NIST!ABMS

Workshop(to(Develop(a(Metrology"

Roadmap'for'Synthetic'Biology

July"12,"2013,"Imperial"College,"London,"United"Kingdom

Hosted"by"the"National"Institute"of"Standards"and"Technology"! Advances"in"Biomedical"

Measurement"Science"(ABMS)"Program

Co!hosted"by"Imperial"College,"the"National"Academy"of"Sciences,"and"the"BioBricks"Foundation

Organizers

Sarah%Munro,%NIST.ABMS%Program

Marc%Salit,%NIST.ABMS%Program

Participants

Catherine%Ainsworth,%Imperial%College%

Jacob%Beal,%BBN%Technologies

Parag%Chitnis,%National%Science%Foundation

Vincent%Danos,%University%of%Edinburgh

Kim%de%Mora,%iGEM%Foundation

Camille%Delebecque,%Synbio%Consulting

Rob%Dickinson,%Imperial%College

Alistair%Elfick,%University%of%Edinburgh

Drew%Endy,%Stanford%University%& BioBricks%Foundation

Douglas%Friedman,%National%Academy%of%Sciences

Emma%Frow,%University%of%Edinburgh

India%Hook.Barnard,%National%Academy%of%Sciences

Richard%Johnson,%Global%Helix%&%BioBricks%Foundation

Linda%Kahl,%BioBricks%Foundation

Jason%Kelly,%Ginkgo%Bioworks

Steve%Laderman,%Agilent Technologies,%Inc.

Carlos%Olguin,%Autodesk

Megan%Palmer,%Synberc

Randy%Rettberg,%iGEM%Foundation

Lynn%Rothschild,%NASA

Max%Ryadnov,%National%Physical%Laboratory

Ben%Sheridan,%BSI

Reshma%Shetty,%Ginkgo%Bioworks

Christina%Smolke,%Stanford%University
August&2,&2013 Munro&S.&and&Salit&M.,&NIST9ABMS&Program Report&Page 2 of 8

Executive)Summary

The&NIST9ABMS&Workshop&to&Develop&a&Metrology&Roadmap&for&Synthetic&Biology&was&

held&at&Imperial&College, London,&United&Kingdom on&July&12,&2013&immediately&following&

the&Sixth International&Meeting&on&Synthetic&Biology&(SB&6.0). The&intention&of&this&

workshop&was to develop the&critical&components&necessary&for developing an&actionable

synthetic&biology&metrology&roadmap. The&first component is&a&prioritized&list&of essential

metrology&infrastructure&– new&measurement technologies,&reference&materials,&reference&

data,&reference&methods,&and&validated&predictive&models.&The&second component is a list&of

the biological&engineering capabilities that&will be&enabled&by&building&this metrology&

infrastructure.&An&actionable&roadmap&will&enumerate&the&developments&in&measurement&

science&and&infrastructure, and&will&identify&how&these&advances&will&improve&our&ability to&

engineer&biological&systems.

This&workshop&report&summarizes&the&observations&of the&26&workshop&participants,&a&

diverse&group&from&academic,&government,&industry,&and&non9profit&organizations.&This

report does¬&necessarily&reflect&the perspectives of&the organizations&that&the

participants represent.&Furthermore,&it&was&agreed&that&this&report&would be&shared&

broadly to&solicit&input&from synthetic&biology&stakeholders&who&could¬&be&present&at&

this&initial&meeting.

The&charge&to&the&workshop&participants&was&to&collaboratively&describe&the&

aforementioned&components&needed&for&a&synthetic&biology&metrology&roadmap.&The&

metrology&chapter&of&the International&Technology&Roadmap&for&Semiconductors&(ITRS)

was&held&up&as&model to&guide&the&discussion.&The presentation&describing&the charge&to&the&

workshop,&the&invitation&letter, and&the&agenda&are&provided&at&the&end&of&this&document.

The&top&3&identified&metrology&infrastructure&needs&were:

1. Measurement&technology&and&method development for&high9throughput&analysis&at&

the&single9cell&level,&with&the&specific&objective&of&measuring diversity&of&function&

within&a&cell&population.

2. DNA&fabrication&standards&that&will&provide&metrics beyond&cost&per&base and&error&

rate of&gene&synthesis,&such&as cost&per&variant,&turn&time,&or&validated&function

3. Standards for&comparing&performance of&engineered&biological&systems

Two&distinct,&but&linked, ways&of&assessing progress&of&the&field&and&impact&of&developing&

metrology&resources&were&identified:&

• Applied&capabilities that&are&directly&related&to&commercial&applications&of&

engineered&biological&systems&

• Foundational&capabilities that&may&or&may¬&support¤t&or&future&commercial&

applications
August&2,&2013 Munro&S.&and&Salit&M.,&NIST9ABMS&Program Report&Page 3 of 8

Both&types&of&capabilities should&be&included&in&a&comprehensive&and&actionable&metrology&

roadmap,&although&there&was¬&agreement over&the&relative&importance&of&the two

categories.

We&welcome&your&feedback&on&this&initial&report&and&we&solicit&your&suggestions&for&

concrete&actions&that&can&take&us&another&step&forward&toward building&an&actionable&

metrology&roadmap&for&synthetic&biology.

I.)Prioritizing metrology infrastructure)needs

A&non9exhaustive&list&of&potential&metrology&infrastructure&needs&was elicited&from&

workshop&participants. This&list&includes needs&for reference&materials,&data,&and&methods&

as&well&as&new&measurement&technologies.&The&diverse&group&also&discussed&sociological,&

intellectual&property,&and&procedural&considerations&for&measurement&science&needs&in&

synthetic&biology.&The&list&of&concepts&provided&by&participants&is&shown&in&Table&1&and&is&

rank9ordered&based&on&participant&votes.&Each&participant&had&an&equal&number&of&votes&

that&they&could&distribute&amongst&the&entire&list&as&desired.&Prior&to&voting&the&list&of&

concepts&were&grouped&into&the&categories,&Design,&Build,&Test,&Scale,&and&Use&and&if

participants&proposed&similar&concepts&those&concepts&were&grouped&together&for&voting.

*

It&was¬ed&that&“simulate” is&a&key&component&of&the&design9build9test&cycle. Better&

measurements will lead to&improved&simulation&capabilities&with&validated predictive&

models&and&accelerate&the&design9build9test cycle. It&was&also¬ed&that&the&list&of&

metrology&needs&is&meant&to&build&a&roadmap&for&the&synthetic&biology&community;&it&is¬&

work&that&would&be&done&solely&by&metrology&institutes&such&as&the&National&Institute&of&

Standards&and&Technology&(NIST)&or&the&National&Physical&Laboratory&(NPL).

The&highest&priority&need&was&measurement&technology&and&method development for&the&

purpose&of&characterizing&diversity&of&function&in cell&populations.&Ideally&these&

measurement&technologies&would&enable&high9throughput,&rapid,&single&cell&analysis&

techniques,&and&would&provide&the&characteristics&of&measurement&comparability

(traceability&and&measurement&uncertainty).&

The&second&and&third&most&highly&ranked&metrology&needs&were&standards&for&DNA&

fabrication&and&standards&for&comparison&of&engineered&cells.&These&standards&could&be&a&

combination&of&reference&materials,&reference&data,&and&reference&methods.&For&DNA&

fabrication&a&“SYNPACK”&benchmark&was&proposed,&similar&to&the&computing&benchmark&

LINPACK.&It&was&agreed&that¤t&metrics,&such&as&cost&per&base,&are&insufficient&and&new&

metrics&for&DNA&fabrication&such&as&cost&per&variant,&turn&time,&or functional&validation&of&

sequences&are&needed.&For&comparison&of&engineered&strains,&reference&methods&to&

quantify&small&molecule&productivity&and&yields&are&needed.&This&type&of&comparison&is&

critical&for&choosing&which&strains&will&be&best&to&scale&in&an&industrial&process.

&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&

* Reshma&Shetty&and&Sarah&Munro&organized&the&list&of&measurement&needs
August&2,&2013 Munro&S.&and&Salit&M.,&NIST9ABMS&Program Report&Page 4 of 8

Other&high&priority&needs&included&measurements&of&metabolites&(e.g.&in%vivo%biosensors),&

fundamental&processes&(e.g.&transcription)&and&cellular&resources&and&loads.&Ideally&these&

types&of&measurements&would&be&in%vivo and&transferable&– not&limited&to&a&single&class&of&

metabolites&or&a&species&of&organisms.&

II.)Identifying)biological engineering)capabilities)that)would be)

enabled)by)new)metrology)infrastructure

Participants&considered&what&improved&biological&engineering&capabilities&could&be&linked&

to&metrology&infrastructure&developments. These&were&in&two&categories, applied&

capabilities&directly&related&to¤t&commercial&applications&of&engineered&biological&

systems&and&foundational&capabilities&that&may&or&may¬&have&immediate&or&future&

commercial&impacts. There&was&tension&between&a&desire&to&focus&a&roadmap&on the&near9

term&applied&capabilities and&a&desire&to&describe&foundational&capabilities&that&may&or&may&

not&have&immediate&commercial&impacts.&Concern&was&also&expressed&that&it&may&be&too&

early&to&delineate&any&capability&indicators,&because&we&may&push&research efforts&in&the&

wrong&direction.&By limiting&scope&to¤t&synthetic&biology&industrial&applications&we&

might&miss&the&opportunity&to&foster a&phase9change&for&the industry&by&exploring&

foundational&engineering&capabilities.&Conversely&if&we&encourage impractical&and&abstract&

target&capabilities&with&unclear&applications,&we&could&hinder the&growth&of&both&the&

current, and future, synthetic&biology&industry¶digms. It&is&possible that&by&

acknowledging&these&issues&and&considering&both&types&of&capabilities&in&a&metrology&

roadmap&for&synthetic&biology&we&can&avoid&these&potential&pitfalls.

Biological&engineering&capabilities&that&could&be&enumerated&and&quantified&in&a&metrology&

roadmap&include:

• Achieving&commercially&viable&synthetic&biology&production&methods for&chemical&

intermediates,&e.g.&top&12&biomass9derived&intermediates&identified&in&2004&DOE&

report.

1 Important&metrics&to&consider&for&comparison&with&non9biological&methods&

for&deriving&these&chemical&intermediates&include achieving economic&parity&(or&

better),&as&well&as land&use&and&environmental&footprint.

• Expansion&to&novel&material&science&and&biomedical&applications beyond&the&

existing&small&molecule&and&pharmaceutical&markets,&such&as&links&between&

biological&materials&and&electronics,&identifying&and&producing&new&natural&products&

for&medical&applications,&or&cell9based&therapeutics.

• A&“phase9change” in the&breadth&and&scale&of&the&synthetic&biology&industry

o Expansion&of&the&types&of&organisms&that&can&be&engineered,&beyond&the&

small&cohort&of¤tly&used&organisms

&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&

1 Werpy, T., Petersen, G., Aden, A., et al. (2004). Top Value Added Chemicals From Biomass. Volume 1-Results of 

Screening for Potential Candidates From Sugars and Synthesis Gas, 76. Retrieved from 

http://oai.dtic.mil/oai/oai?verb=getRecord&metadataPrefix=html&identifier=ADA436528
August&2,&2013 Munro&S.&and&Salit&M.,&NIST9ABMS&Program Report&Page 5 of 8

o Movement&from&large9scale¢ralized&production&toward&distributed&

production

• DNA&synthesis&capabilities – how&much,&how&fast,&how&accurate?

• Efficiency&of&DNA&integration&into&an engineered&biological&system

• Precision of&expression&control

• Number&of&orthogonal®ulatory&elements

• Number&of&input&channels/computational&scale/output&channels

• How&long&does&it&take&to&build&a genetic&program?

• Evolvability/Mutation&robustness – control&of&mutation&rates&would&have&

implications&for&biosafety&and&industrial&scale&production

• Control&of&population&diversity – applications in&control of&the&humanµbiome

and&environmental&engineering,&etc.

Conclusion

During&this&initial&workshop&participants&worked&to&develop&two&critical&components&of&a&

metrology roadmap&for&synthetic&biology;&prioritizing&metrology&infrastructure&needs&and&

identifying&biological&engineering&capabilities&that&would&be&enabled&by&new&metrology&

infrastructure.&Input&from&the&broader&synthetic&biology&community&is&requested.&We&solicit&

both&your&suggestions&for&further&refinement&of the&content&of&this&report&and&specific&

actions&that&would&bring us&closer&to developing a metrology&roadmap.
August&2,&2013 Munro&S.&and&Salit&M.,&NIST9ABMS&Program Report&Page 6 of 8

Table&1. Identified&and&prioritized&measurement&needs from&participants

Type Measurement%Need Votes

Test

Representations&for&genetic&(function)&diversity&(population&

composition&and&evolution&thereof)

11

HT&+&single&cell&measurements&that&can&scale

Turn9key&non9invasive&imaging&and&tracking&of&large&#s&of&single&cells

High9throughput&single&cell&measurements&of&protein&or&other&

chemical&concentrations

Establish&comparability&for&flow&cytometry

High&throughput&‘omics,&preferably&single&cell

Direct&noninvasive&rapid&single9cell&quantitative&measurements&of&

RNA,&protein&and&metabolites

Build

“SynPack”&– DNA&Fab&benchmarks,&$,&time,&accuracy (analogue&to&

LINPACK&benchmarks&for&computing)

10

Standards&for&assessing&the&performance&of&gene&synthesis&beyond&

cost&per&bp&and&error&rate

Cost&per&rational&junction

Cost&per&variant&– how&to&account&for&level&of&diversity

Turn&time

Scale

Comparable&methods&for&measurement&of&strain&productivity&&&yield&

for&small&molecules 8 Standards&for&measuring&and&benchmarking&the&performance&of&

strains&that&make&small&molecules

Test

Direct&measure&of&RNA&pol&along&DNA&in&live&cells

Standard&unit&of&gene&expression&– like&a&kg&or&meter,&perhaps&several& 7

to&compare&against&different&chassis&– E.%coli,&yeast,&mouse

Test

Rapid,&quantitative&measurement&of&novel&metabolites&(when&don’t&

know&exact&chemical&structure)

6 Genetically&encoded&sensors&to&all&primary&and&secondary&

metabolites,

Biosensors&for&in&vivo&monitoring&and&sensing&of&many&kinds&and&

multiplexed

Test Measurement&for&the&load&a&construct&places&on&a&cell 5 Measurement&for&maximum&available&cellular&resources

Use Incentives&to&adopt&metrology&and&standards& 4

Test

Standard&breadboard&system&that&scales&complexity

3

Standard&cell9free&solution&for&characterization

Need&standard&environment&for&measurement,&just&like&STP

Unpack&black&box&of&expression

Measure&each&step,&single&molecule&under&known&conditions,&[NTP],&

temp,&linear&or&circular&DNA,&binding,&initiation,°radation
August&2,&2013 Munro&S.&and&Salit&M.,&NIST9ABMS&Program Report&Page 7 of 8

Type Measurement%Need Votes

Design

Use

Reliable&methods/tools&for&checking&IP&status&of&biological&

components&and&designs

Standards&for&disclosure&of patents&that&cover&(“read&on”)&standards& 3

adopted&or&being&considered&for&adoption&by&the&SB&research&

community

Build

Test

Standard&open&vector&backbone&library,&standard&starter&kit&of&pre9

instrumented&organism 3

Test Gene&expression&reference&objects&covering&top&5&operational&

variables 3

Use

Safety&&&efficacy&measurements&for&deliberate&environmental&release&

of&organisms 3 Characterization&of&environmental&effects/functions&including&and&

beyond&organismal&fitness,&gene&flow

Design

Definitions&of&terms&in&synthetic&biology,&i.e.&what&is&a&part,&etc.

Ontological&framework&and&characterization&data&for&gene&functions& 3

(that&go&way&beyond&species&origin,&if&any)

Design Data&types&for&part&characterization& 2

Design Design&rules&and&associated&data&and&measurements& 2

Use

Metrology&for&assessing&the&biosafety&level&of&parts&&&devices&&&genes&

(regulatory&science)&

Standard&function9level&classification&of&virulence&pathogenicity&at& 1

the&genetic&function&level,&so&we&don’t&do&risk/safety&screening&based&

on&species&origin&alone

Use

Standard&for&“best&practice&in&responsible&innovation”

Best&practice&for&incorporating&consumer/user&needs&into&upstream& 1

design&

Use Measurements&to&bridge&+&link&academic/company&– for9profit&

divides 1

Use The&‘meaning’&of&biological&information&needs&to&be&agreed +&

understood and&also&machine&readable 1

Use Can&we&define&Shannon&Entropy&of&biological&systems?&If¬&can&we&

define&the&biological&equivalent/analogue&for&the&Shannon&Entropy& 1

Use Evolvable&standards&– our&understanding&of&biology&is¬&fixed −

Design Characterization&DNA&“Commons”:&Units,&methods,&

interoperable/shared,&reference&materials/data&sheets −

Design

Need&standard&genetic&background

Standard&strain&use:&in&vitro&work&is&very&valuable,&but&much&work& −

will&remain&in&vivo&(in&which&case&correct&strains&need&to&be&used)

Test “Stimulate&–>&Response”&test&methodologies&at&the&single&cell&level,&

multi9cell&level −
August&2,&2013 Munro&S.&and&Salit&M.,&NIST9ABMS&Program Report&Page 8 of 8

Type Measurement%Need Votes

Test Measurement&of&toxicity&a&construct&places&on&a&cell −

Scale Set&of&standard&fermentation&conditions −

Set&of&standard&feedstock,&medium&formulations

Use

What&would&be&the&end&product&i.e.&reference&methodology&versus&

reference&materials?

9 Is&the&priority&to&have&intercomparison&studies?&Would&useful&

reference&materials&be&molecules&(genes,&proteins)&or&sources&(cell&

lines)?

−

Test Automation&– so&we&can&collect&very&large&amounts&of&data, only&with&

enough&data&may&we&get&to&a&good&level&of&understanding −

Test Reference&methods&for analysis,&calibration,&&&controls,&e.g.&removing&

background&auto9fluorescence&– large&variations&with&strain −
Charge'to'Workshop'Presenta0on'

1"

NIST/ABMS"Workshop"to"

Develop"a"Metrology"Roadmap"

for"Synthe?c"Biology"

CoChosted"by"

Imperial"College"London"

BioBricks"Founda?on"

Na?onal"Academy"of"Sciences"

Who"are"we?"
Charge'to'Workshop'Presenta0on'

2"

Na?onal"Ins?tute"of"Standards"and"

Technology" • U.S."Na?onal"

Measurement"Ins?tute"

– U.S."Department"of"

Commerce"

– Advance"“measurement""

science,"standards,""

and"technology”"

– NonCregulatory"

• 6"research"laboratories"

Advances"in"Biomedical""

Measurement"Science"“ABMS”"Project"

Founding"Affiliates:"
Charge'to'Workshop'Presenta0on'

3"

Worldview"

Systema?c"approach"that"

lets"me"know"how"

confident"I"can"be"in"the"

results;"when"I"know"how"

confident"I"can"be,"I"can"

make"good"decisions."

• Traceability"

• Measurement"

Uncertainty"

• Method"Valida?on"

CHARGE'TO'THE'WORKSHOP'
Charge'to'Workshop'Presenta0on'

4"

We"could"be"wrong"about"all"of"

this."

Disclaimer"

Takeaways"

• Consensus"“Canonical”"

Engineering"Process"

– organizing"tool"for"

communica?on"

– framework"for"iden?fying"

metrology"needs"

• List"of"Metrology"Needs"

– current,"exis?ng"

measurements"that"need..."

• characteriza?on"

• improvements"

• comparability"

– new"measurements"

• things"we"can’t"measure"today"

that"we"need"

• Possible"SB"Engineering"

Performance"Parameters"

– Complexity"of"a"refactored"

gene?c"program?"

– Size"of"a"perfect"synthe?c"

DNA"object?"

– Turn"?me"for"design,"build"

and"test"of"a"new"design?"

– How"many"designs"can"be"

cycled"in"parallel?"

– How"many"DCBCT"cycles"

before"something"works?"

– How"reusable"is"a"gene?c"

object/program/module?"

• Considera?on"of"Prac0ces'
Charge'to'Workshop'Presenta0on'

5"

ITRS"Metrology"Roadmap"

one'chapter'in'a'larger'technology'roadmap

THE INTERNATIONAL TECHNOLOGY ROADMAP FOR SEMICONDUCTORS: 2011

INTERNATIONAL 

TECHNOLOGY ROADMAP 

FOR 

SEMICONDUCTORS

2011 EDITION

METROLOGY

THE ITRS IS DEVISED AND INTENDED FOR TECHNOLOGY ASSESSMENT ONLY AND IS WITHOUT REGARD TO ANY 

COMMERCIAL CONSIDERATIONS PERTAINING TO INDIVIDUAL PRODUCTS OR EQUIPMENT.

THE INTERNATIONAL TECHNOLOGY ROADMAP FOR SEMICONDUCTORS: 2011

TABLE OF CONTENTS

Metrology ..............................................................................................................................1

1. Introduction and Scope......................................................................................................... 1

1.1. Introduction.....................................................................................................................................1

1.2. Scope .............................................................................................................................................2

1.3. Infrastructure Needs.......................................................................................................................3

2. Difficult Challenges............................................................................................................... 3

2.1. Difficult Challenges.........................................................................................................................3

3. Microscopy ........................................................................................................................... 4

4. Lithography Metrology .......................................................................................................... 6

4.1. Line Roughness..............................................................................................................................8

4.2. Measurement Uncertainty ..............................................................................................................9

4.3. Explanation Of Uncertainty In Tables Met3 And Met4 .................................................................11

5. Front End Processes Metrology.......................................................................................... 12

5.1. Starting Materials..........................................................................................................................13

5.2. Surface preparation......................................................................................................................13

5.3. Thermal/thin films .........................................................................................................................13

5.4. Strained Si processes ..................................................................................................................14

5.5. FERAM .........................................................................................................................................15

5.6. Doping technology........................................................................................................................16

6. 3D Interconnect Metrology.................................................................................................. 17

6.1. Bonding Overlay...........................................................................................................................18

6.2. Bonded Interface Void Detection..................................................................................................18

6.3. Bonded Interface Defect Identification .........................................................................................19

6.4. Bonded Interface Defect Review..................................................................................................19

6.5. Edge Bevel Defects......................................................................................................................19

6.6. Bond Strength Uniformity .............................................................................................................19

6.7. Bonded Wafer Pair Thickness......................................................................................................20

6.8. TSV Etch Depth............................................................................................................................20

6.9. TSV Etch Profile ...........................................................................................................................20

6.10. TSV Liner, Barrier, Seed Thickness.............................................................................................20

6.11. TSV voids .....................................................................................................................................20

6.12. Shape and Stress.........................................................................................................................21

6.13. 3D Metrology for Copper nail and Pillars .....................................................................................21

7. Interconnect Metrology ....................................................................................................... 21

7.1. CU-LOW κ Metallization Issues and Metrology Needs ................................................................22

7.2. Low κ Dielectrics Issues And Metrology Needs ...........................................................................23

8. Materials And Contamination Characterization................................................................... 24

8.1. Materials and Contamination in Strain-Based Devices ................................................................26

9. Metrology for Emerging Research Materials and Devices................................................... 27

9.1. Update on Advances in Graphene Metrology ..............................................................................28

9.2. Update on Advances in Memristor Metrology ..............................................................................28

9.3. Comment on the Impact of Nanoscale Dimensions on Metrology ...............................................28

9.4. 3D Atomic Imaging and Spectroscopy .........................................................................................29

9.5. Other Microscopy Needs including Scanning Probe Microscopy ................................................30

9.6. Optical Properties of Nanomaterials.............................................................................................31

9.7. Electrical Characterization for Emerging Materials and Devices .................................................31

10. Reference Materials........................................................................................................ 31

11. Reference Measurement System.................................................................................... 32

12. References ..................................................................................................................... 34

Detailed"measurement""

needs"and"projec?ons..."
Charge'to'Workshop'Presenta0on'

6"

Semiconductor"Fab""

Technology"Requirements"

What"are"the"SB"Performance"Parameters?"

(Technology'Requirements)"

• How"do"they"evolve?"

– what"new"applica?ons"

do"the"evolved"

parameters"enable?"

• What"metrology"needs"

to"happen"to"enable"

this"evolu?on?"
Charge'to'Workshop'Presenta0on'

7"

Shape"of"the"day"

• Opening"remarks,"charge"to"the"

workshop""

• Synthe?c"biology"(SB)"engineering"

processes"

• Consensus"SB"engineering"process"

• Iden?fy"measurement"strengths"&"

gaps"

• Priori?ze"list"of"measurement"gaps"

• How"should"we"quan?fy"our"ability"to"

engineer"biology?"

– What'does'success'look'like?'

• "Working" discussion" – What'would'an'ideal'SB'engineering'

process'look'like?

• Close"the"Loop"

– How'will'new'metrology'impact'our'

ability'to'engineer'biology?

SB"Engineering"Process"

• describing"the"

engineering"process"for"

SB"in"consensus,"generic"

way..."

– will"let"us"iden?fy"design"

rules"

– will"let"us"talk"about"

what"measurements"are"

needed"at"what"point"in"

the"process,"and"what"

difference"they’ll"make."
Charge'to'Workshop'Presenta0on'

8"

What"does"an"SB"Engineering"Process"

look"like?"

• Process"diagram"of"how"you"would"get"to"crea?ng"a"product"via"

synthe?c"biology"

• You"could"be"abstract"or"use"an"exis?ng"product"or"something"

novel""

– Coat"made"by"bacteria"that"consists"of"cellulose"

• What"are"the"steps"(and"cycles)"that"are"needed"to"get"there?"

• Don't"worry"too"much"about"it"being"ar?s?c,"you"could"just"use"text"

instead."

• What"is"common"across"different"types"of"industrial"SB"processes?"

• Converge"to"a"consensus"model"

• Then"we"can"iden?fy"measurements"and"standards"that"we"need"to"

create"to"enable"the"industry"to"grow."

Probio?c"for"gut"

microbiome

related"disease"

Create"

gene?c"

designs"to"

achieve"

func?on"

Understanding"of"

crosstalk"with"the"

na?ve"genome"

Build"system"

with"the"new"

gene?c"design"

ScaleCup"

C Size"limits"

C ?me"scales"

C separa?on"

processes"

Databases"of"

gene?c"designs"

with"reliable"

func?ons"

Predic?on"of"strain"fitness,"

produc?vity,"?tre,"yield"

Product"distribu?on"

C Homogeneity,"stability,"

viability,""

C Feedstock"availability"

C Quality"control"

Consumer"use"

C “Safety"and"Efficacy”"

C"Regula?on"

C Social"issues"for"

adop?on"

Implement"and"

test"design"in"

system""

intraC"and"interCcell"

“engineering"

controls”"C"efflux"

pumps,"energy"

balance"

Interac?ons"of"the"probio?c"with"

environment,"e.g."human"gut,"

affects"on"any"other"species"
Workshop(Invitation(Email

Dear!colleagues,

There!have!been!numerous!calls!to!develop!metrology!for!synthetic!biology!–

infrastructure!such!as!new!measurement!technologies,!reference!materials,!reference!data,!

reference!methods,!and!validated!predictive!models.!We!invite!you!to!join us!for!an!

informal,!invitation>only!workshop!to!identify!and!prioritize!metrology!needs.!The!

workshop!will!be!held!following!SB6.0!at!Imperial!College,!London,!UK!on!Friday!July!12,!

2013!from!8:00am!– 2:00!pm.

The!intended!outcome!of!this!workshop!is!an!actionable!metrology!roadmap!– a!set!of!goals!

for!metrology!resources!in!synthetic!biology.!This!roadmap!should!detail!how!meeting!

these!goals!will!improve!our!ability!to!engineer!biology.!To!ensure!an!effective!and!targeted!

discussion!we!request!that!each!participant!present!one!slide!describing!their!vision!of!the!

process!of!engineering!a!biological!system!for!a!commercial!application.!Please!expand!

upon!the!design>build>test!paradigm!to!describe!additional!critical!steps!needed!to!create!a!

commercially!viable!synthetic!biology!product!or!technology,!such!as!scaling!production!or!

product!distribution.!By!integrating!your!diverse!and!valuable!perspectives!to!describe!a!

consensus!synthetic!biology!enterprise!process!model!we!can!begin!to!identify!the!gaps!

and the!most!needed!metrology!infrastructure.

We!hope!you!can!join!us!in!what!we!believe!is!a!critical!step!toward!growing!our!global!

bioeconomy!– building!a!synthetic!biology!metrology!roadmap.!If!you!cannot!attend!please!

feel!free!to!suggest!a!different!participant!from!your!organization!for!us!to!invite!to!this!

workshop.!Please!RSVP!at!your!earliest!convenience!and!email!your!slide!to!

sarah.munro@nist.gov by!July!3,!2013.

Best!regards,

Marc!Salit,!Ph.D.!and!Sarah!A.!Munro,!Ph.D.

Biosystems!and!Biomaterials!Division

National!Institute!of!Standards!and!Technology

Advances!in!Biomedical!Measurement!Science!Program

Stanford!University
Workshop(Agenda

NIST%ABMS)Workshop)to)Develop)a)Metrology)Roadmap for)Synthetic)Biology

Co>hosted!by

National!Academy!of!Sciences

BioBricks!Foundation

Imperial!College!London

Sherfield!Hall,!SALC!6

Friday!July!12,!2013!

08:00!AM!– 02:00!PM

08:00!– 08:30 Opening!remarks!and!charge!to!the!workshop

08:30!– 09:30 Participants!present!their!typical!synthetic!biology!(SB)!engineering!

processes

09:30!– 09:50 Break

09:50!– 10:30 Derive!consensus!SB!engineering!process

10:30!– 11:00 Use!consensus!process!as!a!framework!to!identify!measurement!

strengths!&!gaps

11:00!– 11:15 Prioritize!list!of!measurement!gaps

11:15!– 12:00 How!should!we!quantify!our!ability!to!engineer!biology?

What(does(success(look(like?

12:00!– 01:00 Working!lunch!discussion

What(would(an(ideal(SB(engineering(process(look(like?

01:00!– 02:00 Close!the!Loop

How(will(new(metrology(impact(our(ability(to(engineer(biology?