The Latest Applications in
Automated Liquid Handling
From sample preparation to cell culture and antibody
engineering, automated liquid handling is improving
accuracy, efficiency, and reproducibility across lab workflows
STRATEGIES
for Enhancing Workflow
Efficiency
AUTOMATING
Cell Culture and Antibody
Engineering
INCREASING
Accuracy and Reproducibility
in Assays
AUTOMATED
LIQUID HANDLING
RESOURCE GUIDE
2 Lab Manager Automated Liquid Handling Resource Guide
Table of Contents
Transforming Workflows with Automated Liquid Handling ..3
Key Benefits of Automated Liquid Handling .....................4
Lab Staff Thrive Using Automation Tools................................ 5
Simplifying Lab Tasks with Automated Liquid Handling............. 7
Three Simple and Proven Automation Protocols for
Serial Dilutions on the ASSIST PLUS Pipetting Robot................. 9
Choosing an Automated Liquid
Handler for Your Lab.......................................................13
Key Applications for Automated Liquid Handlers............14
Automated Liquid Handling: Keeping Antibody
Engineering Consistent ....................................................15
Automating Cell Culture for Therapeutic
Monoclonal Antibody Development ...................................17
Automated Set-Up of the Lonza PyroGene®
Recombinant Factor C (rFC) Assay for Endotoxin
Detection on the ASSIST PLUS .......................................... 20
Assays and Automation in Robotic Workstations................... 25
The Benefits of Automated Liquid Handling for
Microscale Samples ...................................................... 27
Successfully Maintaining Automated Liquid Handlers.............. 30
3 Lab Manager Automated Liquid Handling Resource Guide Introduction
Transforming Workflows
with Automated
Liquid Handling
Enhancing efficiency, accuracy, and innovation with automation
The adoption of automated liquid handling systems is transforming lab workflows, enhancing
efficiency, precision, and reproducibility across numerous applications. As sample processing
demands increase, automation can alleviate lab personnel of repetitive tasks and allow scientists
to focus on higher-value activities. Automated liquid handlers (ALHs) can streamline sample
preparation, high-throughput screening, and complex assay development in labs of all sizes, from
small research-focused labs to large pharmaceutical companies.
This resource guide explores the numerous benefits, applications, and
considerations involved in implementing an ALH. Chapter one contains a discussion
of the key advantages of automation, from improving productivity to reducing
errors. The second chapter explores specific applications of ALHs, including
antibody engineering, cell culture automation, and high-precision assays. The guide
also includes best practices for selecting, maintaining, and optimizing automated
platforms to ensure their longevity and reliability. As labs face growing demand
for faster results without sacrificing accuracy and precision, understanding the
complexities of automated liquid handling can help lab leaders implement the best
solutions to stay ahead in an increasingly competitive landscape.
Chapter One
Key Benefits
of Automated
Liquid Handling
Labs face increasing pressure to deliver results faster while maintaining accuracy and
cost-efficiency. Automated liquid handling is emerging as a critical solution to these
challenges, as it offers precision, speed, and enhanced reproducibility in workflows. In
reducing reliance on manual pipetting, automated systems free skilled personnel to focus
on data interpretation, problem-solving, and other high-value tasks rather than repetitive
tasks. Despite its advantages, some lab staff may express concerns over job displacement
and the complexity of these technologies. However, when properly integrated, automation can be complementary to human expertise.
This chapter explores the key benefits of automated liquid handling, including its role in
increasing productivity, enhancing accuracy, and optimizing resource allocation. We also
discuss how lab managers can foster a culture of innovation by educating staff on the advantages of automation and its ability to create more engaging work environments. Lastly,
we outline important considerations for selecting an automated liquid handling system to
best meet your lab’s needs.
5 Lab Manager Automated Liquid Handling Resource Guide
Lab Staff Thrive Using
Automation Tools
Access to automation enables a bright future for the lab and lab staff
By Scott D. Hanton, PhD
All labs face the challenge of higher expectations, greater
demands on time and budgets, and pressure to deliver outcomes faster. Many labs are addressing these challenges by
adopting some form of lab automation, which enables technical work to be completed with less reliance on the hands of
the lab staff. Modern lab robots can safely and accurately deliver a wide range of lab activities, including complex sample
preparation, rapid analysis, and large designed experiments.
Once these experiments are initiated, lab staff can walk away
and complete other, higher-value activities.
Despite these contributions to the lab, automation still inspires
fear in some lab staff, which revolves around the replacement
of human staff with robots and computers. To build a vision
for how increased lab automation can improve work conditions
and success, lab managers need to educate themselves and
staff about the positive impact the adoption of these tools can
have. This education will need to address several key areas,
including an effective vision of the future, understanding the
value of lab staff, driving higher-value activities, increasing
productivity, and improving opportunity decisions.
6 Lab Manager Automated Liquid Handling Resource Guide
Effective vision of the future
One of the keys to any successful change management project
is the development of a coherent vision of the future. Lab
managers must have a defined idea of what the future lab looks
like as the first step, and then determine how lab automation
fits into that picture. This vision needs to address the benefits
for both the lab and the staff, and show people how they will
be valued contributors after lab automation is installed and
running. The vision will clarify how the technical problems
will be solved, how the automation will be implemented, and
the benefits of the work dedicated to the change.
After a vision is defined, it is important to communicate it to
staff in a variety of ways to build support and maximize its
chances of success. Communicating change requires dedication and repetition. Lab staff will need time to process and
adopt the changes in the lab. To continually reinforce the
value of the change, it will be helpful to develop a concise,
60-second elevator speech about the direction, benefits, and
value of implementing lab automation.
Understanding the value of lab staff
Lab automation is not a cure-all for challenges faced in the
lab. The robots, hardware, and software included in an automation investment can’t complete all of the important lab
functions. To be successful, labs will need to prioritize the
activities that only human staff can successfully complete.
While lab automation can be very successful in delivering a
wide range of repeatable tasks, lab staff are required to deliver the higher-order thinking for the science in the lab to be
successful. Successful lab managers will invest in automation
to make more time available for staff to deliver creativity,
technical innovation, and critical thinking. Lab staff will
need to design, set up, and evaluate the experiments turned
over to automated tools.
Instead of threatening jobs, lab automation is an investment
that can make lab roles more interesting and important. Those
automation tools will accomplish dedicated tasks faster and
with greater precision, which will require creative critical
thinking sooner and more often to keep science progressing.
Driving higher-value activities
In this era of faster delivery from the lab, most labs would
benefit from providing staff with more time to think about
science and its challenges and problems. Lab automation
provides the opportunity for many of the tedious burdens of
lab work to be delegated to machines. Once the automation
is installed and operational, lab staff can spend more time
clarifying the questions, creating better options, critically
evaluating data, converting data into information, knowledge, and insight, and making decisions about the next steps.
Labs will benefit from having more people-time applied to
these important parts of doing good science. In most labs,
the time spent on critical thinking is limited due to all of the
tasks required to execute the science and run the lab. Lab
automation can improve that situation while delivering a
highly valuable commodity to the lab staff: time to think.
Increasing productivity
Improving productivity means producing more output at an
equal cost. The key benefit of increasing lab automation isn’t
cost reduction, but better productivity. Since lab automation
works around the clock, doesn’t need breaks, doesn’t sleep,
and works straight to the end of the process, more samples
can be processed per day. However, those automated systems
need to be told what to do. By increasing the time for lab
staff to think about the science, evaluate choices, and design
better experiments, the lab can deliver better outcomes faster. That productivity will make key stakeholders happy and
provide a better financial foundation for the lab.
Improving opportunity decisions
An important benefit of lab automation is increasing walkaway time for scientists, which enables them to complete
other important tasks for the lab. When staff are completing
work in one area, another area is incomplete, meaning the
lab suffers an opportunity cost. As staff perform lab work
that could readily be completed by lab automation, the lab is
missing the opportunity for those same staff to accomplish
other, higher-value work. Opportunity cost can be monetized and used to develop effective return on investment
calculations to improve the business case for investment in
lab automation.
As more labs adopt automation, they will demonstrate the
benefits associated with letting automation do the tedious
and repetitive work, and gain the benefits of using staff time
for more critical thinking and creative work. The future is
bright for clear collaboration between human scientists and
lab automation that enables staff to ask better questions, solve
technical challenges faster, improve productivity, and free
more time for creative thought.
Simplifying Lab Tasks
with Automated
Liquid Handling
Devices simplify and economize many basic
lab processes
by Mike May, PhD
8 Lab Manager Automated Liquid Handling Resource Guide
Most scientists or lab personnel with much experience
pipetting—especially pipetting over and over—dream of
automating liquid handling. This technology can be applied
to a wide range of processes, from serial dilutions and cell
culture to high-throughput screening and the polymerase
chain reaction. Best of all, some platforms make automated
liquid handling possible in almost any lab.
Not that long ago, most automated liquid handlers (ALHs)
required lots of lab space, mountains of money, and an
expert in robotic programming. That limited the users to
large pharmaceutical companies and other organizations
with deep pockets. Now, for a few thousand dollars and a
little bench space, almost any lab can add automated liquid
handling. Still, some obstacles must be addressed.
Overcoming obstacles
Initially, a common challenge with ALHs—and lab robotics
in general—is the fine-tuning and troubleshooting process,
which takes up the bulk of development time.
Experts agree that two of the most important criteria for an
ALH are usability and reliability. Intuitive user interfaces
and redundant systems ensure correct pipetting, but these
benefits come with a series of costs, including being expensive to purchase and maintain. Conversely, not spending enough on a system can create other problems. Some
inexpensive systems for automated pipetting can take a lot of
time to set up and still generate errors in a workflow.
An array of advances
In addition to smaller and more affordable options for automated liquid handling, ease of use has been another crucial
improvement in this technology. These improvements make
these machines easier to use for non-automation specialists,
requiring minimal training and expertise.
Advances in technology from other fields can also improve
automated liquid handling. One example comes from machine vision. Here, a camera and image-processing software
control the pipettes. The machine vision can perform many
tasks, from identifying the installed pipettes, if a well of a
plate is empty, the location of plasticware on the platform,
and so on. These capabilities minimize human intervention
and setup time while increasing reliability, since the only
hardware requirement is a camera. Although adding a camera can increase the platform’s cost, such a system should be
easier to set up and less prone to errors.
To really make this technology available in more labs and
for more workflows, a platform needs to be affordable. That’s
an ongoing improvement in parts of this instrument market,
which is driving a wider range of applications, instead of
just the high-throughput screening where automated liquid
handling started.
Expanding the user base
Scientists can now choose from a variety of manufacturers in
this product area, with systems ranging in price and capacity,
and from simple benchtop tools to industrial systems. When
budget is a main concern, purchasing a used ALH may be a
good option. Some scientists have also begun using a combination of off-the-shelf and 3D-printable parts, however, this
can require some tinkering and engineering expertise.
So, there’s clearly a range of ways to implement ALHs. Plus,
this technology can improve a variety of workflows. The
solution for a lab depends on many factors, from applications
and required throughput to economics and expertise. To get
started, it probably pays to start out small and see how automation works in your lab. Jumping into too much automation
without the right preparation could be overwhelming, not
to mention a path to a mistake. So, look around, ask around,
and see what fits best for your lab.
ALH maintenance (Sachin Rawat)
Over time, wear and tear can cause accuracy
issues, such as uneven dispensing or incorrect
liquid transfer, and environmental factors like
humidity or temperature fluctuations can introduce
variability. Regular upkeep helps to avoid these
issues, ensuring the reliability and efficiency of the
system. Contamination, wear on components, and
environmental disturbances all contribute to potential
problems, but with proactive maintenance, most
issues can be avoided.
9 Lab Manager Automated Liquid Handling Resource Guide
Three Simple and Proven
Automation Protocols for Serial
Dilutions on the ASSIST PLUS
Pipetting Robot
By INTEGRA Biosciences
Introduction
Serial dilution—a reduction in concentration by dilution—is
a common approach for screening-related applications, such
as determining minimum inhibitory concentrations (MIC)
in drug discovery, calculating the most probable numbers
(MPN) in microbiology, and performing general nucleic acid
quantifications in molecular biology. Although it is a simple
technique, poor liquid handling during interdependent
dilution steps can cause error propagation and accumulation.
10 Lab Manager Automated Liquid Handling Resource Guide
Thorough mixing is therefore crucial, but this puts a lot of
strain on the thumb, which increases the risk of repetitive
strain injuries. In addition, performing serial dilutions regularly can be a time-consuming process.
This application note describes the simplest way to perform
serial dilutions using the VOYAGER adjustable tip spacing
pipette on the ASSIST PLUS pipetting robot to gain more
walk-away time. The protocols provided outline the optimal
settings to ensure reliable results when diluting analytes in
water. For further information about modifying key parameters to suit varying conditions, see INTEGRA’s comprehensive guide to performing serial dilutions.
Key benefits
• Proven serial dilution protocols, with optimal settings for
the VOYAGER on the ASSIST PLUS, guarantee uniform
pipetting and mixing
• The VOYAGER offers flexible automated serial dilutions
across various tubes and plates, as well as the ability to
switch pipette volumes seamlessly while maintaining the
same protocol
• INTEGRA’s electronic pipettes prevent thumb strain
during liquid handling steps and, together with the
ASSIST PLUS, enable risk-free handling of hazardous samples
• The ASSIST PLUS gives users additional hands-free time,
eliminating time-consuming manual procedures
• These efficient liquid handling solutions support 2-,
5-, and 10-fold serial dilutions, with dynamic mixing
volumes ensuring homogeneity of analytes
• Simplified workflows are achieved with VIALAB’s serial
dilution protocol, which includes specific mixing parameters for managing poorly soluble analytes
Overview: How to do serial dilution
with the ASSIST PLUS pipetting robot
This application note demonstrates how to perform serial
dilution of tartrazine in water with an 8 channel 125 μl VOYAGER on the ASSIST PLUS.
Experimental set-up
The ASSIST PLUS, together with the 125 μl 8 channel
VOYAGER and 125 μl sterile, filter GRIPTIPS® pipette tips,
automates complete serial dilutions in one program consisting of three steps (Figure 1):
1 Transfer diluent to target plate
2 Transfer analyte to target plate
3 Serial dilution of analyte within target plate
Figure 1: Experimental set-up for serial dilutions.
Step-by-step procedure
Figure 2: Deck set-up for performing serial dilutions. Position A: Source—dual reservoir adapter with 2x10 ml reservoirs; diluent in A1 (blue) and analyte in A2 (green).
Position B: Target—96 well flat bottom plate (pink). Position C: Empty.
Serial dilution of an analyte
The INTEGRA dual reservoir adapter, together with 2x10
ml reservoirs, is placed on deck Position A, with diluent
(blue) in A1 and analyte (green) in A2 (Figure 2). A clear 96
well flat bottom plate (pink) is placed in landscape orientation on deck Position B (Figure 2).
11 Lab Manager Automated Liquid Handling Resource Guide
Select and run one of the following VIALAB programs:
2-fold serial dilution 125_VOYAGER_2_fold_serial_dilution
5-fold serial dilution 125_VOYAGER_5_fold_serial_dilution
10-fold serial dilution 125_VOYAGER_10_fold_serial_dilution
Specific volumes are handled by the VOYAGER (Figure 3).
The diluent is transferred in multiple dispensing steps from
the reservoir (Position A – A1) into each well of the 96 well
flat bottom plate, starting with column two (Position B). To
ensure precision during plate set-up, a pre- and post-dispense of five percent of the transferred volume is used for the
10-fold serial dilution, and 10 percent for the 2- and 5-fold
serial dilutions.
Figure 3: Serial dilutions in 96 well flat bottom plates with the 125 μl VOYAGER.
Using new GRIPTIPS, the VOYAGER aspirates the highest
concentration of analyte from the reservoir (Position A –
A2) and dispenses it into the first column of the 96 well flat
bottom plate (Position B).
Without changing the GRIPTIPS, the VOYAGER begins
the serial dilution by aspirating the specific volume (Figure
3) from column one of the 96 well flat bottom plate (Position
B) and dispensing into the second column. The VOYAGER
then mixes 100, 80, or 112 µl (for 2-, 5-, and 10-fold serial
dilutions, respectively) of the analyte/diluent five times at
maximum speed (10). A blowout is performed to clear the tip
of any remaining liquid before aspirating for the following
dilution step. The procedure is repeated until column 11 is
reached, where the last aspiration is discarded along with the
GRIPTIPS. Column 12 only contains diluent, and functions
as a blank for background noise elimination.
Tips:
• Pre-wetting tips when pipetting aqueous liquids ensures
excellent accuracy and precision
• Using adjustable mixing cycles compensates for slower
mixing speeds or poorly soluble analytes
Results
The performance of the 8 channel 125 μl VOYAGER on the
ASSIST PLUS during serial dilution of 0.36 mM tartrazine
in water in 96 well flat bottom plates (Figure 4) was analyzed
at 428 nm absorbance using the Tecan Infinite® M200 PRO.
More detailed data is provided in INTEGRA’s comprehensive guide to performing serial dilutions.
Figure 4: 2-fold serial dilution of tartrazine in a 96 well flat bottom plate.
Figure 5 shows a representational, optimized calibration
curve of a 2-fold serial dilution. Automating all liquid handling steps and mixing 100 μl of each dilution (>80 percent
12 Lab Manager Automated Liquid Handling Resource Guide
GRIPTIPS volume) five times at maximum speed (10) led
to reliable results in three independent runs. Furthermore,
final values of less than one percent were calculated for the
inaccuracy and imprecision of the individual dilution steps.
Figure 5: Result of a 2-fold serial dilution of tartrazine using optimized mixing settings
on the ASSIST PLUS.
Remarks
• VIALAB software: VIALAB programs can be easily
adapted to your specific labware and protocols, such
as when partial plates are needed
• Partial plates: Programs can be adapted at any
time to accommodate varying sample numbers, giving
laboratories total flexibility to meet current and future demands
Conclusion
• Automated workflows on the ASSIST PLUS offer reproducible results and eliminate any operator influence on
serial dilutions
• INTEGRA’s electronic pipettes ensure homogeneity of
aqueous solutions with dynamic mixing of each dilution.
This is achieved by aspirating and dispensing >80 percent of the total GRIPTIPS or reaction volume, repeated
five times at speed 10.
• Understanding how to perform serial dilutions is crucial
to optimize workflows and prevent error propagation.
The automated protocols on the ASSIST PLUS provide
optimal liquid handling settings for 2-, 5-, and 10-fold
serial dilutions.
• The ASSIST PLUS has a compact footprint to enable
risk-free dilution of hazardous compounds in a biosafety
cabinet
Current workflow
What specific tasks will you automate (e.g., pipetting,
mixing, dispensing, etc.)?
What challenges do you face with your manual
processes?
How complex are your protocols? Are they amenable
to automation?
What volume ranges and precision do you require?
Logistics
What are the physical space requirements?
Will the platform integrate easily with your existing
layout and other instruments?
Is the platform compatible with your consumables?
Does the platform support open-source or third-party
software for data integration?
Budget
What is the initial cost? Are there any ongoing
maintenance costs?
What will additional capabilities or upgrades cost?
Maintenance, compliance,
and validation
What is the frequency of maintenance, and can it be
performed by laboratory staff?
Are there service contracts or warranties available?
What error detection and correction systems
are in place?
Are there built-in alarms or notifications for mistakes
or failures?
Does the platform provide logs or audit trails for quality
control and compliance (e.g., 21 CFR Part 11)?
What type of validation is required?
Throughput
How many samples do you process daily? Weekly?
Does this fluctuate?
Is it important that the platform can scale with future
increases in demand?
What is your desired turnaround time?
Accuracy and precision
What level of precision do you require (e.g., microliter
or nanoliter ranges)?
Will the platform support your specific assay types
(e.g., qPCR, ELISA, cell culture, etc.)?
How is performance validated and calibrated?
Choosing an Automated Liquid
Handler for Your Lab
Automated liquid handling platforms offer many benefits, including boosting efficiency, precision, and throughput. It is important to
consider several factors to ensure the right fit for your lab. From assessing workflow needs and system compatibility to evaluating space,
budget, and ease of use, it’s essential to ask the right questions before making an investment. The following considerations can help
guide your decision-making process.
Chapter Two
Key Applications
for Automated
Liquid Handlers
Automated liquid handling can support numerous laboratory processes, particularly in
fields that require a high degree of precision and high-throughput capabilities. From
drug discovery to genomics, these systems enable labs to perform complex protocols with
minimal variability to ensure accurate and reproducible results.
A critical application of automated liquid handling is monoclonal antibody (mAb) engineering, which requires precise liquid handling for screening, hybridoma production, and
cell culture maintenance. Automated platforms eliminate variability in liquid transfers
and improve consistency in antibody development. Automation is also valuable for cell
culture, as it creates more sterile and efficient processes, reducing contamination risks.
This chapter highlights these and other major applications of automated liquid handling
technology. It demonstrates how labs can leverage automation to enhance experimental
outcomes, scale operations, and improve overall efficiency.
Automated Liquid
Handling: Keeping
Antibody Engineering
Consistent
Many steps within mAb engineering require precise
liquid handling
by Mike May, PhD
16 Lab Manager Automated Liquid Handling Resource Guide
Monoclonal antibodies (mAbs) make up a crucial workhorse
of molecular biology, as well as a growing number of therapeutics. In a research lab, scientists use mAbs to label and
track a wide range of targets. Pharmaceutical and biotechnology companies also turn mAbs into therapeutics, including
treatments for cancer. When engineering a mAb for research
or therapeutic applications, many steps require precise liquid
handling, which can be accomplished accurately and repeatably with automated platforms.
Most labs engineer mAbs through hybridoma technology. This involves fusing an immune B cell that makes the
desired mAb and a long-lasting myeloma cell. The B cell
tends to be short-lived, which is the reason for fusing it with
a myeloma cell.
Consistency and reproducibility are critical at each step
in an antibody engineering workflow. Any variability can
reduce confidence in the results produced. It can also reduce
the efficacy and safety of mAb-based therapeutics.
Areas for automated liquid handling
In sorting blood cells for mAb production, screening for the
most effective antibody, and a variety of analytics, automated
liquid handling can be used. The platforms are designed to
perform the same actions, in the same way, every time they
are used.
That repetitive accuracy is crucial in mAb engineering,
which is usually performed in microplates at microliter volumes. In addition to consistency, automated liquid handling
is more convenient and it saves time compared to a manual
approach.
The antibody technologies facility at Monash University in
Australia focuses on generating high-affinity monoclonal
antibodies through advanced discovery techniques and antibody engineering. “The incorporation of automated liquid
handling in antibody production has been pivotal to our
success,” says manager Hayley Ramshaw.
At Monash, automating liquid handling in the engineering of
mAbs allowed the facility to manage an increased workload.
Ramshaw says that this technology allows them to handle
multiple fusions per week.
She and her colleagues can use automated liquid handling
for many processes—the fusion itself, plating of the cells
post-fusion, analysis of all samples for antibody presence,
and cell-culture techniques, including expansion of cultures
and cryopreservation of cell lines.
Easing the transition
Automating a portion of the engineering process takes less
capital investment than automating an entire workflow.
For example, a lab could start with automating the liquid
handling in next-generation sequencing used in mAb engineering.
To automate a complete engineering process, working with
an expert eases the transition. A single vendor might suggest
a system built with devices from more than one source.
In both basic and medical research, automated liquid handling provides many benefits. The improved accuracy alone
is worth the transition. Automation also speeds up a process
and allows higher throughput. In combination, automated
liquid handling can create higher volumes of consistent
mAbs, which benefits scientists and patients.
“When engineering a mAb
for research or therapeutic
applications, many steps require
precise liquid handling, which
can be accomplished accurately
and repeatably with automated
platforms.”
17 Lab Manager Automated Liquid Handling Resource Guide
Automating Cell Culture for
Therapeutic Monoclonal Antibody
Development
Advances in automation eliminate the tedious, time-consuming aspects of cell
culture and cell line development
by Michelle Dotzert, PhD
The use of monoclonal antibodies (mAbs) for cancer treatment began in 1997, when rituximab was the first mAb approved by the U.S. Food and Drug Administration (FDA) for
treatment of some forms of non-Hodgkin lymphoma. Since
then, mAb therapeutics have grown into a multibillion-dollar market. Prior to commercialization, mAb development
begins with cell culture for cell line generation. Technological advances in cell culture automation have dramatically
accelerated the development process by increasing efficiency,
consistency, and sterility.
18 Lab Manager Automated Liquid Handling Resource Guide
Predefined specificity
The hybridoma technique, first described in 1975, is still
used to develop cell lines for mAb production. Dr. David
Fox is a professor of internal medicine in the Division of
Rheumatology and the director of the Hybridoma Core
at the University of Michigan. The Core offers antibody
development services for preclinical antibody research and
investigation, using the same process involved in therapeutic
mAb development. Fox describes this process: “We receive
the antigen from the person who wishes to develop a mAb.
We then immunize mice and test the serum to determine if
the mouse is mounting an immune response. Once there is
sufficient antibody titer in the serum, the spleen is removed
to create hybridomas by fusing spleen cells with a cell line.
Supernatant [fluid] is taken from the hybridomas, and the investigator screens for the mAb of interest that will recognize
a specific antigen and is appropriate for their application.”
Humanization techniques are required for antibodies
destined for therapeutic use in humans. “Once they are
considered a therapeutic lead, these mouse antibodies must
be humanized (by genetic engineering) unless they are made
in a humanized mouse, which allows more rapid progress
to a potential drug stage,” explains Dr. Thomas Moran, a
professor of microbiology at the Icahn School of Medicine at
Mount Sinai and the director of the Center for Therapeutic
Antibody Development.
Targeting cancer
Humanization techniques have moved mAbs into the clinic,
and several are FDA-approved for use as cancer therapeutics.
mAbs are used to target and bind tumor cells expressing
cancer-specific antigens and induce cell death. Individual antibodies exhibit unique mechanisms of action. “Monoclonals
can be used directly to bind to surface proteins on cancer
cells to kill or inhibit their growth,” explains Dr. Moran.
Trastuzumab (Herceptin), for example, targets the HER2
protein on the surface of breast and stomach cells. “[They]
can work by recruiting immune elements, delivering toxins,
producing CAR-T cells, or as bispecific antibodies that
recruit T or NK cells to kill the cancer cells.” Tositumomab
is used in the treatment of some B-cell non-Hodgkin lymphomas and is an example of a monoclonal antibody used to
deliver toxins. Bispecific antibodies consist of two different
monoclonals capable of binding to separate proteins simultaneously. Blinatumomab is a bispecific T cell engager that
binds to the CD19 protein on leukemia and lymphoma cells
and CD3 proteins on T cells to direct an immune response
toward the cancerous cells. The unique targets and mechanism of action of each mAb enable a highly specific approach
to cancer treatment compared with other treatments such
as chemotherapy. As a result, they are often associated with
fewer side effects among patients.
The automation advantage
Antibody development on a small scale is often done without
automated devices. “For the scale of culture we work with,
we mainly use in vitro bioreactor flask systems,” says Elizabeth Smith, assistant director of the Core. Sterility is critical
for all cell culture applications, and smaller-scale mAb production may not require high-throughput equipment. “I like
the control that I have over the sterility of what I’m doing
when I’m handling the liquids myself,” says Smith.
However, for large-scale production of therapeutic mAbs,
automating cell culture can offer numerous advantages,
including reducing time-consuming, repetitive tasks for
laboratory staff and enhancing throughput. Automated liquid
handling systems eliminate hours spent pipetting and ensure
highly accurate volumes. Systems that offer dedicated pipette
tips for each cell line and noncontact liquid dispensing reduce the risk of cross-contamination.
Automation, by design, reduces the amount of human
interaction with cell cultures, thereby eliminating various
opportunities for contamination. Automated systems range
in capability, with sophisticated systems enabling automated
media changes, passaging, harvesting, and monitoring when
integrated with plate readers and imaging devices.
Working with an automated system has contributed to more
than just increased productivity for Dr. Moran and his
colleagues. “The traditional method was to test and then
identify the clones through a laborious replating and retest-
“Automated liquid handling systems
eliminate hours spent pipetting and
ensure highly accurate volumes.”
19 Lab Manager Automated Liquid Handling Resource Guide
ing step. Many valuable hybridomas were lost in this process.
This system is more accurate, automated, and less prone to
contamination,” he notes.
Challenges remain
While mAbs are a promising line of investigation in the search
for cancer treatments, their development is not without challenges. Cell culture contamination from chemicals, bacteria,
yeasts, viruses, and even cross-contamination with other cell
lines can have severe consequences, including destruction
of the culture and even the cell line. Practicing good aseptic
techniques and implementing automated cell culture technologies can dramatically reduce the risk of contamination.
Another methodological challenge is to “make antibodies
that bind to native molecules as they appear on the surface of cells,” says Dr. Moran. “Often, synthesized proteins
produced to simulate the real protein are not folded the
same way and antibodies made against them do not bind
effectively to the real protein.” It is extremely difficult to
predict if an antibody developed with a specific protein will
effectively recognize the protein on the cell surface. Immunogenicity also poses challenges. Genetically engineering
the antibodies to render them more human has shown some
success; however, even fully human antibodies can elicit a
negative immune reaction. Scalability, yield, and cost are
also considerations in the development of mAbs.
Given their highly specific nature, mAbs are promising
cancer therapeutics. Their development relies heavily on cell
culture techniques, which can be laborious, time consuming,
and prone to contamination. Automated cell culture technologies ensure greater accuracy and precision, reduce the
risk of contamination, and alleviate scientists of tedious and
time-consuming tasks.
20 Lab Manager Automated Liquid Handling Resource Guide
Automated Set-Up of the Lonza
PyroGene® Recombinant Factor C
(rFC) Assay for Endotoxin Detection
on the ASSIST PLUS
By INTEGRA Biosciences
Introduction
The Lonza PyroGene rFC Assay is an alternative to the
traditional limulus amebocyte lysate (LAL) assay, which is
widely used to screen for bacterial endotoxin contamination in human and animal parenteral pharmaceuticals and
medical devices. The rFC test is used in both high- and
low-throughput laboratories and, unlike the LAL assay, is
not derived from horseshoe crab blood. Setting up the test
requires preparation of 10-fold diluted standards from the
21 Lab Manager Automated Liquid Handling Resource Guide
endotoxin stock solution supplied. Standards and samples are
tested in duplicate in a 96 well plate. To check for product inhibition, positive product controls (PPCs)—samples
spiked with a known concentration of endotoxin—are tested
alongside the samples. Following the initial plating of the
standards, samples and PPCs, a 10-minute pre-incubation
is performed, during which the user prepares a working
solution consisting of the fluorogenic substrate, assay buffer,
and rFC enzyme.
This application note demonstrates that the preparation
of the standards, samples, PPCs, and blanks—and their
addition to the 96 well plate—can be easily automated on
the ASSIST PLUS pipetting robot using a D-ONE single
channel pipetting module. Addition of the working reagent
is then completed using a VOYAGER adjustable tip spacing
multichannel pipette. Automation of all the pipetting steps
reduces the opportunity for pipetting errors and ensures
assay robustness and reproducibility. The key quality
indicators in this assay are the correlation coefficient of the
standard curve and coefficient of sample variation (CV).
Key benefits
• Automated preparation of standard dilutions eliminates
pipetting errors that could invalidate entire runs
• Users can perform testing of full or partial plates by
using the D-ONE single channel pipetting module in
combination with the ASSIST PLUS
• Error-free pipetting ensures replicate samples with tight
CV values, reducing the likelihood of repeat testing
• On-screen prompts guide the user through instrument set-up
Overview: How to perform the
PyroGene rFC Assay
The PyroGene rFC Assay is a fluorogenic assay that requires
a fluorescence microplate reader—such as the PyroWave®
XM Fluorescence Reader, paired with the WinKQCL®
Endotoxin Detection & Analysis Software—to measure
endotoxin values. Prior to setting up the plate, a template
is prepared in WinKQCL software. Figure 1 shows the
WinKQCL software template that was developed for use
with the ASSIST PLUS. This template allows up to 21
samples to be tested in duplicate on one plate with paired
PPCs. It is designed to provide optimal flexibility for varying
numbers of samples, while still allowing use of an 8 channel
pipette to deliver the rFC working solution to the plate, as
described in the assay instructions for use.
Figure 1: Lonza rFC template in WinKQCL software. Red wells: standards; blue
wells: samples in duplicate (wells A3 and A4 are empty); yellow wells: PPCs tested
in duplicate.
A 0.5-300 μl D-ONE single channel pipetting module is first
used to prepare standard dilutions. Following preparation
of the standards, PPC is added to the designated wells using
repeat dispense mode. Next, standards and samples are added to the plate in duplicate according to the above template,
with samples added to both clean and PPC-spiked wells.
Once all samples are added, the plate is pre-incubated at
37 °C for 10 minutes. During the incubation, the user prepares the working reagent in an INTEGRA 10 ml SureFlo™
reagent reservoir, which is added to the plate at the end of
the pre-incubation period using a 300 μl VOYAGER 8 channel pipette on the ASSIST PLUS.
Tips:
• Use pyrogen-free certified GRIPTIPS pipette tips in
combination with SureFlo reservoirs to ensure accurate
results. 10 ml SureFlo reservoirs require a dead volume
of less than 30 μl.
• 300 μl long GRIPTIPS can access sample volumes of
below 1 ml in 13x100 mm Lonza pyrogen-free test
tubes, and will never leak or fall off
• PPCs and samples can be dispensed using repeat
dispense mode to save time and money
• Plate layout of the blank, standards, and samples in the
WinKQCL software template is designed to offer the
most flexibility for running full or partial plates
22 Lab Manager Automated Liquid Handling Resource Guide
Experimental set-up
Deck Position A: LAL water—10 ml multichannel reagent reservoir
Deck Position B: PyroGene rFC Assay plate—96 well flat
bottom plate (Corning)
Deck Position C: Standards, samples, and PPC—INTEGRA tube rack
Figure 2: Set-up of the ASSIST PLUS for assay sample and standard addition. Position
A: LAL water in 10 ml SureFlo reservoir. Position B: 96 well assay plate. Position C:
Tube rack with Lonza pyrogen-free tubes (empty, magenta), 250 μl of 20 EU/ml
endotoxin standard (green), and 1 ml of sample (blue).
1. PyroGene rFC Assay plate set-up
STEP: Standards, samples, and PPC-spiked samples are
added to the plate.
HOW TO: Pair the 0.5-300 μl D-ONE single channel
pipetting module with the ASSIST PLUS pipetting robot.
Place pyrogen-free test tubes containing 1 ml sample in the
tube rack on deck Position C (blue tubes in Figure 2). Place
three empty tubes in Positions A1-A3 within the rack. These
are used to create the standard dilutions (magenta tubes in
Figure 2). Place a tube holding 250 μl of 20 EU/ml endotoxin
standard in A4 in the rack (green tube in Figure 2). Place a
10 ml SureFlo reservoir holding LAL water on deck Position
A, and a 96 well flat bottom plate on deck Position B.
When the ‘Lonza PyroGene Assay plate set-up’ program is
started, the pipette first dispenses 900 μl of LAL water into
each of the three empty dilution tubes (Figure 3). Next, 750
μl of LAL water is dispensed into the tube holding 250 μl of
20 EU/ml endotoxin standard, creating a 5 EU/ml standard.
Following the package insert instructions, a message on the
pipette instructs the user to vortex the 5 EU/ml standard
for one minute. The ASSIST PLUS pauses for the user to
perform this step, then restarts when the user acknowledges
the message. The next standard is created by transfer of 100
μl of the 5 EU/ml standard to the adjacent tube holding 900
μl of LAL water, followed by vortexing. The remaining two
standards are created in a similar manner.
Figure 3: LAL water is dispensed by the D-ONE single channel pipetting module.
Once all the standards have been created, 10 μl of the 5 EU/
ml standard is added to each well of the plate designated
as a PPC (Figure 4). This serves as a control to monitor
for sample inhibition of endotoxin detection. Each blank,
standard, and sample is then added to the appropriate wells
in duplicate. Duplicate samples are also added to the PPC
wells, creating the 0.5 EU/ml PPC-spiked samples. When all
standards and samples have been added to the plate, the plate
is pre-incubated at 37 °C for 10 minutes.
Figure 4: PPC is added by the D-ONE single channel pipetting module.
23 Lab Manager Automated Liquid Handling Resource Guide
PyroGene rFC Assay reagent addition
STEP: Add 100 μl of working reagent to each well of the plate.
HOW TO: While the plate is pre-incubating, manually
prepare the working reagent in a 10 ml SureFlo reservoir by
combining fluorogenic substrate, rFC assay buffer, and rFC
enzyme solution in a 5:4:1 ratio. Place the working reagent in
a clean 10 ml SureFlo reservoir on deck Position A (Figure 5). Pair a 300 μl 8 channel VOYAGER pipette with the
ASSIST PLUS and exchange the D-ONE tip deck for a standard tip deck. At the end of the 10-minute pre-incubation,
place the plate on deck Position B. Initiate the VIALAB program ‘Lonza PyroGene Assay reagent addition’ to add 100
μl reagent to each well of the plate. When reagent addition
is complete, place the plate in the fluorescence microplate
reader to complete the assay.
Figure 5: Deck set-up of the ASSIST PLUS for reagent addition. Position A: working
endotoxin reagent in a 10 ml SureFlo reservoir. Position B: 96 well plate containing
pre-incubated standards and samples.
Tips:
• VIALAB programs can be adapted to accommodate different numbers of samples, providing flexibility to meet
current and future testing demands
• For simplicity, 300 μl long GRIPTIPS are used in all
steps of this assay
Assay verification
Three runs of 21 samples plus standards were set up on the
ASSIST PLUS and tested according to the PyroGene rFC
Assay instructions for use. Samples consisted of LAL water
spiked with known concentrations of endotoxin standard.
Five samples at each concentration were run on each plate,
except for the 0 EU/ml sample, which was run six times
per plate. Data analysis was performed using WinKQCL
software. Table 1 shows the concentrations of standards
and samples.
Table 1: Endotoxin concentrations of standards and spiked samples.
Results
The results are displayed in Tables 2 and 3. The standard
curve for all runs displayed good linearity, and all curves
were within the quality parameters as defined in the instructions for use (Table 2). Samples spiked with each concentration of endotoxin were detected (Figure 6). All unspiked
samples remained undetectable at <0.005 EU/ml, which is
the cut-off for acceptable endotoxin concentrations in pharmaceuticals and medical devices. All replicates of standards,
samples, and PPCs displayed a CV within the acceptable
limit of less than 25 percent (Table 3).
Table 2: Standard curve results with quality specifications for runs 1-3.
Figure 6: Distribution of results for samples spikes at endotoxin concentrations of 2.5,
0.25, and 0.0025 EU/ml.
Standards (EU/ml) Samples of LAL water spiked
with endotoxin (EU/ml)
5 2.5
0.5 0.25
0.05 0.025
0.005 0
Correlation
coefficient
(0.980 – 1.000)
Slope
(0.760 – 1.110)
Y-intercept
(2.500 – 5.000)
Run 1 1.000 0.930 4.112
Run 2 0.999 0.903 4.258
Run 3 0.998 0.909 4.267
24 Lab Manager Automated Liquid Handling Resource Guide
Table 3: Mean CV per plate for paired samples and PPCS.
Remarks
• Partial plates: The supplied VIALAB programs can be
adapted for partial plates or for running samples in
triplicate
• Run report: VIALAB programs can be started directly
from a PC connected to the ASSIST PLUS pipetting
robot. A report is automatically generated after the run,
documenting details such as start and end times, user
identification, calculated volumes, and any errors that
occurred. This offers a convenient way to fulfill regulatory requirements.
Conclusion
• The ASSIST PLUS provides an affordable, easy-to-use
automation solution for low- to medium-throughput users
of the Lonza PyroGene rFC Assay
• High-quality, reproducible results can be achieved
with the ASSIST PLUS, eliminating the risk of costly and
time-consuming retests
• The ease and flexibility of VIALAB software allows users
to customize plate layouts or set up partial plates using
the same labware defined in this application note
Mean paired
sample %CV
Mean PPC
%CV
QC fail %CV
per plate
Run 1 4.19 4.37 0
Run 2 1.84 4.03 0
Run 3 3.66 3.87 0
Overall
mean
3.23 4.09 0
25 Lab Manager Automated Liquid Handling Resource Guide
Assays and Automation in Robotic
Workstations
These technologies improve a lab’s output and save on priceless resources
By Mike May, PhD
The evolution of robotic workstations resembles that of computers. Gargantuan systems that only experts could operate
gave way to smaller and more user-friendly systems. Despite
the decreasing size and simplified use, today’s robotic workstations often outdo their predecessors, thanks to ongoing
improvements in various technologies.
A decade or so ago, automated liquid handling conjured up
images of room-size systems at pharmaceutical companies
costing hundreds of thousands of dollars and run by teams
of experts for operation and programming. Today, less than
$10,000, enough bench space for a microwave oven-size device, and some taps on a graphical user interface can get most
any scientist going with automated liquid handling. A huge
workstation handles far more samples, but that’s not needed
in most basic research labs. In fact, some scientists turn to a
do-it-yourself approach to automate processes in a lab.
Although life science and commercial labs primarily use
robotic workstations for liquid handling, that’s not the only
26 Lab Manager Automated Liquid Handling Resource Guide
process that can be automated. These platforms can also heat
or cool samples, seal multi-well plates, and more.
When it comes to the basic reasons to automate a workstation, most scientists know that this technology can improve
a lab’s efficiency. Plus, reducing human intervention leads to
fewer errors and variability in experiments. Despite those
benefits, some labs get more out of this technology than others. Robotic workstations are particularly suited to situations
with invariant workflows. For example, clinical, forensic, and
analytical service labs that run the same tests or assays and
need to automate repetitive tasks. These labs also benefit
from tracking samples and how they were treated, which are
two strong suits of robotic workstations.
Nonetheless, the capabilities of automated workstations keep
growing. As access to this technology expands to more labs,
the applications and modifications will expand as well.
Enhancing the advancement
More than the parts of a workstation matter when it comes
to what it can do. In some cases, advances in one area spawn
improvements in another. The results of those advancing
steps let scientists explore more complex questions, often in more precise ways. For instance, today’s automated
liquid handling technology delivers accuracy and precision
through a wide range of volumes, along with workflow
execution. The ongoing trend of miniaturizing assays to use
less sample requires the ability to work accurately with very
small volumes.
Exploring the economics
Expense comes to mind when any lab manager thinks about
an automated workstation. In the days of gigantic systems,
the cost of robotic liquid handlers far surpassed the budgets
of most labs. Today, some scientists think that automated
systems include an economic incentive, but that’s not necessarily the case.
The financial benefits of robotics are often misunderstood
because there may not be superficial savings. Platforms likely
require the same quantity of consumables and reagents used
in manual methods. However, automation becomes economical over the lifetime of the platform due to reduced retesting,
faster sample accessioning, and improved data integration.
An automated workstation, though, can also save labs money
in other ways. One of the costliest resources in a lab is its
personnel. As sample processing demand can be variable, it is
not cost-effective to immediately hire more staff in response
to increased demand. A robotic system can be a much more
cost-effective solution. The COVID-19 pandemic serves
as an example of this, as labs around the world turned to
automation and robotics to speed up processing and ensure
accuracy in a range of diagnostic tests. These devices can
also reduce or eliminate the risk of repetitive strain injury
that can slow individual or laboratory-wide progress.
“Today’s automated liquid
handling technology delivers
accuracy and precision through a
wide range of volumes, along with
workflow execution.”
27 Lab Manager Automated Liquid Handling Resource Guide
The Benefits of Automated Liquid
Handling for Microscale Samples
Automating sample handling can fill a growing need for applications like DNA
sequencing, protein expression, biological assays, and more
By Kelsey A. Morrison, PhD
To many, the thought of handling microscale samples evokes
an image of tedious manual pipetting. This time-consuming
task can be largely replaced with automated manipulation
of small samples. Automating sample handling can fill a
growing need for applications like DNA sequencing, protein
expression, biological assays, and rapid development of synthetic products.
Despite the initial monetary investment necessary to acquire
these systems, automated sample handling brings distinct
advantages. Laboratories working with small samples by
hand face worker fatigue, reduced precision, and limitations
on experimental throughput. In contrast, investing in automation can bring obvious benefits, from reduced repetitive
strain injuries, greater reproducibility, and increased pro-
28 Lab Manager Automated Liquid Handling Resource Guide
cessing bandwidth. Additional benefits include savings from
fewer wasted samples and reagents, as well as streamlined
workflows. The capability to combine sample preparation
with analytical instrumentation for fully automated synthesis and analysis is another advantage.
Common types of systems for handling
small-scale samples
Likely the most recognizable form of automatic sample
handling, pipette-based systems act as robotic pipetting platforms by dispensing solution from tips through contacting
the deposition target. These pipette-based systems typically
operate through either an air-cushion design for sample
manipulation or with positive displacement via pistons. An
air-cushion system provides more consistent liquid aspiration and dispensing by using a small amount of air between
the liquid and the pipette body to prevent contamination
and ensure greater reliability, especially for small volumes.
For applications requiring higher accuracy and precision of
low-volume samples, positive displacement is preferable over
the lower-cost, lower-precision air-cushion mechanism.
Similar to pipette-based sample handling systems are those
based on syringes and pins, both of which require contact
between the dispensing device and the intended end surface
or solution. All three forms of contact-based liquid manipulation platforms have the potential drawback of cross-contamination.
For laboratories that can afford to invest in an automated
sample handling platform based on mechanisms other than
pipetting, syringes, or pin dispensing, the alternatives may
be better options when high precision and accuracy are paramount, if low- and sub-nanoliter samples are to be processed,
or cross-contamination is a concern. A direct comparison
of results based upon data collected from samples handled
in a tip-based system and in an acoustic droplet ejection
(ADE) platform found statistically different results between
both datasets, with the ADE system appearing to provide
more consistent values. ADE sample handling is also useful
for rapid, microscale synthetic prototyping, which is how it
was applied for automatic reaction scouting of isoquinoline
synthetic building blocks in nanoliter droplets. Microscale
acoustic manipulation has a wide range of potential applications because of its precise control, short dispensing time,
and compatibility with high-capacity sample wells rendering
the mechanism particularly appealing in bioassays.
Other forms of non-contact, high-precision liquid handling
are systems employing microfluidics, solenoid microvalves,
and piezoelectric devices for aliquot ejection as some of the
major classes of liquid manipulation technologies. Beyond
simply a liquid transfer device, automation of sample handling with microfluidics offers the possibility of higher-order
sample preparation, such as sample mixing, separations, and
other preparatory steps for small sample sizes. Automated
liquid handling with solenoid and piezoelectric devices has
demonstrated accuracy and precision that is highly suitable
for sensitive assays, even for picoliter and nanoliter volumes.
“Laboratories working with small
samples by hand face worker fatigue,
reduced precision, and limitations on
experimental throughput.”
Routine calibration
Calibrate regularly to ensure accurate volume
dispensing
Perform diagnostic checks on all moving parts,
including pipette heads and motors
Verify the proper function of air pressure or vacuum
systems
Cleaning
Clean pipette tips between transfers to prevent
carryover (in protocols with sequential steps)
Use disposable tips to reduce the risk of contamination
Monitor and clean the ALH’s components (e.g.,
reservoirs, sample plates) to avoid reagent buildup and
contamination
Environment
Maintain stable temperature and humidity in the lab
Minimize vibrations
If necessary, use pressure stabilization systems to
maintain consistent air pressure
Software
Regularly update software to ensure it runs the latest
protocols and configurations
Review programming sequences to ensure protocols
are set up correctly
Maintenance
Examine tubing for kinks, cracks, or wear that may
disrupt fluid flow
Inspect pipette tips for consistent fitting and replace
any damaged or worn tips
Check for uneven heights on pipette tips
Schedule regular maintenance
Replace air filters, seals, and other consumables as
recommended by the manufacturer
Successfully Maintaining Automated
Liquid Handlers
By Sachin Rawat
Experiments in fields like omics, pharma, and systems biology involve parallel handling of hundreds or thousands of samples. Unlike
manual pipetting, automated liquid handling systems can do this quickly, allowing researchers to spend more time on other tasks. For
optimum function and reliable results, automated liquid handlers (ALHs) require regular maintenance.
30 Lab Manager Automated Liquid Handling Resource Guide Product Spotlight
Freedom from Routine
Pipetting with the ASSIST PLUS
Pipetting Robot
The ASSIST PLUS pipetting robot simplifies liquid handling tasks by automating workflows at an
affordable price. It enables users to achieve superior pipetting accuracy, enhanced reproducibility,
and error-free liquid handling without the need for large-scale automation. Its versatility enhances
the efficiency and precision of a wide range of applications—such as plate filling, reagent addition,
serial dilutions, and magnetic bead-based purifications—making it invaluable for diverse workflows.
Protocols are easy to set up and execute on the ASSIST PLUS using the intuitive user interface or
VIALAB software. Users can navigate menus and adjust volumes with exceptional speed while
minimizing user intervention and reducing the risk of errors. The system is compatible with various
labware and INTEGRA multichannel pipettes, making it ideal for labs seeking a versatile solution to
improve reproducibility and throughput while reducing manual effort.
CLICK HERE TO LEARN MORE
31 Lab Manager Automated Liquid Handling Resource Guide In partnership with
INTEGRA Biosciences is a leading provider of high-quality laboratory tools and consumables for
liquid handling. The company is committed to creating innovative solutions that fulfill the needs of its
customers in research, diagnostics, and quality control within the life sciences markets and medical
sector. INTEGRA’s engineering and production teams in Zizers, Switzerland, and Hudson, NH,
USA, strive to develop and manufacture instruments and consumables of outstanding quality. Today,
INTEGRA’s innovative laboratory products are widely used all around the world, where they help
scientists accelerate scientific discovery. INTEGRA is an ISO 9001 certified company.
www.integra-biosciences.com
