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Standards for connecting microfluidic devices?
Henne van Heeren*
DOI: 10.1039/c2lc20937c
The field of microfluidics is maturing
slowly but steadily and new products are
entering the market, showing a bewildering
number of technologies and formats. This
article states the need for standards for
microfluidic interconnections, chip
dimensions and a vocabulary. It also
explains where and why those standards
might be useful. A description of the
ongoing standardization activities is given
and the need for further work is explained.
Why standards?
Although we are seldom aware of them,
standards are found everywhere. Without
even thinking about it, we install a new
device with a USB connector and we
screw in a new light bulb (although
perhaps the last one available) in a fitting.
However, we do not miss standards much
where they do not exist: we buy without
protest the umpteenth slightly different
charger for our newest mobile gadget.
But industrialists know that, in general,
standards promote the uptake of new
technologies. Firstly, standardized prod-
ucts and services are perceived by users as
safer, more secure, and having higher
quality. But also designers know them to
fit better into existing infrastructure and
sales managers accept them to enable
multi-market access and to create more
active markets. In short: standardization
is expected to lay a solid foundation upon
which new products will be developed.
But are there also specific benefits from
a microfluidic perspective? In fact there
are several. Researchers do not want to
spend much time on side issues like
correct connection of tooling; they also
want to use chips from different suppliers
without needing to change their whole
experimental setup; and they want their
developed products to go as smoothly as
possible into production. Providers of
analytical services do not want their
limited lab space cluttered with a multi-
tude of incompatible instruments.
Chemical engineers want easy intercon-
nection between pumps, sensors and
reactors. And, finally, operational
managers want a second source for their
products.
Developing standards must be
a bottom-up process to generate broad
support and to ensure it addresses the
right issues and offers the most appro-
priate solutions. The whole community,
from researchers to end users, should give
input, firstly to ensure as much room as
possible for further developments, second
to ensure fitness for use.
A group of microfluidic industrialists
started a consortium
1
in 2009 to discuss
and promote the uptake of microfluidic
technologies and products. In this
consortium the whole microfluidic supply
chain is represented, from supplier to
user, from SME to large enterprise. With
an awareness of the importance of stan-
dards in mind, the consortium took up the
challenge to discuss them with its
members. Right at the beginning of the
discussion it became clear that micro-
fluidic interconnections were to become
the major point of discussion. Such
interconnections should enable users to
make a number of fluidic connections
easily, as well as be fast and reliable. No
intensive training should be needed, so no
need to change the existing infrastructure
or acquire expensive devices. Only modi-
fication of the design rules is needed.
Barriers
Although standards have been beneficial
in specific cases, it does not mean the
introduction in new areas will go
smoothly. A very important barrier to
implementation relates to the market
position of the companies. Companies
that have a market dominance or are ex-
pecting to achieve such dominance are
less likely to support standard initiatives.
This relates also to the fact that invest-
ment in current products might become
worthless as a consequence of an accepted
standard. Another barrier, and especially
valid for microfluidics, is the diversity in
the existing products already on the
market. This diversity is partly based on
the wide range of microfluidic applica-
tions. An interconnector for disposables
to be used in Point of Care devices (low
pressure, room temperature, water based
liquids) will clearly be different from an
interconnector for analytical instruments
working with gases at high pressure. One
must therefore accept in these discussions
that not all organizations will support
standardisation, and there will be
different standards for different applica-
tions. Discussions will be complex, and
further complicated by the lack of
uniformity in our vocabulary: we use
words like: carrier, tray or support;
interface, adapter, coupler, bus, manifold
or connector; chip-holder, package or
cartridge. Words that are overlapping in
their meaning and not always consistently
used.
Also researchers as a rule tend to prefer
design freedom and flexibility above the
easier route to commercialization that
standards offer. That this also prohibits
the use of qualified, reliable microfluidic
components is a disadvantage seldom
enablingMNT, Drakensteynlaan 34, 3319 RG,
Dordrecht, The Netherlands. E-mail: henne@
enablingMNT.com; Tel: +31 786300748
1022 | Lab Chip, 2012, 12, 1022–1025 This journal is ªThe Royal Society of Chemistry 2012
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realized. Every minute spent on creating
a breadboard test setup from non-fitting
components is a minute less spent on
experiments.
Furthermore, as many companies are
already making microfluidic products and
those products are currently being used in
established industries, one must also take
into account the existing infrastructure
and the standards used in those older
industries.
2
A few of these will be dis-
cussed in the next section.
Existing standards and standards
in development
Microscope slide
The pro forma standard of the microscope
slide has been around as nearly as long as
there are microscopes themselves. An-
thonie van Leeuwenhoek, the inventor of
the microscope, or at least the first person
reported to have used such an instrument
for scientific purposes, used a microscope
slide of approximately 1 by 3 inches. Due
to its long history it was not possible to get
an agreement on the exact size, so the
official document describing the stan-
dard
3
states that the dimension should be
between 75–76 mm and 25–26 mm,
respectively. This helps explain the large
diversity of products in the market.
Microscope plates have also become
popular as a carrier for microfluidic
structures. Microfluidic products based
on the microscope slide format are either
created by structuring a polymeric layer
on top of the glass plate or by micro-
moulding a polymeric structure to it. The
first technology is typically used by
academic researchers, the second by
professional companies. The micro-
moulding technology has several impor-
tant advantages, one of them is the option
of creating ports which can be used with
mini-luer interconnects. There is no
general agreement about the layout of the
microfluidic (or electrical) ports, although
a pitch of 4.5 mm (similar to the micro-
titerplate pitch) and a positioning on the
long side of the slide seem more or less
accepted as standard (see Fig. 1).
Microtiterplate
Common usage of the microtiterplates
began in the late 1950s. A series of stan-
dards was proposed in 2003 and pub-
lished by the American National
Standards Institute (ANSI) on behalf of
the Society for Biomolecular Sciences
(SBS). There are now several generations:
plates with respectively 96, 384 and 1536
wells. Although there are no physical
limitations to make even smaller wells, its
practical use is limited by the fact that
accurate pipetting of small volumes
becomes increasingly difficult and also
evaporation and trapped air bubbles
hinder efficient use.
4
The microtiterplate-
based microfluidic devices are in general
produced using polymer as a construction
material, the interconnects are enabled by
integration of ferrules and can be used for
instance with Luer connectors. Micro-
fluidic devices based on this standard use
one or more well positions for micro-
fluidic contacts, mostly those at the outer
rim of the chip, with pitches of 4.5 mm or
9 mm. The titerplates have outer dimen-
sions of 127.76 85.47 mm
2
.
45 15 mm also a standard?
Although the standard formats
discussed above have the advantage to fit
with the existing users’ infrastructure,
they have a disadvantage of being ineffi-
cient for suppliers working with glass
wafers. Those suppliers prefer, for cost
reasons, chips to be as small as possible
and they like the chip sizes to be
compatible with the standard wafer
dimensions. There is no general agree-
ment about those chip sizes, but
chip dimensions of 45 15 mm are rather
popular with companies producing and
using glass chips. Interconnections are
enabled by clamping a connector with a
flat interface or using a reusable chi-
p holder to facilitate handling and
ensuring connection to the outer world
(see Fig. 2).
Other (proto) standards of
interest
SEMI MS7-0708----specification for
microfluidic interfaces to electronic
device packages
5
This document defines an industry-stan-
dard for fluidic interfaces with electronic
devices. The specification describes the
connection attributes and specifies the
interface dimensions required to design
and build devices and systems that are
compliant with this standard. The goal is
to enable devices from different vendors
to interconnect via an open architecture.
The specification is intended as an
enhanced capability to state-of-the-art
electronic device technologies incorpo-
rating a combination of electronics and
fluidics. It is also intended to provide
device users adequate room for product
versatility and market differentiation
without the burden of carrying obsolete
interfaces, losing compatibility, and
choice.
SEMI MS6-0308----guide for design and
materials for interfacing microfluidic
systems
6
This document provides guidelines for
general fluidic interface design and mate-
rials selection that can reduce redundant
engineering effort and lead to improved
design, manufacturability, and operation.
Fig. 1 Examples of microfluidics using the microscope slide format (Courtesy: Microfluidic
ChipShop).
This journal is ªThe Royal Society of Chemistry 2012 Lab Chip, 2012, 12, 1022–1025 | 1023
SEMI MS9-0611----specification for high
density permanent connections
between microfluidic devices
7
This standard provides specification for
interconnection dimensions and perfor-
mance requirements for permanent mi-
crofluidic interfaces. It also provides
guidance for interface design. This will
help to enable low cost and high volume
manufacturing of products having high
density permanent interfaces between
plastic tube adapters, plastic microfluidic
cartridges, and electrofluidic devices.
ISO 10991:2009 microprocess
engineering----vocabulary
8
This document gives terms and definitions
for microprocess engineering applied in
chemistry, pharmacy, biotechnology and
food technology.
SEMI Draft Document 4691,
specification for high density
permanent connections between
microfluidic devices (not yet approved)
This proposal for multiport interconnects
is in discussion. It describes an inter-
connector with 8 parallel fluidic
tubes with a center to center spacing of
0.500 mm and an ID of 0.250 mm.
Other
Nessi (New Sampling/Sensor Initiative)
discusses sampling devices for the process
control instrument.
9
The DIN standardization group on
microreaction technology, which created
ISO 10991:2009 (see above), is now
working on standard characterization
processes for microreactors.
At the beginning of this century mi-
crofluidic breadboards and backbones
were proposed to be able to interconnect
different microfluidic components from
different suppliers. There was, however,
no sufficient industrial momentum to
pursue this goal at that time.
It must be said that the uptake of these
standards, perhaps maybe for the Nessi
standard, seems to be limited.
Is this enough?
At first sight there seems to be enough
going on in microfluidic standards, so
why is more standardization needed?
From discussion with several companies
active in microfluidics and (potential)
users, we concluded that there is a benefit
if users can use chips from different
suppliers in their instruments. This
enables testing for the best chip on the
market, secondary sourcing, and, far
more ambitious, the potential of doing
several different tests with one single
instrument. This last factor will increase
in importance with the increasing use of
microfluidic based instruments in labo-
ratories and even more, when they are
introduced in places where a diversity of
microfluidic tests are to be used by
unskilled workers in a lab space of limited
size. This provides a need for compact,
multifunctional, easy to use instruments.
For such ‘‘plug and play’’ instruments,
standardized interconnects are an essen-
tial requisite. Similar to electronic inter-
connects, this will not be one universal
connector, but a couple of standardized
ones, each for a specific technology
application space. This will mean a limi-
tation to the number of instruments that
companies can sell. This is less of
a problem for those companies than one
would think, the main aspect of the busi-
ness in microfluidic testing for Point of
Care is in the consumables, not so much
the instruments!
For these reasons the Microfluidics
Consortium set up a program to work
towards this goal, realizing this was
a ‘‘man on the moon’’ project with many
risks, but also seeing many advantages to
be gained on the way forward. One thing
must be accepted: the initiative must be
broadly carried, suppliers as well as users
of those products should be involved. The
program should involve agreements
about: vocabulary, chip dimensions, port
layout, standard multiport inter-
connectors and, perhaps at a later time,
sample volumes.
Fig. 2 Example of a chip holder with a 45 15 mm chip (Courtesy: Micronit Microfluidics).
Fig. 3 Dolomite Microfluidics, 2011, example of MultifluxConnectors and Multiflux
Compatible Interfaces.
1024 | Lab Chip, 2012, 12, 1022–1025 This journal is ªThe Royal Society of Chemistry 2012
Our group has now started to work on
the following program:
(1) Describe and formalize port layouts
for flared/flanged interconnects, i.e.,
clamped interconnects for bare chips as
for instance those shown in Fig. 3. These
kinds of connectors are suitable for all
types of devices regardless of which
material they are made. They also work at
higher temperature and pressure regimes
and show smaller dead volumes
compared to, for instance, ferrule based
connectors.
(2) Describe and formalize the often
used port layouts on the microtiterplate
and microscope slide chip formats.
(3) Describe and formalize port
layouts for 45 15 mm chips in
chip holders. Chip holders are the best
choice for experiments using different
chips. This discussion may lead to
standardized interfaces for analytical
instruments.
(4) Discuss the need for standards for
spinning microfluidic devices (based on the
CD standards) and the credit card format.
(5) Write a taxonomy of terms used in
relation to microfluidic packaging and
interconnections (in discussion with
SEMI and ISO which have both already
started to work on this).
(6) Devise an interconnect system for
low cost reusable chips.
In conclusion, we can say that ulti-
mately there will be a situation where only
a limited number of instruments will
handle a wide range of disposables and it
will be easy to connect components
and systems from different suppliers.
How to get there is as yet unknown, but
standards will come and will play an
essential part.
References
1 The Microfluidic Consortium,
www.cfbi.com/index_files/microfluidics.htm.
2 H. Becker, One size fits all?, Lab Chip, 2010,
10, 1894–1897.
3 ISO 8037–1:1986, Optics and Optical
Instruments----Microscopes----Slides----Part 1:
Dimensions, Optical Properties and
Marking.
4 P. Telleman, Microfluidics----Satisfying the
Needs of Research and Industry, Business
Briefing Pharmatech, 2003.
5 This standard was technically approved by
the global MEMS Committee,
www.semi.org.
6 This standard was technically approved by
the global MEMS Committee,
www.semi.org.
7 This standard was technically approved by
the global MEMS/NEMS Committee,
www.semi.org.
8 ISO 10991 was prepared by Technical
Committee ISO/TC 48, Laboratory
equipment, www.iso.org.
9 ISA-SP76, Composition Analyzers.
This journal is ªThe Royal Society of Chemistry 2012 Lab Chip, 2012, 12, 1022–1025 | 1025
