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STRICTLY PRIVATE AND CONFIDENTIAL / Page 1 ACTUATION | FLUIDICS WWW.MEMETIS.COM Shape memory alloy valves for emerging applications in the Life Sciences Microfluidics Symposium: Addressing Challenges in Life Science Fluidics January 19 th , 2021

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Page 1: Shape memory alloy valves for emerging applications in the

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A C T U A T I O N | F L U I D I C S

W W W . M E M E T I S . C O M

Shape memory alloy valves for emerging applications in the Life Sciences

Microfluidics Symposium:Addressing Challenges in Life Science Fluidics

January 19th, 2021

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Life Sciences leave the centralized labs and become broadly available -compact devices for research and analytics increase in functionality

Valves from memetis make even complex analysis devices so compact that they can perform tests directly at the point-of-care - no tedious waiting time for results from a central laboratory

Find out immediately if you are healthy or need treatment

Introduction

Tailor-made medicine and therapy

Valves from memetis enable the safe and automatic operation of cell culture platforms - testing drugs and therapies on-the-chip

Due to their small footprint, the valves are suitable for established 96-well plates andcan help to develop new drugs in 33% less time

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Diagnostics and medical treatment experience substantial change –becoming highly mobile to be used where they are needed

Get medical treatment - when you need it and where you need it

Light and silent

Complex medical treatment devices are heavy and bulky due to a multitude of valves and other components.Microfluidic technology from memetis makes the devices small and portable, so that they can be taken to remote locations and used almost anywhere.

Valves from memetis are so small and energy-savingthat you can even wear them on your body - e.g. in devices for diabetes therapy - without any annoying heat or noise

Introduction

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Introduction

Innovation in many Life Sciences markets driven by Active Fluidic Control

POINT-OF-CARE CELL CULTURE DRUG DELIVERY SYSTEMS

MEDICAL DEVICES LAB-/ ORGAN-ON-CHIP DNA / PEPTIDE RESEARCH

‣ Mobile applications require compact devices with densely packed valves and pumps

‣ Example: On-site virus testing

‣ Successful cell culture development enabled by precise control over growth conditions

‣ Examples: pharmaceutics development, cancer research

‣ Wearing comfort and patient life quality demand lightweight, low-maintenance and silent devices

‣ Long battery life desired‣ Example: insulin dosing

‣ Need for silent operation and highest reliability

‣ Examples: Kidney dialysis control

‣ Additional functionality required to establish realistic conditions

‣ Low heat introduction by valves‣ Example: Blood-brain-barrier

research

‣ Large libraries of liquid constituents need to be dosed and mixed

‣ Low internal volumes save expensive reagents / samples

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Use Case: Pharmaceutics Development

• Pharmaceutical drugs synthesized by living cells• Examples: vaccines, allergenics, gene therapies, tissues, proteins, living medicines for cell

therapy• Challenge: identification and scale-up of cell lines with highest performance

Biological drug development is accelerated by early cell line selection

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Use Case: Pharmaceutics Development

https://www.cytena.com/wp-content/uploads/2020/09/cytena-AppNote_cbird_correlation_09022020V1.pdf

• cytena solution (c.birdTM): create optimum growth conditions already on 96-well-plate level

• Cell cultures based on standardized 24- and 96-well-plates• Patented mixing technology establishes homogeneous growth

conditions within each well, that are otherwise only achievable by large-scale shakers

• Early cell line selection saves months of drug development time

Next-generation of high-throughput Microbioreactor

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Future perspective: active well-by-well fluidic control

96-valve-array will allow individual control over growth conditions in each well

• Limited installation space per valve: 9x9 mm² per well

• Up to 96 valves to be operated at once à low energy consumption required

• Heat dissipation has to be strictly limited to protect cell cultures

• Cross-talk to be omitted• Compatibility with disposable 96-well-

plates required

Vision

• Highly compact, biocompatible miniature valves

• Bistable functionality

Solution

Use Case: Pharmaceutics Development

Challenges

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Active Fluid Control by Shape Memory Actuation

Active fluidic control needs appropriate actuation technology

• Industry standard: Solenoid valves based on electromagnetic actuation

• Miniaturization of solenoids is limited by physical operation principle

• Solution: Shape Memory Alloy (SMA) actuation as a complementing technology

• Electronic control of Solenoid and SMA-driven valves very similar

• First SMA wire-based valve products on the market

10+1

10-0

10-1

10-2

10-3

10-4

10-5

10710-110-210-310-4 106105104103102101100

Mass [g]

Pow

er

densi

ty[W

/g]

Gas turbine

Hydraulicdrive

Petrol engine

Diesel drive

Marine engine

Pneumaticdrive

AC

Piezostack

SMA actuator

Electrorheologic

DC

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Shape memory alloys (SMA) are metallic alloys that can easily be deformed in cold state.As soon as they are heated, for example by electric current, they return to their memory shape

and thereby perform a movement.

Active Fluid Control by Shape Memory Actuation

Actuation by Shape Memory Alloys – the material is the machine

Easy deformation in cold state Heating induces shape recovery

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SMA actuator advantageous in terms of space, weight and shape

• Ultra-low installation space of film actuator

• Low weight due to mostly polymer parts• Low power consumption of thin actuator

Active Fluid Control by Shape Memory Actuation

SHAPE MEMORY ALLOY (SMA)

• Coil actuators always three-dimensional• Miniaturization potential has lower limit

• Mostly metallic parts make valve heavy• Power consumption usually > 1 W

SOLENOID (FOR COMPARISON)

Width: 1.6 mm

Length: 10 mm

Height: 0.02 mm

33% Volume saving*85% weight saving*50% power saving*

* memetis SMA valve compared to solenoid valves (most compact available normally-closed, media-separated valves)

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Dense packaging facilitated by SMA actuators without cross-talk

• No stray-fields impacting with application• Dense packaging without cross-talk

• Polarity-independent (+/- connectors) • Silent due to smooth movement

Active Fluid Control by Shape Memory Actuation

SHAPE MEMORY ALLOY (SMA)

• Magnetic fields reach outside valve housing• Cross-talk may occur when valves close

together• +/- Polarity has to be considered

SOLENOID (FOR COMPARISON)

Pitch: 5 mm

* http://www.hydraforce.com/HFinsider/Dual-Coil_Polarity_Issues/Dual_Coil_Polarity_Issues.htm

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Active Fluid Control by Shape Memory Actuation

• memetis shape memory technology allows for innovative and adaptable solutions

• Unique expertise in foil actuation only commercially available from memetis

MEMETIS EXPERTISE: PLANAR ACTUATION USING SMA FOILS

memetis actuators made from thin foils enable unique specifications

Variable mechanical integration ✓Extreme design freedom for customization ✓Customer specific actuator geometry (2D) ✓Large range of force and stroke ✓Smallest installation space ✓Highest work density ✓Easy electrical integration (low voltages) ✓Silent operation ✓Robust & reliable design ✓

A

B

UN

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E F

EA

TU

RES O

F

SM

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OIL

ACTU

ATIO

N

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Unique SMA actuators from memetis enable valves specifically designed for life sciences and challenging miniaturized tasks

Valving technology by memetis

NC-valve “Series 09“ Bi-stable valve

• Media-separated allrounder for microfluidics

• Usable as proportional valve (closed loop)

• Liquids and gases• Tight stacking by pitch of 5 mm• Low power consumption <0.2 W

• Ultra-power-saving valve• Media separated, similar to

NC/NO-Valve• Fast and power saving: Current

only for switching (<40 ms @ 1A)• Compatibility to 9x9 mm 96-

wellplate format is planned

Let us know about your

needs and participate in our poll!

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Valving technology by memetis

ACTUATION PRINCIPLE

LARGE FORCES IN SMALL

DIMENSIONS

FOIL ACTUATOR

INTEGRATED FLUIDIC SYSTEMVALVES

A

B

NO/ NC VALVE BISTABLE VALVE 3/4-WAY NC VALVE

• Pressure up to 2 bar• Life span >1,000,000 cycles• Ultracompact design• No switching noise (<20 dB)• Low internal volume (< 4 µl)

• Pressure up to 2 bar• Life span >1,000,000 cycles• Ultracompact design• No switching noise (<20 dB)• Low internal volume (< 4 µl)

• Pressure up to 2 bar• Life span >1,000,000 cycles• Ultracompact design• No switching noise (<20 dB)• Low internal volume (< 4 µl)

memetis offers wide range of solutions and

products

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Strong foundation for future growth – memetis in 60 seconds

Company overview

COMPANY RESEARCH CLIENTS

PERSONNEL CAPABILITIES AWARDS

‣ Founded 2017‣ One-Stop Shop from ideation to

series production‣ Own research and

manufacturing facilities

‣ > 20 years of research‣ > 50 topic-related scientific

publications‣ 6 patents / patent applications

‣ 55 % valve related clients‣ 32 % international clients‣ + 50.000 p.a. produced for

one client

‣ 13 employees‣ 3 PhD, 7 Master degrees,

3 Bachelor degrees‣ Interdisciplinary backgrounds

‣ Rapid prototyping via 3D, milling, laser cutting etc.

‣ Series production for up to 100.000 pieces p.a.

‣ 1st place Elevator Pitch BW‣ Cyber Champions Innovation‣ Finalist WECONOMY‣ 2nd Cyber One Award‣ 1st KIT Venture

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Have we sparked your interest? – Contact us!

Dr. Hinnerk Oßmerp: +49 721 47000240

e: [email protected]

Christoph Wessendorfe: [email protected]

EAGER TO MEET YOUR CHALLENGE

www.memetis.com

You want to stay up to

date on memetis’ products

and developments? FOLLOW US ON LINKEDIN!

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SPECIFICATIONS

NC valve “Series 09” – the media-separated allrounder

Appendix

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SPECIFICATIONS

Bistable valve – the ultra power-saving option

Appendix

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SPECIFICATIONS

Vent valve for gas control – high flow rate at low pressure

Appendix

• Developed for security application• In-wall mounting• Ideal for combination with piezo pump

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Appendix

Electronic control units and evaluation kits

• 5V USB-powered• Pre-programmed and adjustable current supply

profiles• Manual control via push button• Automated control via digital IO channels or I2C

interface

ü Two-channel version

included in evaluation kits

ü Suitable for monostable

and bistable valve variants

ü Eight-channel version will

become available in 2021

üAdd-on module will allow

control of up to 96 bistable valves

SPECIFICATIONS

Get startetnow!

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Appendix

Application-specific platform solutions

• Target applications: Research & development, academics, Start-ups, laboratory equipment

• Quick-start solution, e.g. for cell cultivation, process development, organ-on-chip

• Tailor-made and configurable systems for complex fluid control

• Selection of exchangeable fluid control and sensing modules

• Extendable plug&play solution

• Integration interface for custom fluidic chipsChip integration

Fluidic connectionMiniature valve Pump

Biocompatiblematerials

OFFER

Contact us for an

individual solution!

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SPECIFICATIONS

Various stand-alone actuation solutions

UA0203 UPSTROKE-ACTUATOR

Appendix

Examples: pinch valves,

disposable chip valves,

optics and sensor adjustment

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SPECIFICATIONS

Various stand-alone actuation solutions

TA0301 TILT-ACTUATOR

Appendix

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SPECIFICATIONS

Various stand-alone actuation solutions

IP0301 IN-PLANE-ACTUATOR

Appendix

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‣ Proportional control only closed loop investigated up to now

‣ Quality control 100% functionality test of flow rate and switching times @1 bar, RT

‣ Tests under harsh conditions for major design changes: T = 55 °C, storage conditions, vibration/impact

‣ Continuous control allows for exact regulation of flow rate even at flow-rates well below nominal value.

‣ Open-loop control to be tested regarding repeatability.

Proportional control characteristics

PROPORTIONAL CHARACTERISTICS

* increases power consumption

stand-alone valve. All three connections were tested up to a

pressure difference of 400 kPa and showed no leakage.

5 Characterization of the SMA multi-portmicrovalve

The characterization of the fluidic properties of the SMA

multi-port microvalve was first carried out in a tensiletesting machine. By this it is possible to measure simul-

taneously the force–displacement behavior required for

closing as well as the pressure-dependent flow rate. InFig. 12 the closing force and the pressure dependent flow

rate are shown as a function of the crosshead moving.

For a better understanding the individual steps aredescribed below: (I) A pressure difference is applied to the

inlet and the spindle of the tensile machine is moved

towards the valve seat until a force is detected. (I ? II)The force increases due to the elastic behavior of the

membrane and the applied pressure difference. At this state

the flow rate remains still at the pressure-depending valuedue to a sufficiently large flow-through area. (II ? III) As

the valve seat approaches, the force decreases rapidly, and

the flow rate drops to zero.These curves can be used to determine (1) the force

required by the actuator, (2) the force–displacement

behavior of the compression spring and (3) the expectedpressure-dependent flow rate. A force of 75 mN is required

to close or seal the valve for an applied pressure differenceof 50 kPa. If the pressure is increased, this necessary

closing force increases by about 1 mN per 1 kPa. Also the

flow increases from a value of about 1000 ml/min by about10 ml/min per 1 kPa.

5.1 Open loop control

The multi-port valves are suitable both for liquid media as

well as for gases. Figure 13 shows the flow of an NC SMAmulti-port microvalve as a function of the electrical heating

current at different pressure differences. To open the valve,

a minimum heating current of more than 100 mA is re-quired, which decreases for higher applied pressure dif-

ferences. For a heating current of 300 mA the valve is

completely open.The same measurement was also carried out with liquid

medium (water) and is shown in Fig. 14. The heating

currents for opening ([ 130 mA) as well as reaching acomplete open state ([ 400 mA) are higher compared to

Fig. 10 Photograph of an assembled SMA multi-port microvalvehaving outer dimensions of 12 9 11 9 9 mm3 (without tubingconnectors)

Fig. 11 Variants of fluidic connections for the SMA multi-portmicrovalve. a Flange connectors, b push-in fitting and c tubingconnectors

Fig. 12 Force (idle line) and flow (dotted line) depending on thedistance between a valve plunger and the valve seat for variouspressure differences

Fig. 13 Open loop control at one port of a SMA multi-portmicrovalve with nitrogen gas as test medium

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the gaseous media. The reasons for this are (1) the higher

viscosity of water and the associated higher closing forceas well as (2) an increased heat transfer.

5.2 Closed loop control

In addition to the static investigation of the valve behavior,

dynamic investigations were also carried out. In this case,three flow sensors with different properties were connected

between the pressure source and the inlet of the valve. Thedifferent sensors are necessary to measure the response

times as well as a precise flow rate with the same setup.

The control of the valve is realized by by a microcontroller(Arduino). Figure 15 shows the complete setup for flow

regulation consisting of the valve, the three flow sensors

(FS 1, FS 2 and FS 3) and the fluidic periphery.

5.3 Control results

Figure 16 shows the time-dependent closed loop-controlled

flow rate for 900 ml/min (@100 kPa) of the three flow

sensors and the required heating current. In this case a PIDcontrol was used. In particular, the proportional (P) and

integral (I) elements were heavily weighted, as the aim was

not to achieve particularly fast control, but to achieve apreferably exact control. The average heating current in

this case is about 200 mA.

5.4 Multi-port behavior

Table 1 shows the resulting flow rates for nominal flows of300 and 600 ml/min (nitrogen) in the inlet ports for an

applied pressure difference of 100 and 200 kPa and the

resulting flow in the common outlet port. The flow rate ofthe inlet and outlet ports are averaged over a time period of

30 s. The results show a control accuracy of 1 ml/min

deviation from the setpoint in the inlet ports. The higherdeviation of the common outlet is due to the read out of the

sensor signal. The blue color shows the measurements by

the MKS and the green color by the AWM flow sensor.Figure 17 shows the results of the same measurement

for a longer period (30 s), a setpoint value of 900 ml/min

and an applied pressure difference of 100 kPa.

Fig. 14 Open loop control at one port of a SMA multi-portmicrovalve with water (DI) as test medium

Fig. 15 Complete setup for flow regulation consisting of the valve,the three flow sensors (FS 1, FS 2 and FS 3) and the fluidic periphery

Fig. 16 Time-dependent flow rate (@100 kPa) of the three flowsensors and the required heating current

Table 1 Mixing behavior of nitrogen gas for different pressurizedinlet ports in a common outlet

Inlet 1 (ml/min) Inlet 2 (ml/min) Outlet (ml/min)

100 kPa 300.78 299.68 604.41

300.01 599.50 897.03

599.83 299.19 897.69

200 kPa 300.20 299.53 603.36

300.40 600.53 898.45

600.66 299.90 897.44

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the gaseous media. The reasons for this are (1) the higher

viscosity of water and the associated higher closing forceas well as (2) an increased heat transfer.

5.2 Closed loop control

In addition to the static investigation of the valve behavior,

dynamic investigations were also carried out. In this case,three flow sensors with different properties were connected

between the pressure source and the inlet of the valve. Thedifferent sensors are necessary to measure the response

times as well as a precise flow rate with the same setup.

The control of the valve is realized by by a microcontroller(Arduino). Figure 15 shows the complete setup for flow

regulation consisting of the valve, the three flow sensors

(FS 1, FS 2 and FS 3) and the fluidic periphery.

5.3 Control results

Figure 16 shows the time-dependent closed loop-controlled

flow rate for 900 ml/min (@100 kPa) of the three flow

sensors and the required heating current. In this case a PIDcontrol was used. In particular, the proportional (P) and

integral (I) elements were heavily weighted, as the aim was

not to achieve particularly fast control, but to achieve apreferably exact control. The average heating current in

this case is about 200 mA.

5.4 Multi-port behavior

Table 1 shows the resulting flow rates for nominal flows of300 and 600 ml/min (nitrogen) in the inlet ports for an

applied pressure difference of 100 and 200 kPa and the

resulting flow in the common outlet port. The flow rate ofthe inlet and outlet ports are averaged over a time period of

30 s. The results show a control accuracy of 1 ml/min

deviation from the setpoint in the inlet ports. The higherdeviation of the common outlet is due to the read out of the

sensor signal. The blue color shows the measurements by

the MKS and the green color by the AWM flow sensor.Figure 17 shows the results of the same measurement

for a longer period (30 s), a setpoint value of 900 ml/min

and an applied pressure difference of 100 kPa.

Fig. 14 Open loop control at one port of a SMA multi-portmicrovalve with water (DI) as test medium

Fig. 15 Complete setup for flow regulation consisting of the valve,the three flow sensors (FS 1, FS 2 and FS 3) and the fluidic periphery

Fig. 16 Time-dependent flow rate (@100 kPa) of the three flowsensors and the required heating current

Table 1 Mixing behavior of nitrogen gas for different pressurizedinlet ports in a common outlet

Inlet 1 (ml/min) Inlet 2 (ml/min) Outlet (ml/min)

100 kPa 300.78 299.68 604.41

300.01 599.50 897.03

599.83 299.19 897.69

200 kPa 300.20 299.53 603.36

300.40 600.53 898.45

600.66 299.90 897.44

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6 Conclusions and outlook

In this publication the integration of two individual SMA

foil actuators to a multi-port microvalve was shown for thefirst time. A 3/4-way valve was realized with mechanically

and electrically independent actuators that are fluidically

connected. The valve performance was investigated foroperation in an open as well as a closed loop control. The

presented valve layout in principle allows for extremely

compact integration of more than two valves in a commonhousing to increase the fluidic complexity. The membrane

(PDMS) and the fluidic part (PEEK) are made of bio-

compatible materials, whereby the valve can be used forin vitro biological investigations. In particular, the precise

mixing or separating of media is important for these pro-

cesses, as demonstrated in this publication. For the givenvalve concept different fluidic connections are presented

enabling to operate the valve as stand-alone device or to

flange it to fluidic periphery.Further improvements should be made to the flow con-

ditions to reduce the dead volume in the chamber and

pressure peaks in the outlet. Also it would be interesting tointerconnect to increase the fluidic complexity.

Acknowledgements This work was performed at the Institute ofMicrostructure Technology (IMT) at the Karlsruhe Institute ofTechnology (KIT) and the memetis GmbH. The authors thank M.Sc.Florian Bruderlin and Dr. Dario Mager for providing lab equipmentand helpful support.

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Fig. 17 Time-dependent flow rate (30 s, @100 kPa) s and heatingcurrent

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Appendix