© 2016 Artel

Introducing New Technology for

Liquid Handling Quality Assurance Bill Gigante and John Bradshaw Ph.D.

© 2016 Artel

Tutorial Topics

Product overview

Technical Need – Compound Management

Technology

Operation

Maintenance

Applications

General topics

Typical questions

Your questions

© 2016 Artel

PRODUCT OVERVIEW

© 2016 Artel

Product Overview

Using a novel pressure based technology, the Artel VMS™ measures

volumes of liquids or solids in 96- and 384-well plates

Technology developed with Compound Management and Screening

in mind

Measurement is independent of shape of well, type of plastic, and

color of material

Can measure volumes between 5-500 µL

CV < 2% (plate dependent)

Accuracy <5 µL (plate dependent)

Automation friendly

© 2016 Artel

Has anyone experienced any of these issues?

Empty wells

Low volumes in wells

Clogged pipette tips

Bad tip or plate lots

Database discrepancies

Liquid loss from plate seal

Liquid loss from tip carryover

Poor liquid class definitions

Mechanical failures over time

These are issues that can be resolved with real-time volume

detection. i

© 2016 Artel

Technical Need Compound Management

© 2016 Artel

Technical Need

Most big pharma and biotech companies have a Compound Management group

Compound Management groups store and maintain…

Chemical libraries

Biologics

Reagents

Compound Management groups support…

Drug screening

Clinic trials

Chemistry

Compound Management

© 2016 Artel

Typical Workflow

External

Samples

In-house

Samples Storage

Request

Placed

Samples

put in

plates

Distributed

to

Requestor

Screened

Replenish

Samples

Hits are re-ordered (i.e. IC50 Plates)

= Where Artel VMS can be used

© 2016 Artel

Artel VMS Saves Money

Real time sensing of volume discrepancies

Early detection of liquid handler malfunctions

Early detection of clogged tips

Detection of database errors

Corrects for errant data in LIMS

Enables fine tuning of pipetting steps for sensitive assays

Enables pre- and post- checking of volume additions

Enables process verification

© 2016 Artel

Technology

© 2016 Artel

Measuring Volume with Pressure

Ideal gas law: PV=nRT

If you know the pressure and the temperature, you can solve for a

volume.

The Artel VMS adds a known volume of air to each well.

A strain gauge pressure sensor provides feedback which can be

calibrated to a volume.

An internal set of wells are used to normalize temperature and

barometric changes.

Not subject to issues normally seen by optical or acoustic methods of

measurement.

© 2016 Artel

Measurement Details

• A bank of 8 syringes

pressurize a column of

wells on a plate

• The pressure is measured

with a sensor

• The measurement is

compared to the stored

calibration curve for the

specific plate

• A result is generated

© 2016 Artel

Pressure Curve of individual sensors at 80 Hz

© 2016 Artel

Sensor Data converted to Volumes

© 2016 Artel

Artel VMS Operation

© 2016 Artel

Artel VMS Operation

Calibrate Plate

Type

Select plate and

wells to

measure

Results are also

saved as a .csv

file in a

preselected

folder

30 (96 well) or

120 (384 well)

seconds later,

results appear

on screen

Press “Run

Plate” and enter

or scan plate

name

Occasionally run

maintenance

program

© 2016 Artel

Plate Calibration

Most 96 and 384 well SBS plates <20mm high can be calibrated on

the VMS

A pressure-to-volume curve can be generated by measuring full wells

and empty wells

High precision metal

cylinders are used

during the calibration

procedure

Operator enters basic

plate information

© 2016 Artel

Plate Calibration Procedure

Volume of metal cylinders are entered into appropriate columns

© 2016 Artel

Metal Cylinders used as Volume Standards

Appropriate metal cylinder is added to the plate

242 µL 67 µL 43 µL

© 2016 Artel

Calibration Curves

After plate is run, calibration data is presented on the screen

© 2016 Artel

Running a plate

• Select from dropdown list of

calibrated plates

• If needed, add a shim

• Enter or scan plate name

• Press “OK”

© 2016 Artel

Results are displayed

© 2016 Artel

Maintenance

© 2016 Artel

Maintenance

Cleaning pad is provided for

occasional cleaning

Seal bar can be removed for

thorough cleaning

© 2016 Artel

Applications

Accurate Normalization of Grain Samples

Measuring Volume Changes in Screening Plates

© 2016 Artel

Application #1: Accurate Normalization of Grain Samples

Volumes of solids can be determined by VMS

Volume data can be used to calculate the volume of reagent

needed to perform quantitative extractions

© 2016 Artel

4 varieties of seeds were added to

the wells of a plate (popcorn, rice,

lentils, and barley)

VMS was used to determine volume

of seeds in each well

Total volume of 200uL/well was

desired

Blue water added to each well to

simulate normalization

200uL – Seed Volume = Amount

of water added

Plate was reread on the VMS

Experiment

Application #1: Accurate Normalization of Grain Samples

© 2016 Artel

Chart 1 – Volume of

seeds determined

by VMS

Chart 2 – Volume of

well after water was

added to the seeds

Results

Application #1: Accurate Normalization of Grain Samples

© 2016 Artel

Application #2: Measuring Volume Changes in Screening Plates

Screening plates can be left

exposed waiting for testing for

several hours

Environmental conditions (humidity,

temperature, pressure) can affect

sample integrity or experimental

results

Some fluids evaporate and others

absorb moisture from the air

Small changes in sample volume

due to environmental conditions can

be hard to track

© 2016 Artel

Half of a 384 well plate was

filled with DMSO

The other half was filled with

Water

2 plates were made; one was

covered, one was not

Every hour the volume of

each well of each plate was

measured on the VMS

(covered and non-covered)

8 hours total

Experiment

Application #2: Measuring Volume Changes in Screening Plates

© 2016 Artel

DMSO side absorbed water, gained up to 8uL per well

Water side evaporated, lost up to 8uL per well

Covers help!

Results

Application #2: Measuring Volume Changes in Screening Plates

© 2016 Artel

Interface between water and DMSO showed the most dramatic change

Some edge effects were seen

Results – Heat Map of Uncovered Plate Application #2: Measuring Volume Changes in Screening Plates

Percentage Change from initial starting volume of 50uL 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24

A 18 17 16 16 15 16 15 15 15 16 17 18 -20 -17 -16 -16 -15 -15 -15 -15 -15 -15 -16 -17

B 17 16 15 15 15 15 15 15 15 16 16 19 -20 -17 -16 -15 -15 -14 -14 -14 -14 -14 -15 -16

C 17 15 15 15 15 15 15 15 15 16 16 18 -19 -16 -15 -14 -14 -14 -14 -14 -14 -14 -15 -15

D 16 15 15 15 15 15 15 15 15 16 16 19 -20 -17 -15 -15 -14 -14 -14 -14 -14 -14 -15 -15

E 16 15 15 15 15 15 15 15 15 15 16 18 -19 -16 -15 -14 -13 -13 -13 -13 -13 -13 -13 -15

F 16 15 15 15 15 15 15 15 15 16 16 18 -20 -16 -15 -14 -14 -13 -13 -13 -13 -13 -14 -15

G 16 15 15 15 15 14 15 15 15 16 16 18 -19 -16 -15 -14 -13 -13 -13 -13 -13 -13 -13 -14

H 16 15 15 15 15 15 15 15 15 15 16 18 -20 -16 -15 -14 -14 -13 -13 -13 -13 -13 -14 -15

I 17 16 16 16 16 15 15 16 16 16 17 19 -20 -16 -15 -14 -13 -13 -13 -13 -13 -13 -13 -14

J 17 16 15 15 16 15 16 16 16 16 17 19 -19 -16 -15 -14 -13 -13 -13 -13 -13 -13 -13 -14

K 17 16 16 16 16 16 16 16 16 16 17 19 -20 -16 -15 -14 -13 -13 -13 -13 -13 -13 -13 -14

L 17 16 16 16 16 15 16 16 16 16 17 18 -19 -16 -15 -14 -13 -13 -13 -13 -13 -13 -13 -14

M 17 17 16 16 16 16 16 16 16 16 17 19 -19 -16 -15 -14 -14 -13 -13 -13 -13 -13 -14 -14

N 17 16 16 16 16 15 16 16 16 16 16 18 -19 -16 -15 -14 -14 -14 -13 -13 -14 -14 -14 -15

O 17 17 17 16 16 16 16 16 16 16 17 18 -20 -17 -16 -15 -14 -14 -14 -14 -14 -14 -15 -15

P 19 18 17 17 17 17 17 17 17 17 17 18 -20 -17 -16 -16 -15 -15 -15 -15 -15 -15 -15 -16

© 2016 Artel

General Topics

© 2016 Artel

Automation Friendly

Plate tray was designed with robotics in mind

Fully documented API available

2 integration demo applications with source code

are provided

© 2016 Artel

Typical Customer Use Cases

Real time process verification

Process optimization

Automated pipette verification

Liquid class optimization

Liquid class optimization during design of novel instrumentation

QC of reagent addition during PCR

QC of incoming collections of materials

Where does volume matter in your lab?

© 2016 Artel

Places Where Volume = Quality

Pharma/Biotech

R & D

Pharma/Biotech

QC Groups

Contract Labs

Forensic Labs

Public Health

Labs

Pharma/Biotech

Preclinical/

Clinical

Development

Groups Pharma/Biotech

Compound

Management

& HTS

Automated

Pipette

Manufacturers

© 2016 Artel

Typical Questions

© 2016 Artel

Questions Before the Q&A

How do you deal with cross-contamination?

Can the Artel VMS be integrated?

What is the tallest/shortest plate it can read?

Can the Artel VMS read tube racks?

Can the Artel VMS read barcodes?

How fast can it read a plate (96/384)?

What do the results look like and are they configurable?

What if the liquid has bubbles?

What if the liquid is stuck to the side of the well?

What CV and accuracy should I expect?

© 2016 Artel

Questions?