Why Automation is Integral to the EU-OPENSCREEN Compound Collection
App Note / Case Study
Published: July 3, 2025

Credit: Hamilton
EU-OPENSCREEN supports a growing network of research sites with a shared chemical compound collection essential for high-throughput screening and early drug discovery.
Handling over 100,000 compounds and generating millions of aliquots required a shift to automation. EU-OPENSCREEN needed a solution that could integrate diverse instruments, maintain sample stability and support remote, reproducible operations across Europe.
This case study highlights how EU-OPENSCREEN implemented a fully automated workflow for compound dissolution, aliquoting, storage and plate reformatting, meeting the scale and speed of modern screening demands.
Download this case study to discover:
- How automation accelerated compound distribution to 30+ partner sites
- How 13 components were integrated into a single, unified system
- Insights into building flexible, scalable compound management workflows
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CASE STUDY EU-OPENSCREEN COMPOUND HANDLING & DRUG SCREENING
Summary
EU-OPENSCREEN’s compound storage and management
facility stores and distributes copies of an extensive chemical
compound collection to its partner sites. In order to perform
this task, the facility is equipped with an automated, integrated
system consisting of thirteen instruments, including a Hamilton
Verso® Compound Management System and two Hamilton
Microlab® STAR(let) liquid handlers. The full system is controlled
by the Hamilton VENUS® software, and the instruments’
positions are physically reached via the HMotion Robotic
Arm. In this Case Study, we describe how this system is used
to produce over 1.5 million compound aliquots of the EUOPENSCREEN Compound Collection for High-Throughput
Screening (HTS) studies at EU-OPENSCREEN partner sites.
About EU-OPENSCREEN ERIC
EU-OPENSCREEN is a not-for-profit European Research
Infrastructure Consortium (ERIC) for chemical biology and
early drug discovery, established in 2018. The consortium
supports all stages of a chemical tool development project,
including assay adaptation, HTS, and chemical optimization of
the resulting ‘hit’ compounds. Moreover, it operates an openaccess database and a unique, common compound collection
of over 100,000 compounds (EU-OPENSCREEN: Compound
Collections).
Dr. Philip Gribbon, General Director of EU-OPENSCREEN
commented: “EU-OPENSCREEN is committed to enhancing
Europe’s global standing in both scientific research and
economic development. Our services provide crucial data that
helps to identify and discard false positives from screening
processes, enabling the selection of promising compounds for
further refinement. This process ensures that outcomes from
screening campaigns are robust, consistent, and comparable,
thereby contributing to the establishment of high standards in
early-stage drug discovery and preclinical research.”
As an organization dedicated to advancing research and drug
development in Europe, EU-OPENSCREEN operates as a
distributed research infrastructure, which today counts more
than 30 partner sites across Europe (Figure 1).
Compound Handling at EU-OPENSCREEN
The EU-OPENSCREEN compound storage and management
facility is located at the headquarters in Berlin-Buch, Germany,
and currently has 16 employees. This facility is in charge of
supplying compounds to all partner sites. David Garcia
Lopez, current Head of Compound Management at EUOPENSCREEN, commented: “Our main job is to maintain our
compound collection and provide screening sites with copies
of this collection in high-throughput formats, such as 384-well
and 1536-well plates. This task demands extensive automation
to achieve very high throughput, while ensuring compound
stability and traceability.”
Authors: : Edgar Specker1
, David Garcia Lopez1
*, Victoria Mora1
, Sophie Masin1
, Thomas Zacher², Karim Benyaa2
,
Carolina Elejalde3
, Gabriela Boza-Moran3
*
1 EU-OPENSCREEN ERIC, Robert-Rössle-Str. 10, Building C87, D-13125 Berlin Germany
² Hamilton Germany GmbH, Lochhamer Schlag 11, DE-82166 Gräfelfing, Germany
3
Hamilton Bonaduz AG (Robotics), Via Crusch 8, 7402 Bonaduz, Switzerland
* for correspondence: david.garcia.lopez@eu-openscreen.eu and mboza-moran@hamilton.ch
Automating Compound Handling to Enable HighThroughput Screening of the EU-OPENSCREEN
Compound Collection Across Europe
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Compound Handling Automation
To satisfy the requirements for throughput, flexibility, and
reliability of the Compound Management facility at EUOPENSCREEN, a highly-integrated automated system was
designed and implemented. Dr. Edgar Specker, former
Head of Compound Management at EU-OPENSCREEN,
commented: “Given that compound management involves
many tasks such as storing, capping/decapping, plate
sealing/peeling and liquid transfer, we were looking for
automation solutions that allowed us to easily integrate
multiple devices. Moreover, we were looking for vendors with
an established reputation that could offer us the support we
needed to achieve the required level of complexity. Hamilton
emerged as the ideal partner”.
System Overview
The automated system for compound handling consists of
a Hamilton Verso® M2 Compound Management System,
integrated via an HMotion Robotic Arm with a Hamilton
Microlab® STAR™ and Microlab® STARlet liquid handler,
a LabElite® Integrated I.D. Capper, and a centrifuge, a
LiCONiC LPX880 Plate Hotel, a Beckman Coulter Echo 650
Acoustic liquid handler, an Azenta’s Life Sciences IntelliXCap
deCapper, automated Plate Seal Remover (formerly XPeel),
and Ziath DP5 Mirage Rack Reader, a LVL fully-automatic
SAFE Capper/DeCapper and an Agilent PlateLoc Thermal
Microplate Sealer. In total, 13 instruments are integrated into
this automated system (Figure 2).
Mr. Karim Benyaa, the Hamilton Robotics International
Project Leader in charge of this project, explained how these
instruments communicate with each other: “Over the last
fifteen years, Hamilton has gathered much experience when
it comes to integrating third-party devices and developing
complex automated workflows. We have also developed a
communication strategy for the easy integration of our liquid
handlers into other complex systems, together with integrator
companies. In the case of EU-OPENSCREEN, the largest and
most complex instruments controlling the complete process
are Hamilton systems. One of the major advantages is the
direct communication of VENUS®, Hamilton’s automated
liquid handling software, with INSTINCT® S, Hamilton’s
automated sample management software. For the integration
of all the other instruments (i.e. third-party devices), we
developed customized drivers and integrated them into
Hamilton VENUS® software, which functions as the central
hub.”
Services provided by EU-OPENSCREEN:
• HTS of in-house/open-access compound collection, using dedicated established or on-demand bioassays
• Screening of proprietary compounds against a wide range of biological assays to identify new biological activities
and novel potential applications
• Development of chemical probes and lead compounds
• Optimization of ‘hits’ or candidates
• Publication of all compound structures and large-scale open-access screening data in EU-OPENSCREEN’s openaccess European Chemical Biology Database (ECBD) (https://ecbd.eu)
• Training on topics such as assay development, assay technologies, instrumentation and automation, compound
management, and informatics
• Finding and securing grants with partners
• Establishment and maintenance of collaborations with industrial partners
Learn more about EU-OPENSCREEN services here: www.eu-openscreen.eu/index.html
Figure 1. Network of EU-OPENSCREEN Partner Sites. Green:
Full member country; Light Green: Observer country.
www.eu-openscreen.eu/about/partner-sites.html
Figure 2. System Overview. (1) Hamilton Verso® M2 Compound Management System, (2) LVL fully-automatic SAFE Capper/DeCapper,
(3) Space for additional stacked devices, (4) Hamilton HMotion Robotic Arm, (5) LiCONiC LPX880 Plate Hotel, (6) Hamilton Microlab®
STAR liquid handler, (7) Azenta’s Life Sciences Ziath DP5 Mirage Rack Reader (8) Agilent PlateLoc Thermal Microplate Sealer, (9) Hamilton
Centrifuge, (10) Azenta’s Life Sciences Automated Plate Seal Remover, (11) Azenta’s Life Sciences IntelliXCap DeCapper, (12) Beckman
Coulter Echo 650 Acoustic liquid handler, (13) Hamilton LabElite® Integrated I.D. Capper, and (14) Hamilton Microlab® STARlet liquid
handler.
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3
4
5
6
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10 8
11
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Hamilton Compound Storage Overview
The Verso® M2 at EU-OPENSCREEN is a 3.8 by 2.2 meter
-20 °C storage system. It consists of one aisle with one tray
shuttle, a universal picker, an Input/Output module, a handoff module, a video recording system with three cameras,
a 1D and a 2D Barcode Reader, and an active thawing
module (Figure 3). Samples can be (un)loaded manually via
the front Input/Output module, in addition to the automatic
(un)loading via the rear hand-off module. The Verso® handles
a wide range of labware types, including tubes, vials, and
plates.
Hamilton Liquid Handlers Overview
The Hamilton Microlab® STAR™ system has eight 1000 µl
pipetting channels, a CO-RE® 96 Multi-Probe Head, a
CO-RE® Gripper Tool (for on-deck transports), and a variety
of plate and tip positions (Figure 4). The Microlab® STARlet
has four 1000 µL pipetting channels, two 5000 µL pipetting
channels, a CO-RE® 384 Multi-Probe Head, a CO-RE®
Gripper Tool, four Hamilton Heater Shakers, one 1D Barcode
Reader, and a variety of plate and tip positions. Moreover,
the LabElite® Integrated I.D. Capper, next to the Microlab®
STARlet, is equipped with a Linear Transfer Unit (i.e., a rail),
Tube Picker (inside of
the Verso®)
Active Thawing /
(manual) Input/Output
Module
Rear Hand-off Module (for integration)
2D Barcode Scanning (inside of
the Verso®)
Sample Storage (inside of the
Verso®)
Picker Window
(Viewing and Service)
Helpful Definitions
Method: A series of steps programmed to run
sequentially and uninterrupted, designed to perform a
specific task or process.
Workflow: A structured set of methods, whose
sequence can vary to accomplish a broader or more
complex objective.
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which can bring plates directly from the LabElite® position
for decapping and scanning to a “deck pipetting position”
(Figure 5).
Both systems can use Nested Tip Racks (NTRs), which
allow tip stacking to increase the number of tips on the
deck without compromising the deck space. Before tips are
picked up, they are transported to a designated “tip pickup position” via the CO-RE® Gripper Tool. The STARlet also
uses conventional tips in frame racks.
Description of the Automated Methods
Currently, ten automated methods are integrated into the
system, each using different combinations of instruments:
1. Compound dissolution and aliquoting
2. Compounds (un)loading to/from -20 °C storage
3. Compound reformatting (96-Tube Racks to 384-Well
Plates)
4. Plate Stamping
5. Plate Replication
6. Cherry Picking
7. Quality Control for liquid transfer
8. Sample Prep for LC-MS
9. Serial Dilutions
10. Compound reformatting (384 to 1536-Well Plates)
Dr. Specker commented: “The methods were implemented
such that we could start them individually whenever needed.
The Verso® is used in method 2, the Microlab® STAR™ in
methods 3 and 8, and the Microlab® STARlet + LabElite®
Decapper in methods 1 and 10. The Echo is used in methods
4 to 7.” The main methods involved in the preparation of
the copies of the EU-OPENSCREEN compound collection
provided to all partner sites are the first three: Compound
dissolution and aliquoting, compounds (un)loading to/from
-20 °C storage, and compound reformatting (96-Tube Racks
to 384-Well Plates) (Figure 6).
Dr. Specker explained the first two methods for compound
dissolution and aliquoting in detail:
“The EU-OPENSCREEN Compound Collection contains
different sublibraries ranging from commercial and
structurally diverse compound sets, fragments, bioactive
compounds, and constantly growing academic compound
collections (https://ecbd.eu). Most of the EU-OPENSCREEN
Compound Collection is sourced from commercial vendors
(> 100,000 compounds). The commercial compounds are
provided as pre-dissolved in DMSO at 10 mM concentration
and delivered in 96-Tube Racks (LVL SAFE® 2D Tubes and
Racks). The academic compounds, on the other hand,
Figure 3. Overview of Verso® M2 Compound Management System at EU-OPENSCREEN.
are received as powder and are first added and weighed
in 24-tube racks (Micronic’s 6.00ml Screw Cap Tubes) by
the chemist before being sent to the EU-OPENSCREEN
team. Once the compounds arrive, they are dissolved
and aliquoted in the same type of 96-Tube Racks as the
commercial compounds, using the automated system. For
this, the system PC, via the VENUS® software, is supplied
with a .CSV file containing the barcodes of the 24- and
96-Tube Racks, the individual tube positions, and the
dispensing volumes for each compound to create a 10 mM
DMSO solution.
The 24-Tube Racks are then manually loaded into the
STARlet + LabElite® system, which scans barcodes, removes
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3
5
4
6
7
8
9
Figure 4: Deck Layout of the Hamilton Microlab® STAR™ System at EU-OPENSCREEN. (1) 4X Deep-Well Plate positions, (2) Active
Nest (special position for holding plates requiring piercing or very precise special dispensing like 1536-Well Plates in position), (3) 2X Carriers
for Microtiter Plates, (4) 4X Tip pick-up position for the 96-MPH, (5) Tip Park position (for reusing tips), (6) 4X 50µl NTR Carriers, (7) 96-MultiProbe Head, (8) CO-RE® Gripper, (9) Tip Waste Channel.
1
2 4 5
6 7 8 9 10 11
Figure 5: Deck Layout of the Hamilton Microlab® STARlet + LabElite® System at EU-OPENSCREEN. (1) LabElite® DeCapper, (2) Orbit
1D Barcode Reader, (3) Deck Pipetting position, (4) Active Nest, (5) Carrier with 5X 1 mL tip positions, (6) Carrier with 3X Microtiter Plate
positions (at the back) and 2X Deep-Well Plate positions (at the front) (7) 5 mL Linear Tip Carrier, (8) Trough Carrier (200 mL), (9) 4X Hamilton
Heater Shakers, (10) CO-RE® Gripper, (11) Tip Waste for single channels.
3
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the tube caps, and dispenses the required amount of DMSO
into each tube. After recapping the 24-Tube Racks, they are
shaken and incubated for 1 hour on the on-deck Hamilton
Heater Shakers (HHS) to ensure the compounds dissolve
properly. The tubes are subsequently decapped, and
1 mL of the 10 mM DMSO solution is transferred into two
identical 96-Tube Racks (Figure 7). After this, the 24-racks
are recapped using the LabElite® system, manually unloaded
and stored in standard freezers at -20 °C. The 96-racks
are manually unloaded, recapped with a SAFE® CAP
96 CHANNEL XT Decapper (SAFE® 96 XT Version-Fully
Automatic 96-Channel Capper/Decapper), and stored on the
Verso® Store at -20 °C via the Input/Output (IO) module”.
Before loading the samples into the Verso®, the Verso®
database is updated with a .CVS data file generated by the
VENUS® software and edited with the KNIME® software
(www.knime.com), in order to add more information to the
sample barcodes (e.g., volumes and sample/EOS IDs).
During loading, the Verso® scans the samples and relays all
the information to the Verso® database.
When the compounds are requested by the partner sites,
these are unloaded from the -20 °C storage and reformatted
into 384-Well Plates. Mr. Benyaa explained these methods
in detail:
“First, the system PC is supplied with a .CVS file containing
the barcodes of the tubes to be requested from the Verso®.
This information is relayed to the Verso®’s INSTINCT® S
software, allowing the Verso® to pick the requested tubes,
sort them into racks, and place them on the hand-off
slide, where the HMotion Robotic Arm picks them up and
transports them to the Plate Hotel.
The barcodes and positions of the tubes, rack barcodes,
and volumes are pulled from the Verso®’s database and
combined with the plate barcodes and requested dispensing
volumes, using a customized KNIME® workflow. The
resulting .CSV file is then used as input for the reformatting
process, which is controlled by the VENUS® software on the
STAR™ system PC.
-20°C STORAGE
UNLOADING
COMPOUND
REFORMATTING
-20°C STORAGE
LOADING
-20°C STORAGE
LOADING
COMP. DISSOLUTION
& ALIQUOTING
ML STARlet
ACADEMIC COMPOUNDS
24-Tube Racks
Powder
ACADEMIC COMPOUNDS
96-Tube Racks
10mM in DMSO
ALL COMPOUNDS
96-Tube Racks
10mM in DMSO
ALL COMPOUNDS
96-Tube Racks
10mM in DMSO
SELECTED COMPOUNDS
384-well Plates
10mM in DMSO
SELECTED COMPOUNDS
384-well Plates
10mM in DMSO
EU-OPENSCREEN
SCREENING SITES
-20°C -20°C
COMMERCIAL COMPOUNDS -20°C
96-Tube Racks
10mM in DMSO
LabElite® I.D.
Capper
ML STAR
Verso® Verso M2 ® M2 Verso® M2
H-Motion
LiCONiC LPX880
Plate Hotel
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Figure 6: Overview of the main methods involved in the preparation of copies of the EU-OPENSCREEN Compound Collection
provided to EU-OPENSCREEN partner sites. For more information, see Figure 9
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384-well Target Plate 1-12
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Figure 7: Transfer Pattern of the compound dissolution and
aliquoting (Method 1). The solid compounds in four 24-Well Tube
Racks are dissolved and aliquoted in two 96-Well Tube Racks.
During reformatting, the Plate Hotel first unloads the 384-Well
Plates (Echo® Qualified 384-Well Polypropylene Microplate
and Echo® Qualified 384-Well Cyclic Olefin Copolymer
(COC) Source Microplate, Low Dead Volume), which are
transported to the Microlab® STAR™ deck via the HMotion
before unloading the requested tubes. Once the racks with
the requested tubes are picked up, the HMotion transports
them to the scanner and the decapper, which read the 2D
barcodes of the tubes and removes their caps, respectively,
before transporting them to the Microlab® STAR™ deck.
Once everything is on the liquid handler, the compounds are
transferred according to the user instructions from the tubes
to the 384-Well Plates via the 96 Multi-Probe-Head (MPH)
(Figure 8).
After the liquid transfer, the HMotion picks up the tubes,
which are recapped before being returned to the Plate
Hotel. This process repeats for up to four racks to fill the
384-Well Target Plates. As soon as all target plates are
filled, the HMotion transports them to the sealer and then
to the Plate Hotel. The subsequent transport to the Verso®
and the relay of information (including the compound liquid
levels) from the system PC to the Verso® database is done
automatically”.
A detailed workflow of the three methods involved in the
preparation of copies of EU-OPENSCREEN Compound
Collection provided to partner sites is shown in Figure 9.
Figure 8: Transfer pattern of the compound reformatting from 96-Tube Racks to 384-Well Plates (Method 3)
Verso® picks the
requested Tubes
and sort them
into Racks
Input: CSV-File
with 2D Barcode
and Volume
information
Input: CSV-File
with Source/
Target Rack and
Tube Barcode,
and Volume
information
Plate Hotel unloads the Target
384-well Plates
Manual loading
of the 96-tube
Racks into the
Verso®
Transfer of requested
volumes from Source
Tubes to Target Plates
using the 96MPH**
The Plates are
placed on the
STAR’s deck
Plate Hotel
unloads the
Source 96-tube
Rack
Barcode
Scanner reads
the Tubes’ 2D
Barcodes
Sealer seales
the Target Plates
Decapper caps
the Tubes
The Source
96-tube Rack
is placed on the
STAR’s deck
LabElite®
re-opens
24-tube Racks
VENUS®
generates an
output file with
all relevant data
Decapper
decaps the
Tubes
Plate Hotel
stores the Target
Plates
Plate Hotel
stores the
Source 96-tube
Rack
Input: CSV-File
with 2D Barcode
information
Input: CSV-File
with 2D Barcode,
Sample/EOS
ID and Volume
information
Input: CSV-File
with 1D Rack- &
2D-Tube Barcode
information
STARlet transfers
1 mL of the dissolved
compounds into
96-tube Racks
LabElite® closes
the 24-tube
Racks
VENUS® generates
an Output File with
Barcode and Position
information
STARlet scans
1D Barcodes of
24- and 96-tube
Racks
Manual loading of
24-capped and
96-uncapped
tubes Racks into
the STARlet
96-tube Racks
are unloaded
and capped
manually
LabElite® scans
2D Barcodes
and opens 24-
tube Racks
STARlet transfers
DMSO into tubes
to generate
10 mM solutions
LabElite® closes
24-tube Racks
STARlet HHS*
incubates and
shakes the
Racks
Verso® places
Racks on Handoff position
Plate Hotel
stores the Racks
KNIME® Software
generates Input
File with Tubes &
Racks Barcode,
and Volume
information
-20°C STORAGE
UNLOADING
COMP. DISSOLUTION
& ALIQUOTING
COMPOUND REFORMATTING -20°C STORAGE
LOADING
-20°C STORAGE
LOADING
User Input Hamilton Instruments Software Third-Party Instruments (Integrated)
Verso® opens
the empty
Hand-off
position
Plate Hotel
unloads the
Racks
Verso® closes
the loaded
Hand-off and
scans barcodes
Verso® scans the
Racks Barcodes
and stores them
Verso® stores
scanned racks
and logs data in
the database
Verso® logs data
in the database
KNIME® software
edits Output file
to include sample
information
* HHS - Hamilton Heater Shaker
** MPH - Multi-Probe Head
Figure 9: Detailed workflow of the main methods involved in the preparation of copies of the EU-OPENSCREEN Compound
Collection provided to EU-OPENSCREEN partner sites.
KNIME edits output
file to include
sample information
Benefits of the Automated System
Throughput
The automated system was developed with the purpose of
supplying all screening sites with copies of the compound
collection hosted at the EU-OPENSCREEN headquarters
(over 100,000 compounds). Mr. Lopez commented: “The
automated methods have been a success. Within 1.5 years,
we have been able to send over 1.5 million compound
aliquots to our partner sites, consisting of about 300 plates
per compound collection copy. Without this automated
system, it would have never been achievable. Moreover,
thanks to our automated storage system, we are able to
securely store, trace, and retrieve our complete compound
collection with very little hands-on interaction.”
Flexibility and Integrability
In addition to the method for reformatting compounds from
96-Tube Racks to 384-Well Plates, nine other methods have
been developed within the same integrated system. This
flexibility is provided in big part, thanks to the ability to operate
most of the instruments via the Hamilton VENUS® software.
Dr. Specker commented: “The integration of all systems was
a challenge we identified from the beginning, and the ability
of Hamilton to provide us with a solid solution was a decisive
factor in our vendor selection criteria. The team presented
us with a very comprehensive concept of the system and
accompanied us throughout the method implementation
phase, even though it was COVID-19 time, and there were
many changing regulations and uncertainties. Moreover, the
ability to integrate a large, automated sample management
system with the rest of the automation ecosystem was a
unique proposition”.
Sample Traceability
One of the key benefits of an integrated system, such as
the one implemented at EU-OPENSCREEN, is that samples
are always traced along the workflows, which provides full
assurance of the identity of what is pipetted. Mr. Benyaa
commented: “The samples’ barcodes are read by the
Verso®, the decapper and the STAR, allowing reliable
handling. Moreover, we added a feature to the VENUS®
software that automatically updates the volume left in the
compound vials after pipetting into plates. This helps during
later liquid transfers with the 96-Multi Probe Head, as the
Microlab® STAR™ knows exactly the lowest liquid level in
the tubes of a 96-Tube Rack and starts to aspirate from
this height. This prevents pipetting errors and incorrectly
aspirated volumes.” (Figure 10)
KNIME generates
Input File with Tubes
& Racks Barcode,
and Volume
information
VENUS® saves
the new liquid level
of each compound
Verso® logs data
into the database
Verso® logs data
into the database
-20°C STORAGE
UNLOADING
COMPOUND
REFORMATTING
-20°C STORAGE
LOADING
-20°C STORAGE
LOADING
Input: CSV-File
with Source/
Target Rack and
Tube Barcode,
and Volume
information
COMP. DISSOLUTION
& ALIQUOTING
VENUS® generates
an output file with
Barcode and Position
information
Figure 10: Transfer of information between the user, the system PC (running the VENUS® software), and the Verso® database.
“We are very pleased with the flexibility of our integrated
automated system, the quality of the Hamilton
instruments, and the support of the Hamilton Team.
We continue developing new methods to automate
more tasks, and we envision adding more instruments
to the current setup. In fact, we recently added a HJBioanalytik HJ@Sealer a few weeks ago.
Moreover and as part of our training mandate, we
plan to collaborate with Hamilton to create material
and organize guided tours to educate people about
automation and compound handling,” said Mr. Lopez.
| 9
©2024 Hamilton Bonaduz AG. All rights reserved.
Disclaimer: throughout this Case Study, protected product names may be used without being specifically marked as such.
Web: hamiltoncompany.com/automated-liquid-handling
Hamilton Bonaduz AG
Europe HQ
Tel: +41 58 610 10 10
Hamilton Company
United States HQ
Tel: +1 775 858 3000
United Kingdom &
Ireland
Tel: +44 121 272 92 80
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