - Integrating bio-nano information storage andprogramming capability with the functionality of growth and evolution, laysthe foundation of Bio-nano intelligence.

A. Modular Organization…FunctionalityBioNanoCodeCapabilities TargetedGeneral ApplicationsEnergyStorage andCarrierMechanicalInputSensingSignalingInformationstorageSwarmBehaviorInformationProcessingEMSGFWIAbility to store energy from varioussources such as, Solar, chemical forfuture usage and for its own workingAbility to precisely move and orientother molecules or modules at nanoscale. This includes ability tomechanically bind to various targetobjects, and carry them at desiredlocation.Sensing capabilities in various domainssuch as, chemical, mechanical, visual,auditory, electrical, magneticAbility to amplify the sensory data andcommunicate with bio-systems or withthe micro controllers. Capability toidentify their locations through varioustrigger mechanisms such as fluorescenceAbility to store information collected bythe sensory element. Behave similar to aread - write mechanism in computer fieldExhibit binding capabilities with“similar” bio-nano robots so as toperform distributive sensing, intelligenceand action (energy storage) functionsCapability of following algorithms(Turing equivalent)Replication R Replicate themselves when requiredSupplies the energy required for the working ofall the bio-chemical mechanisms of the proposedbio-nano-robotic systems1. Carry moities and deliver them to the preciselocations in correct orientations.2. Move micro world objects with nanoprecision.Evaluation and discovery of target locationsbased on either chemical properties, temperatureor others characteristics.Imaging for Medical applications or for imagingchanges in Nano Structures1. Store the sensory data for future signaling orusage2. Read the stored data to carry out programmedfunctions.3. Back bone for the sensory bio-module4. Store nano world phenomenon currently notobserved with easeAll the tasks to be performed by the bio-nanorobots will be planned and programmed keepingin mind the swarm behavior and capabilitiesProgrammable1. Replicate by assembling raw components intonanorobots, and programming newly-made robotto form swarms that form automated fabricators.2. Assemble particular bio-modules as per thedemand of the situation, consistent with theForesight Guidelines for safe replicatordevelopment [Foresight Institute, 2000]

Design Philosophy and ArchitectureA. Modular OrganizationThe SPHERE (Module A)represents energy & datastorage arrangements forthe robotThe DISC representsspatial area defined forModule D and for possibleconnections with otherinner coresThe RING representsthe spatial areadefined on the innercore for the bindingof the Module B andModule CA Bio-Nano-Robotic Entity ‘ABCD’, where A, B, C and D are the various Bio Modules constituting the bionano-robot.In our case these bio modules would be set of stable configurations of various proteins and DNAs.

Design Philosophy and ArchitectureB. The Universal TemplateA basic template which could be at runtimemodified and subjected to havespecific functionality is the goal of thebio nano STEM cells.Sensing capability enhanced Bionanorobot.

A proposed modeldesigned for memorystorage capability atnano scaleDesign Philosophy and ArchitectureC. Memory Storage and ProgrammingBio nanocomputational cell

C. Memory Storage and ProgrammingThe working principle is illustrated in the following equationsPresenceof a Field Gradient1 1 ←⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯→fully reversible reaction1+IonA + ( DNA + DNA ) ( DNA ) + Trga b * APresenceof a Field Gradient1 1 ←⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯→fully reversible reaction1+IonB + ( DNA + DNA ) ( DNA ) + Trga b ** BIonC+Presenceof a Field Gradient+ ( DNA + DNA ) ←⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯→ ( DNA * ) + Trg2a 2b fully reversible reaction2CPr esenceof a Field Gradient2 2 ←⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯→fully reversible reaction2+IonD + ( DNA + DNA ) ( DNA ) + Trga b ** D___________________________________________________________4 Ions ( Input ReactsWithGenerates) ←⎯⎯⎯⎯⎯⎯⎯⎯→ Bio _ Chemical _ Center ←⎯⎯⎯⎯⎯⎯⎯⎯→ 4 TriggersGeneratesReactsWith

Design Philosophy and ArchitectureD. Bio Nano IntelligenceAxis GGrowth DirectionA bio-nanocomputational CellBlocksAxis IInformation Processing& sequencing axisChannelsA model is being proposed which describes programming, learning and hence evolving asone combination of events which can quantitatively describe intelligence. Ionic strength andtheir variations could be few of the important variables responsible for the behavior of a bionanorobotic system.

D. Bio Nano Intelligence• Axis I, is the axis where the information is filtered and various componentsare sequentially isolated and stored in the bio-nano computational cell. Thestimuli obtained by activation of the first block, triggers a reaction, whichactivates the subsequent blocks along the Axis I.• Axis G is the Growth Direction. Along this axis copy of the initial data ismade. Once a row is finished along the Axis I, the Axis G elements areactivated. And again the sequencing along the Axis I would start. A singlestimulus could trigger multiple outputs through this mechanism. Axis Gwould also enable parallel computations, thereby accelerating the responseto a given input. This is typical of an intelligent living system, where thepast stimuli are responded to faster when they felt.• Ion types could be related to the variations in behavior and IonConcentration could be related to the intensity of the behavior of a bio-nanorobotic system.

Control of Bionano Robotic SystemsInternal ControlPassive control - depends upon themechanism of bio chemical sensing andselective binding of various bio moleculeswith various other elements.Active control - ‘active’ control mechanismhas to be designed for the nanorobots suchthat they can vary their behavior based onsituations they are subjected to, similar to theway macro robots perform.This requires the nanorobot to beprogrammable and have an ability formemory storage. Professor Ehud Shapiro’slab has devised a biomolecular computerwhich could be an excellent method.External ControlThis type of control mechanism employsaffecting the dynamics of the nanorobot inits work environment through the applicationof external potential fields.Researchers (Prof Sylvain Martel) are usingMRI as an external control mechanism forguiding the nano particles.An MRI system is capable of generatingvariable magnetic field gradients which canexert force on the nanorobot in the threedimensions and hence control its movementand orientation. But this method has somelimitations on very accurate precision of thecontrol.

Experimental and Computational MethodsVPL Motor at (a) neutral and (b) acidic pH. a) Front view of the partially α-helical triplestranded coiled coil. VPL motor is in the closed conformation; b) VPL Motor in the openconformation. The random coil regions (white) are converted into well defined helices andan extension occurs at lower pH• Molecular modelling techniques in sync with extensive experimentations would form thebasis for designing these bio-nano systems.• Protein based linear motor, Viral protein linear (VPL) motor. VPL motor changes itsconformation due to a change in its pH. This change in conformation gives rise to forcesand linear displacements. It is a 36 amino acid peptide from the hemagglutinin protein ofthe influenza virus. This 36 amino acid peptide is termed Loop-36.ab

Experimental and Computational Methods• To begin predictions of the dynamic performance of the peptide (i.e. energy andforce calculation) we are performing Molecular Dynamics (MD) Simulations thatare based on the calculation of the free energy that is released during the transitionfrom native to fusogenic state, using the MD software CHARMM.• Other then the Loop-36 our computational and experimental group are focusing onpeptides which don’t require high energy molecules and had been shown to undergosubstantial conformational variations following changes in their environment. RTX β-Rolland Elastin are at the center of focus of our research.• Our group is integrating these efforts with Virtual Reality based design techniques.Haptic interface is under construction which would help us evaluate in real-time the forcesand its variations of the various molecules. In the next step we will integrate theexperimental and computational process by making a peptide-AFM-Phantom-VMD-NAMDsystem.

Space ApplicationsOur current research is focused on two main space basedapplications:• Networked TerraXplorers (NTXp)– Mapping and sensing of vast planetary terrains• All Terrain Astronaut Bionano Gears (ATB)– Enhanced health management and protection system for astronauts

Networked TerraXplorers (NTXp)Mapping of vast planetary terrainsA realistic scenario where the Networked TerraXplorers (NTXp) are employed.These meshes would be launched through the parachute and these would be spreadopen on the target surface. These NTXps could be launched in large quantities(hundreds) and hence the target terrain could be thoroughly mapped and sensed. Asingle NTXp could run into miles and when integrated with other NTXPs could covera vast terrain.

Networked TerraXplorers (NTXp)Mapping of vast planetary terrainsPrinciple of OperationThe bio-nano robots will move inside the channels of the networkand would have ‘limited’ window of interaction, through specialvalves with the outside environment. They will interact with theoutside terrain and chemically sense the presence of water or othertargeted resources / minerals. The micro channel would be designedin various layers, making it ready for the harsh conditions on theplanetary surface, such as: Radiations, Temperature, pressure etc.ChannelsOuter LayerBio-NanoRobotsNodesExplorationDirection Along thechannelsA ChannelInner Layer

Micro Networked TerraXplorers (NTXp)Mapping of vast planetary terrains• Micro Networked TerraXplorers, is the extension of the NTXp concept.In this concept, the bio-nano robots would perform sensory function, butthe signaling function would be performed by the “communicationmicrochip” integrated with the bio-nano system. This microchip wouldsignal the data gathered to the central receiver. This Micro NTXp wouldbe very small in size (few mms or smaller) and could be sprayed from theair borne rover or orbiter to the desired location. These devices wouldform a sensory network amongst them and would act in collaborative anddistributive way.SolarpanelsSwarm of Micro NTXpMicro ChipProtective sheet - SensoryRegion

The All Terrain Bionano (ATB) Gears for AstronautsOuter LayerInteracting withthe Space SuitMiddle LayerSignaling &Information StorageInner LayerInteracting with theAstronautThe layered concept of the ATB gears. Shown are three layers for the ATB gears. The inner layerwould be in contact with the human body and the outer layer would be responsible of sensing theouter environment. The middle layer would be responsible for communicating, signaling anddrug delivery.

The All Terrain Bionano (ATB) Gears for AstronautsBreach sealing mechanism: The mechanism of covering breach by theATB gear is shown. The bio-nano robots would flow through variouslayers and bind amongst themselves and form a cover. Self assemblyof the bionano robots is one of the properties employed for suchmechanism.Covering the breachsurface and henceprotecting thesubsequent layerSelf assembly in layersleading to coverage ofthe breach

Identification of Space Requirements• Work environment – Targeting Mars environment• Temperature– Maximum of around 20° C (68° F) and minimum of -140° C (-220° F)• Pressure– As low as 6.8 millibars (the average pressure of the Earth is 1000millibars)• Radiations– ultraviolet (UV) radiations is the main source of radiations– between the wavelengths of 190 and 300 nm• Sensory targets in space – water, oxides, minerals…what else!

Identifying Biocomponents for SpaceIn general there is a positive correlation between the degree of stability(such as thermophilicity) of the source organism and the degree ofstability (thermostability) of both their intracellular and extracellularproteins. Hence we are studying various micro organisms which exist inthe extreme conditions and further isolating various bio components to beused as:i. Sensorsii. Actuators and manipulatorsiii. Signalingiv. Information Processing

Extreme Micro OrganismsEukaryotes inExtremeEnvironmentsDefinitionOperatingRegimeName of the OrganismsThermophilesMicro organismswhich can exist athigher temperaturesThe range is prettybroad. The limit oflife is expected tobe around 140degree centigrades.1. Cyanidium caldarium - its optimalgrowth temperature was 45ºC and themaximum temperature at which growthoccurred was 57ºC. 2. Cells like thearchaean Pyrococcus grow above 100ºC.PsychrophilesMicro organismswhich can exist atcolder temperaturesWater is thesolvent for life andmust be present in aliquid state forgrowth to occur.This sets a practicallower limit forgrowth slightlybelow 0ºC.Cold Shock protein - CspA a major coldshock protein of E Coli.Cold-acclimation protein (CAPs)- a secondgroup of protein that are involved in thelow-temperature growth of psychrophilicbacteria and yeasts. (Pseudomonassyringae)Ice-nucleatingproteins forms ice crystals on leaves andflowers (-2 to -5 C). (Pseudomonas,Erwinia, Xanthomonas)AcidophilesMico organisms whichcan exist in acidicenvironment (pH 3 orless). The internal pHof acidophiles has beenmeasured between 5 to7 C.Less than pH of 3.T. ferrooxidans, Acontium cylatium,Cephalosporium spp., and Trichosporoncerebriae

Extreme Micro OrganismsAlkalophilesA micro organismwhose optimum rate ofgrowth is observed atleast two pH unitsabove neutrality orabove 9 pH.9 - 11 pHSpirulina, B. alcalophilusXerophilesA micro organismwhich can survive indriest environments.Metallogenium,Pedomicrobium, and lichenssuch as Rhizocarpongeographicum, Aspicilia cinerea, Caloplaca saxicolaRadiation resistant organismsWhich can sustainionizing radiationsWhen exposed to 1.5 millionrads of ionizing radiation (adose 3000 times higher thanwould kill organisms frommicrobes to humans),Deinococcus repaired thedamage to its shattered DNAin a matter of hours.1. Deinococcus radiodurans 2.Halobacterium - a master of thecomplex art of DNA repair. Thisbacteria has survived normallylethaldoses of ultravioletradiation (UV), extreme dryness,and even the vacuum of space.Evolving to cope with a saltylifestyle could explain whyHalobacterium is so good atsurviving radiation and otherravages.

Biocomponents for Space ApplicationsSensorsi. Biosensors based on metal binding proteins such asPhytochelatins and metallothioneins (MTs).ii. Heat Shock Factoriii. ElastinStructural modules (membrane or static structure construction)i. S-Layer proteins - these are the single most abundant polypeptidespecies in the thermophilic archaeobacterial.ii. Tetraether lipids

Biocomponents for Space ApplicationsInformation Processing modulei. DNA or protein arraysii. Molecular switches – sensitive to certainparameters, such as, light, receptorproteins.Some of the thermally stable enzymesEnzymeOrganismPullulanaseRNA PolymeraseSuccinate thiokinaseSulphur oxygenaseTopoisomerase ITransglucosylasePyrococcus furiosusThermoplasma acidophilumSulfolobus acidocaldariusThermoproteus tenaxDesulfurococcus mucosusThermoplasma acidophilumAcidianus brierleyiSulfolobus acidocaldariusDesulfurococcus mucosus

Sensor – Signal DynamicsSiin→{ f , g...}n{ ( , )}is the signal generated per bio sensorSout = p ∑ ai f big the net output signal from the Outer sensory system1The initially sensed physical parameter (say temperature) which was sensed by twoparameters (f, g) is now corresponded to three signaling parameters (x, y, z) defined byfunction β.Physical parameterto be sensedHardware InterfaceAmplificationOuterSensor iS outInnercorrespondence matrixS fg= β(x, y, z)Other bio modulesS outAmplificationModuleACorrespondenceTableS fg= β(x, y, z)

System Level Design of NTXpThree tier skin design for the NTXp1. The thermal insulating and pressure sustaining layer of the NTXp (shown inblack).2. Exchange layer of the NTXp (shown in blue). This is responsible for theexchange of particles of the parameter information from the outer layer to the innersensing layer.3. Inner sensing layer of the NTXp, which is responsible for the actual sensing.From this layer the actual sensory modules of the NTXp would be attached.

Animation of NTXp

AcknowledgmentsNASA Institute of Advanced Concepts(NIAC) Phase II Grant, September 2004http://www.niac.usra.edu/