Echo Acoustic Liquid Handling for Genomics Research
EMPOWERING GENOMICS RESEARCH WITH ASSAY MINIATURIZATIONGenomics Research
BROCHURE
Version 1.0 | AUGUST 2017

LABCYTE INC.
170 Rose Orchard Way
San Jose, CA 95134
USAToll-free: +1 877 742−6548 | Fax: +1 408 747−2010BROCHURE | ECHO FOR GENOMICS RESEARCH

Echo Acoustic Liquid Handling Technology
Echo acoustic liquid handling technology
revolutionizes scientific research by using
sound energy to provide highly accurate, fully
automated, non-contact dispensing of fluids.
By utilizing the unique Dynamic Fluid Analysis™
technology by Labcyte, the Echo systemdetermines fluid composition, fluid height, andthe power needed to eject a precise volumeof fluid into the destination well. This analysis(instrument model dependent)

happens in milliseconds, enabling precise andaccurate transfer of nanoliter (nL) droplets into
an inverted microplate. Larger volume transfers
are achieved by rapidly transferring several
hundred droplets per second.
Transfers can be made from any well to any well,allowing for miniaturization and automation ofcomplex assays to dramatically reduce reagent
costs and save precious samples.

FIGURE 1: The Echo system transducer rapidly moves between wells on the source plate while thedestination plate also moves, allowing rapid transfer from any well to any well for multiple fluid types.

The attractiveness of the instrument was its extreme
flexibility. You can transfer from any well to any well,in any combination, extremely fast, and also withextremely low volumes.
– Andy WattIonis Pharmaceuticals

Labcyte offers different models of the Echo® Liquid Handler to meet customer volume andthroughput needs. For genomics applications, we recommend using the Echo® 525 LiquidHandler, the first rapid acoustic liquid handler designed specifically for biochemical andgenomics reagent transfer. The Echo 525 Liquid Handler provides rapid transfers from25 nL to 5 μL per well. With its versatile fluid range, transfer volume range, any well to any
well transfer capability, and powerful applications software, the Echo 525 Liquid Handler
supports a wide range of genomics workflows.

Echo® 525 LIQUID HANDLER2

Impacts on Genomics ResearchUp to 100x Reduction in Assay VolumeSince introducing the Echo Liquid Handler in 2004, we have continued to help our customers attain better scientific data while reducing costs andwaste in a wide range of applications. In 2012, with the introduction of the Echo 525 Liquid Handler, we were able to quickly extend those benefits
to genomics research. Echo Liquid Handlers overcome traditional barriers in genomics by dramatically reducing sample and reagent volume
requirements. While miniaturization reduces research costs, the Echo system's non-contact transfer also eliminates cross-contamination to ensure
reliable and reproducible data. From the basics of PCR setup to the complexities of synthetic biology, the Echo Liquid Handler saves time and money,
improves decision making, and empowers research programs.

Impact of Miniaturizationin Genomics Research Applications
Application

Cost per Reaction(as recommended)

Miniaturized
Cost per Reaction

Gibson / Golden Gate DNA Assembly$15.90

$0.16

100x

NGS Library Prep

$72.91

$0.73

100x

Sanger Sequencing

$0.26

$0.06

4x

MDA Setup$17.64$4.41

4xSmartSeq 4 Setup$112.00$22.00

5x

$0.27

$0.05

6x

PCR / qPCRVolume Reduction(up to...)3

BROCHURE | ECHO FOR GENOMICS RESEARCH

Echo Liquid Handlers for Synthetic Biology
Miniaturize and Accelerate DNA Assembly and QC
for Gene Synthesis
Traditional DNA assembly methods require reactions of 10–20 microliters per well. The
Echo Liquid Handler can reduce the volume up to 100-fold, drastically cutting reagent
costs. With the ability to reliably transfer volumes as low as 25 nanoliters, Echo systems canextend the useful life of a primer library and eliminate the need to dilute high-concentration
primers, saving on storage and primer costs and preventing dilution errors. Market-leading
synthetic biology companies use Echo Liquid Handlers to automate gene synthesis withhigher throughput and lower cost than they could with tip-based liquid handlers.

We were able to successfully downscale PCRs andthe popular one-pot DNA assembly methods, Golden
Gate and Gibson assemblies, from the microliter to thenanoliter scale with high assembly efficiency, which
effectively cut the reagent cost by 20- to 100-fold.
We envision that acoustic dispensing will become
an instrumental technology in synthetic biology, inparticular in the era of DNA foundries.1For more information, visit

www.labcyte.com/synbio– Paulina Kanigowska, et al.

Reduce Costs with Miniaturization

JALA 2015£1.50300

£1.00

200

£0.50

100

£0.00

050 nL250 nL500 nL

1,000 nL

20,000 nL

Gibson Assembly
Reaction Volume

£1.80

70

£1.35

53

£0.9035

£0.45

18

£0.00

050 nL250 nL500 nL

1,000 nL

7,500 nL

Golden Gate Assembly
Reaction Volume
Manual Control

Manual Control

FIGURE 2: Cost-effectiveness and assembly efficiency comparison of different reaction volumes. Panel A: Gibson assembly. Panel B: Golden Gate assembly.1

4

Assembly Efficiency (CFU/mL,x103)

400

Reagent Costs (£)£2.00

Assembly Efficiency (CFU/mL,x103)

Reagent Costs (£)

of Gibson and Golden Gate Assembly Methods

Save 15 Hours on Your Synthetic Biology Workflow

A Comparison to the Traditional Liquid Handling Approach

speDi

g

18hours

Assembly + Pool / Normalize

Pool/Func

t ionalT
est int
Norm

CellzealiTra
nsfecQCnrary
PLibTransformatiolyAssemb

Traditional LIQUID HANDLER

nse

6 hours
rep

12 hourslT
estin

sehoursnctiona

Assembly + Pool / Normalize

FuCellDi

spenctzealirm
Nol/3.2

PooTra
n

sfe

QC

rep
yP
rar
Lib

at
io
rm
sfo
Tranlymb
Asseg

12 minsn

3 hours

The Echo system can rapidly pool oligos or DNA fragments from library plates. Since there is no contact withthe fluid and no time spent changing or washing tips, the Echo system can transfer each oligo or fragmentfrom any well of a microplate in less than a second. This can save 15 hours in a high-throughput setting.
Echo® 525 LIQUID HANDLER

Furthermore, since the Echo 525 system has the ability to transfer volumes as low as 25 nanoliters, highconcentration libraries do not have to be diluted prior to transfer, resulting in simultaneous normalization while
pooling. This enables equal distribution of reads to every sample and very even representation of all samples.
This greatly reduces the time to normalize and pool libraries and improves the reliability of the entire library
preparation process.
Echo Liquid Handlers integrated into an Access™ Workstation provide a high-throughput, fully automatedsystem for pooling oligos, assembling constructs, and spotting colonies. Whether using the Gibson Assembly®
or Golden Gate cloning method, tipless acoustic liquid handling reduces costs, waste, and saves time.

[The Echo] is an extremely fast instrument... a significant savings in terms of time. We’ve beenable to compress pipelines that take about 12 hours to about 3 hours.
– Dr. Sunil Chandran
Amyris Biotechnologies

5BROCHURE | ECHO FOR GENOMICS RESEARCH

Echo Liquid Handlers for Sequencing
Low Cost, Highly Efficient Library Preparation
Echo Liquid Handlers enable library preparation in low microliter volumes for a range ofsequencing methods. Echo systems dramatically reduce reagent costs, save samples, andeliminate steps, all while improving library quality and throughput.
With Sanger sequencing, BigDye® reagent costs can be a limiting factor. Sequencing
volumes can be reduced from 10 μL to 2.5 μL using the Echo Liquid Handler for a 4-fold
reduction in cost per reaction.
16S rRNA sequencing has long been the method of choice for microbiome researchers.
The Echo Liquid Handler allows for miniaturized 16S rRNA sequencing, and NGS reagent
cost reduction also enables researchers to shift to miniaturized shotgun sequencing.

For more information, visit

www.labcyte.com/sequencing

Comparison of NGS Library Prep Costs
Description

Manual Pipetting

Echo® Liquid Handler

Amount of DNA

50 ng

0.06 – 2.0 ng

DNA volume (rxn)

25 μL

200 nL

Library prep volume (rxn)

25 μL

300 nL

Total volume

50 μL

0.5 μL

Reactions per kit

Cost per reaction

969600$72.91$0.73

We use the [Echo system] because
it allows us to perform complex
assays in very high throughput,
but also allows us to miniaturize
those assays and keep costs down.
– Dr. Chris Bakal
The Institute of Cancer Research

When NGS sequencing programs scale, the cost of library preparation

These benefits can be realized with sample preparation kits including

is a limiting factor. Using the Echo Liquid Handler for NGS library

Illumina Nextera®/Nextera® XT, KAPA HyperPlus, NEBNext® Ultra™ II,

preparation versus conventional liquid handlers enables reactionNuGEN Ovation®, and others. This low-volume transfer ability also

volumes to be reduced by up to 100-fold, dramatically reducing studymeans that high-concentration libraries do not have to be diluted

reagent costs.2 With the Echo Liquid Handler's low-volume acoustic

prior to transfer, resulting in simultaneous normalization while pooling.

transfer capability, researchers can significantly increase the number ofThis enables equal distribution of reads to every sample and evenlibraries generated while maintaining current budgets.

representation across all samples.

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Echo Liquid Handlers for Single-Cell Genomics
Low-Volume Sequencing Libraries from Single Cells
Amplification of DNA from a single cell is inherently susceptible to contamination.
Exogenous DNA from tips or nozzles used during the transfer of samples or reagents intoa PCR reaction cannot be resolved even with UV-radiation steps prior to transfer. The Echo
Liquid Handler's non-contact acoustic transfer completely avoids contact with any DNA
to substantially lower contamination risk. Furthermore, the precision and accuracy of thetransfer at lower nanoliter volumes eliminates repeat experiments, further reducing reagent
costs.
Echo Liquid Handlers miniaturize library preparation for whole genome and transcriptome
analysis of genetic material from single cells. With precise, accurate, non-contact transfers,
Echo systems can reduce multiple displacement amplification (MDA) and RNA-seq
reactions by 75% or more. Libraries for sequencing RNA or DNA can be reduced to 10 µL orless.
For more information, visit

www.labcyte.com/single-cell-genomics[The Echo 550] allows acoustic
dispensing of minute volumes
and rapid setup of low-volume
MDA reactions, while limiting theopportunity for introduction ofDNA contamination and reducing
tip waste. Reducing the reaction
volumes also decreases the costsof MDA reagents.3

Impact of Miniaturization on MDA Reaction Cost
Description

QIAGEN REPLI-gEcho® Liquid Handler

Cell material

4.0 μL1.0 μL

Denaturization buffer

3.0 μL0.75 μL

Stop solution

3.0 μL0.75 μL

Master mix

40 μL

10 μL

Total volume50 μL

12.5 μL

Tip cost$0.60–$17.64$4.41

Cost per reaction– Christian Rinke, et al.
Nature Protocols 2014

Using the Echo 525, a scale-down by 50–100x can be achieved with minor modifications of theprotocol, leading to significant cost reduction without sacrificing data quality. Furthermore, we
demonstrate the superiority of contact-free liquid transfers in molecular biology applications
with regard to reproducibility and contamination prevention.
– Dr. Stephan Lorenz
Wellcome Trust Sanger Institute7

BROCHURE | ECHO FOR GENOMICS RESEARCH

Echo Liquid Handlers for qPCR
Cost Effective, High-Throughput RT-qPCR
To avoid the impacts of poor liquid handling performance, researchers traditionally use
larger volumes of samples and reagents to prepare qPCR assays, keeping costs high andlowering throughput. Echo Liquid Handlers enable miniaturization with reaction volumes
as low as 250 nL, which reduces costs, facilitates higher throughput, and eliminates crosscontamination.
Additionally, precise and accurate transfer of sub-microliter volumes enables the additionof concentrated reagents without prior dilution. With options for integrated plate handling
automation and software tailored for genomic research, Echo systems can easily scale forproduction environments.

Comparison of Genotyping Data and Cross-Contamination
Traditional vs. Acoustic Droplet Ejection Liquid Handling
For more information, visit

FAM

www.labcyte.com/qpcr

A1.000E+11.000E+11.000E+1
1.000E+1Traditional
Traditional

1.000
1.000

RFU
RFU

RFU
RFU

1.000
1.000

1.000E-1
1.000E-1

1.000E-2
1.000E-2

Our findings demonstrate thata single [Echo] system replaces
8–10 traditional liquid handlingrobots while increasing quality andreproducibility.4

1.000E-3
1.000E-3

1515

2525

3535

CyclesCycles1515

1.000E+11.000E+13535

ADE
ADE

1.000
1.000

RFU
RFU

RFU
RFU

2525

CyclesCycles

VIC

TraditionalTraditional

1.000
1.000– Carol Cain-Hom, et al.

1.000E-1
1.000E-1

1.000E-2
1.000E-2

1.000E-3
1.000E-3

1.000E+1
1.000E+1ADE
ADE

1.000E-1
1.000E-1

1.000E-1
1.000E-1

J Lab Automation 2016
1.000E-2
1.000E-2

1.000E-2
1.000E-2

1.000E-3
1.000E-3

1.000E-3
1.000E-3

1515

2525

3535

1515

2525

CyclesCycles

4.5
4.5B
VIC (ApoB) RFU
VIC(ApoB) RFU

FIGURE 3: Comparison of quantitative PCR (qPCR)based
genotyping
data
quality
byplatform.
Amplification curves (A) and cluster plots (B) aredepicted for both traditional- and acoustic droplet
ejection (ADE)-assembled reactions. (A) Curves areillustrated for FAM (top) and VIC (bottom) channels;
the green line shows the Cq threshold (0.4). (B) The
same data are interpreted as a cluster plot. Black Xs
are no-template controls (NTCs), green dots represent
experimental samples, and red dots (highlighted by ablue circle) denote ambiguous data samples that cannot
be clearly assigned a genotype.4

4.5
4.5

Traditional
Traditional

2.5
2.5

0.2
0.2
11ADEADE2.5
2.577
FAM
FAM(Rosa26)(Rosa26)RFU
RFU

83535

CyclesCycles14140.2
0.2
1177
FAM
FAM(Rosa26)(Rosa26)RFU
RFU1414

Access™ Laboratory Workstation for Genomics Research
Out-of-the-Box Automation for Echo Liquid Handlers
Combine the revolutionary performance of the Echo Liquid Handler with automated plate handling and integrated devices to create walk-awaysystems tailored for a range of genomic applications. With the Access Workstation, Echo Liquid Handlers can be easily incorporated into an
integrated system to automate genomic workflows including, but not limited to, qPCR, PCR, enzyme reactions, DNA/RNA quantification, sample
pooling, and normalization.

Typical Devices Used in a Genomics Configuration• Labcyte Echo 525 and/or 550/555 Liquid Handler
For more information, visit

www.labcyte.com/access-workstation• BMG FLUOstar Multimode Reader• Agilent Technologies PlateLoc Sealer• Agilent Technologies Microplate Centrifuge• Brooks Automation XPeel Peeler• Roche LightCycler 480 or 1536
• Inheco ODTC 384 or 96 Thermal Cycler• Mecour Thermal Tower

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BROCHURE | ECHO FOR GENOMICS RESEARCH

Echo® Software Applications for Genomics Research
Quick and Reliable Liquid Handling Task Management
Labcyte has a suite of Echo® Software Applications to assist researchers in creating liquid handling protocols for specific applications. Eachapplication is designed around a specific liquid handling workflow and uses a combination of wizards and graphical interfaces to simplify the creationof plate formats, liquid transfer routines, and output files. Researchers can quickly create a variety of protocols off-line for the Echo Liquid Handler
and use built-in simulators to validate every transfer before running live. The suite of Echo software applications enables the Echo Liquid Handler toquickly and efficiently accomplish any liquid handling task. For genomics workflows Echo® Cherry Pick guides file-driven transfers from any well to
any well, and Echo® Plate Reformat enables the design of custom layouts used to assemble assays or reformat and replicate screening libraries.

Echo® Cherry PickEcho® Plate Reformat

Echo Cherry Pick software uses information

Echo Plate Reformat software offers a variety

in pick lists to transfer from any sourceof transfer functions to design custom layouts.

well to any destination well, for pooling

Resulting protocols can be used to assemble

oligos for gene synthesis or libraries forassays for NGS library prep, synthetic biology,sequencing.

gene expression, or genotyping.

For more information, visit

For more information, visit

www.labcyte.com/echo-cherry-pick

www.labcyte.com/echo-plate-reformat

File-driven transfers from any well to any well

Design, develop, and assemble assays

10Echo® Qualified Consumables for Genomics ResearchEcho® Qualified Source Microplates

Echo® Qualified Reservoir

Echo® Qualified 384-well Source Microplates ensure precise, accurate

The Echo Qualified Reservoir microplate enables convenient assay

liquid transfers, delivering the best possible results in miniaturized

assembly and efficient large reagent volume transfers, with the ability toassays. Echo Qualified Source Microplates are deionized and are

dispense up to 2.55 mL per well.

packaged in anti-static bags to ensure precise drop placement.
Microplates are available with low dead volume, custom barcode, tissue
culture-treated, or sterile options.
For more information, visit

For more information, visit

www.labcyte.com/echo-qualified-source-plateswww.labcyte.com/echo-qualified-reservoir

Labcyte Service and Support
Maximize Your Instrument Performance
Timely service and preventive maintenance are essential for optimal instrument
performance and data quality. Labcyte offers a range of service contract options for
the Echo Liquid Handler and Access Laboratory Workstation to fit every lab’s needs
and budget. Labcyte provides global field service and applications support with local
personnel in the United States, United Kingdom, continental Europe, Australia, andAsia. Our application scientists have extensive experience with genomics workflows
and provide support and training on all Labcyte products to help you maximize theutility of the Echo Liquid Handler and Access Laboratory Workstations.
For more information, visit

www.labcyte.com/labcyte-support

REFERENCES
1 Smart DNA Fabrication Using Sound Waves: Applying Acoustic Dispensing Technologies to Synthetic Biology. Kanigowska et al., JALA, 2015.
2 Low-Cost, High-throughput Sequencing of DNA Assemblies Using a Highly Multiplexed Nextera Process. Shapland et al., ACS Synth. Biol., 2015.
3 Obtaining Genomes from Uncultivated Environmental Microorganisms Using FACS–based Single-cell Genomics. Rinke et al., Nature Protocols, 2014.
4 Mammalian Genotyping Using Acoustic Droplet Ejection for Enhanced Data Reproducibility, Superior Throughput, and Minimized Cross-Contamination.
Cain-Hom et al., J Lab Automation, 2016.

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© 2017 LABCYTE INC. All rights reserved. Labcyte®, Echo®, MicroClime®, the Labcyte logo, Access™, andDynamic Fluid Analysis™ are registered trademarks or trademarks of Labcyte Inc., in the U.S. and/or other countries.
FOR RESEARCH USE ONLY. Not for use in diagnostic procedures.

BRH-GENO-1.0
AUG 2017