Robotics to Control Droplet Movement Remotely

US010525472B1
United States Patent
Pandey et al.
(10) PatentNo.: US 10,525,472 B1
(45) Date of Patent: Jan. 7 , 2020
(56) References Cited
(54) DROPLET ACTUATOR AND METHODS OF
DROPLETMANIPULATION
U.S. PATENT DOCUMENTS
(71) Applicant: Iowa State University Research
Foundation, Inc.,Ames, IA (US)
8,753,498 B2
2009/0211645 Al
2012/0091003 Al
2013/0316396 A1 *
6/2014 Chuang et al.
8/2009 Bohringer et al.
4/2012 Chuang et al.
11/2013 Fricking C12M 27/16
435/41
C12M 29/00
222/55
2014/0138405 A1 *
(72) Inventors: Santosh Pandey, Ames, IA (US); Riley
Brien, Ann Arbor,MI (US); Taejoon
Kong, Ames, IA (US); Zach Njus,
Ames, IA (US); Jared Anderson, Cedar
Rapids, IA (US)
5/2014 Inoue
(Continued)
FOREIGN PATENT DOCUMENTS
(73) Assignee: Iowa State University Research
Foundation, Inc.,Ames, IA (US) WO 2010151794 A1 12/2010
(* ) Notice: OTHER PUBLICATIONS
Subject to any disclaimer,the term ofthis
patent is extended or adjusted under 35
U.S.C. 154(b)by 350 days.
(21) Appl.No.: 15/140,182
(22) Filed: Apr. 27, 2016
Related U.S. Application Data
(60) Provisionalapplication No.62/153,121, filed on Apr.
27, 2015.
(51) Int. Cl.
BOIL 3/00 (2006.01)
(52) U.S. Ci.
CPC . BOIL 3/502792 (2013.01); BOIL 2200/0605
(2013.01); BOIL 2200/14 (2013.01); BOIL
2300/123 (2013.01); BOIL 2300/126
(2013.01);BOIL 2300/165 (2013.01); BOIL
2300/166 (2013.01); BOIL 2400/0457
(2013.01)
(58) Field of Classification Search
CPC combination set(s) only.
See application file for complete search history.
Adafruit Industries, “Adafruit Motor Shield,” Adafruit Learning
System ,(2014),56 pages,https://learn.adafruit.com/adafruit-motor
shield, last updated on May 12, 2014.
(Continued)
Primary Examiner Brian R Gordon
(74) Attorney, Agent, or Firm — McKee, Voorhees &
Sease, PLC
(57) ABSTRACT
Apparatus,methods, and systemsfor automated liquid drop
letmanipulation include an open droplet supporting surface.
An actuator can translate the surface in space with at least
onedegree freedom ofmovement to influence movement of
oneormore droplets on the surface. In one embodiment,the
surface is patterned with areas that attractthe droplets and
interstitial areas that repelthe droplets to enhance transport
of droplets. For example, for water-based droplets the
attracting areas can behydrophilic and the repellinghydro
phobic. In one embodiment, the repelling areas are super
hydrophobic. Electromechanical movementof the surface
avoidsexpensiveand complex microfluidic fabrication and
components, and avoids electrowetting requirements.
13 Claims, 67 Drawing Sheets
DropletActuator Platform
32
20
22
102
:12
COMPUTER

US 10,525,472 B1
Page 2
(56 ) References Cited
U.S. PATENT DOCUMENTS
2015/0018248 A1* 1/2015 Kim B29C 45/1671
506/14
B01J 19/0046
2018/0015437 A1* 1/2018 Lammertyn
OTHER PUBLICATIONS
Elsharkawy,Mohamed , etal.,“Inkjet Patterned Superhydrophobic
Paper for Open-Air SurfaceMicrofluidic Devices," Lab on a Chip
Paper,Royal Societ of Chemistry (2014) 11 pages Jan. 6,2014.
Epson “WorkForceWF-2540” Brochure, 2 pages Sep. 1, 2012.
Kong, Taejoon, et al., “Motorized Actuation System to Perform
DropletOperationson Printed Plastic Sheets," Lab on a Chip Paper,
Royal Society ofChemistry (2016 ) 12 pages Apr. 8,2016.
Kong, Taejoon, et al., Supplementary Figures and Videos for
“Motorized Actuation System to Perform Droplet Operations on
Printed Plastic Sheets,” Lab on a Chip Paper, Royal Society of
Chemistry (2016 ) 22 pages Apr. 8, 2016 .
Chiou,Pei Yu,“LightActuation ofLiquid by Optoelectrowetting,”
Elsevier Science B.V., www.sciencedirect.com , 8 pages Jun. 1,
2005.
Rust-Oleum NeverWet Technical Data Sheet,“Moisture Repelling
Treatment,” (2015) 2 pages Sep. 2, 2015.
Bi-Polar Electric Motor Tech Sheet, date unknown.
Celia,Elena,etal.,“RecentAdvancesin DesigningSuperhydrophobic
Surfaces,” Journal ofColloid and Interface Science, www.elsevier.
com /locate/jcis (2013), 18 pages Apr. 10, 2013.
Duncombe,Todd A.,etal.,"ControllingLiquid Dropswith Texture
Ratchets,” Advanced Materials (2012 ), www.MaterialsViews.com ,
pp. 1545-1550, 7 pages Feb. 14, 2012.
Duncombe, Todd A., etal.,“Directed Drop Transport Rectified from
Orthogonal Vibrations via a FlatWettingBarrierRatchet,” Langmuir,
American Chemical Society (2012), 6 pagesAug. 30, 2012. * cited by examiner

U.S. Patent Jan. 7 , 2020 Sheet 1 of67 US 10,525,472 B1
DropletActuatorPlatform
24
22
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COMPUTER
Droplet Actuator Platform
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FIG . 2

U.S. Patent Jan. 7, 2020 Sheet 2 of67 US 10,525,472 B1
DropletActuator Platform Block Diagram
InputDevice Computer
USB
OutputDevice
105
Arduino
Microcontroller
Motor
Controller
Detector (ex.
Camera)
Stepper Motors
Droplet
Actuator
FIG . 3

U.S. Patent Jan. 7 , 2020 Sheet 3 of67 US 10,525.472 B1
Task 1 > Droplet Transport
Side View Top View
305
32
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U.S. Patent Jan. 7, 2020 Sheet 4 of 67 US 10,525,472 B1
Droplet Transport Sequence
Hydrophilic surface
Transparency file
33 ms
50ms
67ms
FIG .
Cross symbollinethickness
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FIG . 5

Droplet release angle force diagram
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Release angle vs linethickness
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Dropletretention force diagram
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U.S. Patent Jan.7, 2020 Sheet 10 of 67 US 10.525.472 B1
Task 1 > Droplet Transport
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Task 2 > Multiple Droplet Transport
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U.S. Patent Jan.7, 2020 Sheet 12 of 67 US 10.525.472 B1
Task 2 >Multiple Droplet Transport
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U.S. Patent Jan.7.2020 Sheet 15 of 67 US 10,525.472 B1
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U.S. Patent Jan. 7, 2020 Sheet 18 of 67 US 10,525.472 B1
Task 6 > Separation ofMagnetic Beadswithin Droplets
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2
DROPLETACTUATOR AND METHODS OF tact angle of droplets relative a surface, thereby changing
DROPLETMANIPULATION their wettability. This phenomenon can be used to influence
dropletmovement relative a surface. However, this gener
CROSS-REFERENCE TO RELATED ally needsexactingcalibration,hascomplexity andcost, and
APPLICATIONS 5 also requires electricalor acoustic energy at the droplets.
A need for improvement in this technical field hasbeen
Thisapplication claimspriority under 35 U.S.C.$ 119to identified by the inventors. This includes fabrication with
provisional application Ser. No. 62/153,121 filed Apr. 27, less costly techniques and components,while having sub
2015, herein incorporated by reference in its entirety. stantial flexibility and customization capabilities for a vari
10 ety of dropletmanipulation tasks.
GRANTREFERENCE
BRIEF SUMMARY OF THE INVENTION
This invention wasmade with government supportunder
No. CBET1150867 awarded by National Science Founda The present invention includes an apparatus and system
tion and No.HDTRA1-15-1-0053 from the Defense Threat 15 formanipulation ofliquid droplets in an automated fashion.
Reduction Agency. The governmenthas certain rights in the In a general aspect of the invention, an open or closed
invention . droplet-supporting surface is automatically translated or
moved in space from and back to ahomeor starting position
BACKGROUND OF THE INVENTION in a predesigned direction, speed,and amount. The transla
20 tion and return is correlated to the type andmakeup ofthe
A. Field of the Invention droplet to influence it to move in the direction of initial
translation and stay ata spaced-apart, new position on the
The presentinvention relates to automated manipulation surface. Further cycle translations and returns can influence
of liquid droplets, and in particular, to a system , apparatus, further movement in that direction. A droplet can thus be
andmethod of influencingmovement of one ormoredrop- 25 manipulated acrossthesurface,atleastin one direction,by
lets relative to a surface. simple one degree freedom ofmovement(here linearmove
mentin the planeofthe surface). The translation isdesigned
B. Problems in the Art to overcome any forces that try to keep the droplet in
position.
There is a need for efficientand effectivemanipulation of 30 One example is linear translation.Such linear translation
liquid droplets.Just a few examples are immunology,pro can be effectuated in a variety ofways. A relatively quick
tein chemistry,and biomarkeridentification.Anotherareaof movement in an in-plane direction would promotedisplace
use would be in molecular diagnostics of physiological ment of a droplet from its starting position. A quickly
samples (e.g., dried blood, urine, saliva). Handling opera following return of the surface would further promote that
tions can includesuch things as transport,mixing,merging, 35 displacement. A numberofdropletmanipulation taskscould
dispensing, and particle separation from liquid droplets. be performed,including with one droplet or pluraldroplets.
One long-usedmethod ismanualmanipulation, such as Another example oftranslation ofthe surface in space is
with hand-held pipettes. For example, a typical biological two degrees freedom ofmovement ofthe surface. This can
experiment requiring one or more operations on liquid provide for droplettransportin twodirectionsrelative to the
droplets can requiremultiple steps, such aspipetting, rins- 40 surface.Oneexample is lineartranslation in two different
ing, washing, separating, lysing, incubation, and some directions in theplaneofthe surface. Those directionscould
detection technique. Although tools and components to beorthogonal. They could be oblique. This would increase
accomplish these stepsare generally notcomplex or costly, the variety oftasksthatcould beperformed.An alternative
manual droplet manipulation can be cumbersome, time two-degree freedom of movement translation would be
consuming, and prone to human error. 45 tilting of the surface relative a single pivot point. By
Automated or semi-automated methods have been devel selection oftilting in one verticalplane (one degree freedom
oped.Many current systemsrely on automated liquid han ofmovement), a second vertical plane (second degree free
dling techniques. dom ofmovement), or some proportional combination of
Some of these systems rely on microfluidics. The fabri both, a droplet can be influenced to transport from one
cation ofsuch systemscan becostly.Many automated liquid 50 location to anotheron the surface.Relatively non-complex
handling systems can involve tens or even hundreds of components can be connected to the surface to effectuate
thousands of dollars in capital costs. Digital microfluidic two-plane tilting. In one example two electric motors could
systems can help automate atleast some ofthe steps but, be operated to tilt a platform supporting the surface in
again, they tend to be expensive. They may notbe easily orthogonal vertical planes a rangeoftiltangle and speed to
convertible between differentdropletmanipulation tasks or 55 allow tilting in any direction. This further expands the
useable in a variety ofdifferentenvironments.Forexample, variety of tasks possible. Control of motor pulley RPM
photolithography or other quite exacting fabrication tech controls the speed and amountoftilt, as well as return to
niques can implement a network of fluid pathway in a homeofthe platform .In one embodiment,thebeltscan have
substrate according to a design plan .However, once fabri atleast a section which is elastic designed to assist droplet
cated, there are inherent limitations in the variety of tasks 60 movement. The combination of amountand speed oftilt,the
that can be performed with that network. Substantially fluidic properties ofthedroplet, the hydrophobicity of the
different dropletmanipulation may require a different,and surface, and the elastic properties ofthe belts can produce a
just as costly, alternative network . jerking action that can be managed advantageously for
Another example of an automated system for liquid dropletmovementand control.
dropletmanipulation is called electrowetting.Stimulus(very 65 In anotheraspect of the invention, the surface includes a
high electrical voltages, laserbeamswith electric voltage,or predetermined pattern . In one embodiment, thepattern com
vibrations from sound-generating devices) changes the con prises areas atwhatwillbecalled dropletpositionsarranged

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spaced-apart in or on the surface. These pattern areas can be sizesof droplet location patterns to facilitate different drop
formed in predetermined shapesand sizes. Thoseshapes and lets, or different droplet motions. Themethod can use the
sizes can be the sameat each dropletposition, or different. apparatus discussed above.
In homeposition forthe surface,the shapes and sizes atthe Another aspectofthe invention comprises a system for
droplet positions are configured for the droplet type and 5 manipulating dropletscomprising an open droplet support
makeup to promote the droplet staying in a dropletposition ingsurface, an actuating sub-system to translate thesurface
until sufficienttranslation is applied to the surface to move with at least one degree freedom ofmovement, and a
thedropletfrom thatposition. Direction,amount, and speed programmable controller sub-system to control the actuator
oftranslation influences direction of dropletmovement on to accomplish a variety of droplet manipulation tasks. The
the surface. In one example, theshapes can be geometrical programming can storea wide variety ofdifferent tasks, any
(e.g. dots,circles,triangles, squares, lines,etc.). In another ofwhich can be selected foractuation. Theprogramming is
example,theshapescan be similar to typographical symbols also easily customized for new or alternative tasks.
(e.g. + orplus-signs, > or < or greater than or lessthan signs, Itis therefore a principle object,feature,aspect,or goalof
etc.). There can be other shapes or combinationsofshapes. the invention to improve over or solve problemsand defi
Size in terms of length width and thickness can vary ciencies in the art.Other objects, features, aspects,or goals
depending on the fluidic properties of the droplet, hydro ofthe invention include a dropletmanipulation apparatus,
phobicity ofthe surface,hydrophilicity of thepatterns, and method, or system which :
the operation to be performed. 1. has relatively low complexity and cost compared to
In one example, for water-based droplets, the patterned 20 digitalmicrofluidic systems;
areas of the surface can comprise hydrophilic material or 2. can be applied to a variety of droplet manipulation
etched grooves atthe droplet locations.Hydrophobic mate tasks;
can be in the interstitial areas between the droplet 3. provides flexibility regarding number and types of
locations.Such droplets are influenced to stay in place atthe tasks;and
droplet locationsby thehydrophilicmaterial untilsufficient 25 4.doesnotrequirehigh voltagesorutilization ofelectrical
translation action of the surface overcomes the attraction. or acoustic forces.
Hydrophobic areashelp promote movementofthe droplets These and otherobjects, features,aspects and goalsofthe
between droplet locations. In one example, the surface can invention willbecomemore apparentwith reference to the
bean independent,removable/replaceable,thin film orsheet accompanying specification.
thatcan beoverlaid upon amore rigid substrate or platform . BRIEF DESCRIPTION OF THE DRAWINGS
The removable patterned surface can be held in place by AND APPENDICES
electrostatic forces,adhesive,mechanicalfasteners,or other
techniques. The film or sheet itself can bemade ofhydro
phobicmaterial,or such a property can be added (e.g.a 35 trations to help present exemplary embodiments of the
Thedrawings attached after this description include illus
spray-on hydrophobic substance). The hydrophilic pattern present invention. Theinvention isnotlimited to the specific
can be inkjet printed onto the film or sheet. Alternatively, embodiments.
grooves canbecutor etched on thehydrophobic surface that FIG .1 is a perspective view ofa dropletactuatorplatform
encapsulates air pockets. This makes it easy to design and and actuatorsystem according to one example oftheinven
implementa pattern using standard typographicalsymbols. 40 tion.
Fontsize can simply be changed to increase or decrease size FIG . 2 is similar to FIG . 1 adding a coordinate system .
of the symbols. Other configurations for hydrophilic and FIG . 3 is a block diagram of a system of FIG . 1.
hydrophobic areas are, of course, possible. The use of a FIG .3-1 is a seriesofdiagramsillustrating an exemplary
removable sheet and inkjetprinting or cutting allowsa very embodiment of the open droplet supporting surface in the
cost-effective, highly flexible way to create a variety of 45 form ofa patterned removable sheet adhered to a substrate,
patterns for a variety of droplet types and tasks. Quick and and how tilting of the substrate can transport a droplet from
easy selection ofdifferentprintable shapes and sizes further one droplet position to the other on the surface.
increases the variety of droplet manipulations possible, FIG . 4 is a sequence of photographs (left side) and
including for plural droplets. The size and shape variances diagrams(right side) illustratingdroplettransportrelativeto
can influence droplets in different ways and, thus, allow 50 degree ofsurface tiltaccording to an example ofthe inven
different droplet reaction to each surface translation. This tion.
can facilitate such tasks asmoving one type ofdroplet but FIG .5 is a diagram illustrating one type ofpattern shape
leaving another type of droplet stationary. This can allow (plus signs) and variation of size (line thickness) for that
selective operations on onetypeofdroplets,such asmerging shape to promote different effects on droplets.
ormixing. This can facilitate movementofdroplets in only 55 FIG . 6 is a diagram illustrating the physics relating to
certain directions. The combination of a printable pattern, angle of surface tilt on a droplet.
relatively non-complex actuation , and open surface droplet FIG . 7 is a graph illustrating droplet release angle versus
support promote an economical yet highly flexible and line thickness in FIG . 5 .
customizable dropletmanipulation system . FIG .8 is a graph illustrating dropletrelease force versus
In another aspectofthe invention, amethod ofautomated 60 line thickness in FIG . 5.
manipulationofliquid droplets includesmovingone ormore FIG . 9 is diagrammatic views of dropletretention force
droplets on a surface by controlled translation ofthe surface relativeto a hydrophilic track at the droplet and surrounding
direction, amount, and speed, as well as return to home superhydrophobic areas.
position. This can optionally include a predetermined pat FIG . 10 is a droplet actuation force diagram .
tern of droplet locations between interstitial areas on the 65 FIG . 11 is a representation of a graphic user interface
surface for further control of the droplets. The predeter (GUI) for a controlsub-system for one exemplary embodi
mined pattern on thesurface can include differentshapesand mentof the invention.

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FIG . 12 is a photograph showing a single droplet on a FIG . 33 isa reproduction of a computerdisplayGUIsuch
tiltable platform according to the apparatus of FIG . 1. as can be used with control ofthe apparatus of FIG . 23.
FIG . 13 is a diagram illustrating a Task 1 (single droplet FIG . 34 are illustrations of operating parameters for the
transport)according to a dropletmanipulation possiblewith apparatus of FIG . 23.
the apparatus of FIG . 1. FIG . 35 are diagramsillustrating operational characteris
FIG . 13-1 is a photograph of the platform of FIG . 1 tics ofthe apparatusofFIG . 23.
relative Task 1. FIG . 36 are diagramsillustrating operational characteris
FIG . 14 is a diagram illustrating a Task 2 (multipledroplet tics of the apparatusofFIG . 23.
transport)according to a dropletmanipulation possible with FIG .37arephotos ofamixing operation for the apparatus
the apparatus of FIG . 1. of FIG . 23.
FIG . 14-1 is a photograph of the platform of FIG . 1 FIG . 38 are diagramsillustrating operational characteris
relative Task 2 .
FIG .15 is a diagram illustrating a Task 2 (multipledroplet tics of the apparatusofFIG . 23.
transport) according to a dropletmanipulation possible with FIG . 39 are diagramsillustratingoperationalcharacteris
the apparatus of FIG . 1. tics of the apparatus of FIG . 23.
FIG . 16 is a diagram illustrating a Task 3 (merging and FIG .40 are diagramsillustrating operational characteris
mixing droplets) according to a dropletmanipulation pos tics of the apparatus ofFIG . 23.
sible with the apparatusof FIG . 1.
FIG . 16-1 is a photograph of the platform of FIG . 1 DETAILED DESCRIPTION OF THE
relative Task 3 . EXEMPLARY EMBODIMENTS
FIG . 17 is a diagram illustrating a Task 4 (one directional
movementofdropletsbased on pattern shape)according to A.Overview
a dropletmanipulation possible with the apparatus ofFIG .
1. For a better understanding of the invention, specific
FIG . 17-1 is a photograph of the platform of FIG . 1 25 exemplary embodimentswillnow be described in detail. It
relative Task 5. is to be understood that these are neither inclusive nor
FIG . 17-2 is a diagram illustrating Task 4 with a different exclusive of the formsthe invention can take. Those ofskill
pattern . in the art will appreciate that the invention can include
FIG . 17-3 is a photograph of a platform relative alterna obvious variations.
tive Task 4 . It is to beunderstood thatthe exemplary embodimentsare
FIG . 18 is a diagram illustrating a Task 5 (dispensing of discussed in the contextofutilizingan economicalpatterned
a droplet)according to a dropletmanipulation possible with surface on a platform comprised of hydrophilic pattern
the apparatus of FIG . 1. shapes atdropletlocationsand hydrophobic surfaces outside
FIG . 18-1 is a photograph of the platform of FIG . 1 those dropletlocations.However,it is to be understood that
relative Task 6 . 35 with appropriatematerial technology, the invention can be
FIG . 19 is a diagram illustrating a Task 6 (separating applied to droplets that are not necessarily water-based.
magnetic particles from a droplet) according to a droplet
manipulation possible with the apparatus ofFIG . 1. B. Exemplary Embodiment 1
FIG . 19-1 is a photograph of the platform of FIG . 1
relative Task 6 . FIGS. 1-22 feature one exemplary embodiment of a
FIGS. 20-1 to 20-20 are photographsofthe apparatusof dropletmanipulation system according to the presentinven
FIG . 1 from different perspectives. tion. Aswillbe appreciated by those skilled in the art,this
FIGS.21-1 to 21-6 are computer-assisted drawingsofthe is but one form the invention can take.
apparatusofFIG . 1 from different perspectives. 1.General Apparatus and System
FIGS.22-1 to 22-5 are illustrations of thepivot post and 45 With particularreferenceto FIGS. 1-3,11,21-1, and 22-1
universaljoint of the apparatus ofFIG . 1 thatallow tilting to 22-9, thebasic components for a system 10 according to
oftheplatform in any direction. the invention can be seen. More details will follow .
FIG . 23 is a perspective view of the apparatus of FIG . 1
with an enlarged photo of droplets on its surface. a. Tiltable Platform
FIG . 24 is a diagrammatic view and correlated photos of 50
dropletmovement on the apparatus of FIG . 23. A surface to support one or more droplets in an open or
FIG . 25 is top plan view ofthe surface ofthe apparatusof closed environmentcan be a platform that can be planar.As
FIG . 1 illustrating differentdropletmanipulations. shown in FIG . 1,system 10 provides two degree freedom of
FIG . 26 is atop plan view showing otherdropletmanipu movementofa platform 20by suspending platform 20 on a
lations. 55 verticalpost extending from abase 12. The post includes a
FIG .27is a top plan view showing otherdropletmanipu firstportion 14,a hand ortransition 16 ,and a universaljoint
lations. 18. Platform 20 mounts onto u-joint18 to provide a single
FIG .28 is a topplan view showingother dropletmanipu pivotpointforplatform 20 relativeto a verticalaxis(e.g.the
lations. Z-axisofFIG .2).In thisexample,the pivotpointisbasically
FIG .29 is a topplan view showingother dropletmanipu- 60 centered underneath theplatform . An alternative to an open
lations. supporting surface such as FIG . 1 could be the addition of
FIG . 30 is a perspective view ofdroplet placementon the a hydrophobic top plate in contact with thedroplet (closed
surface of the apparatus ofFIG . 23. system ).
FIG . 31 is a top plan view showingotherdropletmanipu There arealternativewaysto tilt a platform . There are also
lations. 65 alternativeways to translate a surface.One example is linear
FIG . 32 are graphsillustrating aspectsof operation ofthe translation. The shape and size of the platform can vary
apparatus of FIG . 23. according to need and desire.
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b . Actuators of Platform Tilt control of direction,speed, and amount of tilt to promote
movement from droplet(s). Microcontroller 105 also con
An actuation sub-system translates the platform . In the trols reversing direction ofbelts 101 to return the platform
example of FIG . 1, two electricmotors 104,each which can from tilt back to home or horizontal. This, with the elastic
rotate a toothed pulley 102, aremounted on thebase 12. The 5 connections, can add a “ jerking” type action to further
rotational axes for pulleys 102 are at 90 degrees to each promote dropletmovement.
other in a plane parallel to the home (horizontal) position Pulley diameter and the RPM and length ofoperation of
plane of platform 20. Each motor 104 drives a belt 101, themotor axle substantially determine speed and amountof
having complementary teeth to its respective pulley. Each
belt 101 is connected atopposite endsto connection lugs24 10 platform tilt (and subsequentreturn ). This can be correlated
on the bottom of platform 20 (see also FIG . 22-4 ). to the amount of supplemental jerking action on the plat
As illustrated in FIGS. 1 and 2, one belt 101 is connected form . As will be appreciated by those skilled in the art,
atopposite sides ofplatform 20 along a first verticalplane motors 104, belts 101, and elastic connections 103 can be
through the pivotpointofplatform 20 (e.g.the X/Z plane of selected to have, in combination, the desired forces, aswell
FIG . 2). The other belt 101 is connected at opposite sides 15 as amount of tilt.
along the second vertical plane orthogonal to the first and
through that samepivotpoint(e.g.the Y/Z plane in FIG .2). e . Patterned Surface of Platform
In this embodiment, the opposite ends ofeach belt 101
comprise elastic sections 103. These sectionsprovide elas
tomeric propertiesto thebelts,which willbe discussed later. 20 Enhancement of the platform surface can enhance per
Ties 65 and 67 (e.g. zip ties) can clamp the elastic section formance of dropletmanipulation. An optional implemen
between a platform lug 24 and an end of belt 101, as tation ofthe dropletsupporting surface,and a feature ofthis
illustrated in FIG . 21-1. Other types of elastic sections and embodiment, is separate, removable sheet 30 carrying a
attachment techniques are,ofcourse, possible. patterned surface 32. Sheet 30 can be adhered to the top of
Other types of actuation sub-systems are possible. The 25 platform 20 (see FIGS. 1and 3-1).To promote droplet(s) to
electric motors and belts provide a non-complex, economi stay in position on theplatform ,this independent,removable
cal technique. Also,sufficientaccuracy and precision oftilt sheet 30 on top ofplatform 20 has the following character
can be accomplished with commercially available stepper istics.
motors and control circuitry.An advantage ofthis embodi A hydrophobic layer 304 (FIG . 3-1) can be created across
ment is that precision and accuracy do not have to be 30 the surface of substrate 303 (which can be platform 20).
exceedingly high for effectivenessoftheprinciples of opera
tion over the range ofneeded tilt angles. Hydrophilic material (plus-sign or + shapes 305 in the
example in FIG . 3-1) can be printed,deposited, embossed,
c . Pivot Axis for Platform added,orotherwise created atspacedapart locations andbe
35 ofa hydrophilic nature relative thedroplet(s). Alternatively,
Platform 20 is basically tensioned in homeorhorizontal shapes can be etched or cut in the hydrophobic layerusing
position on the pivot axis created by thepost and universal a cutter or chemical etching process. These techniques are
jointby thebelts and elastic connections. FIGS. 22-1 to 22-4 known to those skilled in the art. Therefore, as illustrated in
show how bottom post member 14 (FIG . 22-2) can be FIG . 3-1,a dropletwilltend to remain andbeattracted to a
screwed (see screw 15) or bolted or otherwise fastened to 40 hydrophilic shape,whereas ifitismoved offofoneofthose
hand or transition member 16 (FIG . 22-3). The top 17 of shapes by tilting action, it is influenced to release,move
hand 16 is a square head that complementarily fits into easily across the hydrophobic area, and then stop at an
socket55 in bottom u -joint piece 56 (FIG . 22-1). A center adjacenthydrophilic shape.
lug 27 on the bottom of platform 20 (FIG . 22-4) is a For example, tilting of the platform 20 (in FIG . 3-1
complementary square shape to fit into thesocket51 in top 45
piece 52 of u-joint 18 (FIG . 22-1). In this way, u-joint 18 platform 20 is a combination ofsubstrate 303,hydrophobic
pieces 52, 54,and 56 connect platform 20 to base 12 but layer 304,and interspersed hydrophilic shapes 305)downto
allowstilting of platform 20 around either pivot pin 53 or the right (relative to the viewing direction of the page of
pivotpin 57 ofthe u-joint,orboth (see FIGS. 22-1 to 22-5 ). FIG . 3-1) a sufficient amountallows gravity and any added
Thisprovides two degree freedom ofmovementofplatform 50 jerking action to promotemovementof thedroplet301 away
20 in two vertical planes (X/Z and Y/Z ). Further,it allows from a first hydrophilic +-shape 3025 acrossthe interstitial
tilting ofplatform in any direction relative the vertical axis hydrophobic surface 304, and to the next adjacenthydro
Z through u-joint 18 depending on direction ofrotation of philic +-shape 305. Return of platform 303 to horizontal
motor pulleys 102. The direction and amount of pulley would promote the droplet then staying in thatnew position.
rotation determines notonly direction of tilt but amountof 55 Aswillbe illustratedby the additionaldetails that follow,
tilt. In this embodiment, the amountof tilt needed is in the and specific examplesofdropletmanipulatingtasksthatcan
approximate rangeof3 to 4.5 degrees in any direction from be accomplished, the shape and size of the hydrophilic
horizontal.
Alternative platform pivot techniques are possible. droplet position patterns can vary according to need or
desire. Those parameters can affect how much tilt and
a. Programmable Controller jerking action is needed to achieve differentmanipulations
in droplets.
Controlofplatform movement is with a controller sub Aswillbeappreciated by those skilled in the art, empiri
system . A programmable controller (e.g. microcontroller cal testing can help optimization ofcertain oftheprocesses
105) with associated interface circuitry (e.g.motor control 65 or operations.Likewise, such testing can assist in determin
circuit 106) to themotors 104 allows automation of amount ing preferred shape and size of certain ofthe hydrophilic
and direction oftilt of platform 20. Essentially,this allows droplet locations.
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C. Specific Details of Embodiment 1 to the free ends of each belt and fixed to the upper
platform by a stainless steelhose clamp or zip tie. The
1) Introduction elastomeric rubber tubing 103 ensures adequate belt
This contains a detailed description of the invention in its tension for thepulley system .FIG . 2 showsa full-color
current form , based on a prototype device, as well as a image of the droplet actuator platform system 10.
discussion ofthe generalprinciplesofoperation.In addition, The block diagram in FIG . 3 illustrates the connectionsof
alternative configurations of the system are proposed and the communication and controlsystem . The user can
envisioned which could offer similar or extended capabili interact with the device using a computer system 40
ties (ex.oleophobic coatings foroildropmanipulation). This with inputdevice(s)42 (keyboard,mouse,GUI,touch
description will refer to the Figures summarized above 10 screen, etc.) and output device(s) 44 (monitor,speak
including thematerials listed below : ers, etc.). The computer 40 communicates with an
1 High-resolution photographs of the device from several Arduino microcontroller 105 through a USB connec
angles (FIGS. 20-1 to 20-20). tion using software described in Section 4, below . The
2.3D Computer-aided design (CAD )models of the device Arduino microcontroller 105 communicates with the
(FIGS. 21-1 to 21-6). steppermotor controller circuit 106 , which drives the
3. Technical information of the components used in the stepper motors 104 with the appropriate voltage and
device (specification sheets, datasheets, etc.) current(~ 12V,350mA).Bydefault,the steppermotors
4.Selected framesof videosof device operation and droplet 104 remain stationary. Using the computer interface, a
operations. steppermotor 104 can be commanded to rotatewith the
2) Droplet Actuator Design following three parameters: number of steps (1.8º per
The droplet actuator 10 includes two main components,a step ), stepping speed (0-200 revolutionsper minute),
mechanical control platform , and a droplet manipulation and step direction (forward ,reverse ). The belt system
surface. The control platform 20 is able to rotate about two linksthesteppermotorpulley 102to theupper platform
axes,tilting up/down,left/right,oranycombinationofthese. 30 of the droplet actuator. As the upper platform
The dropletmanipulation surface includes a superhydropho- 25 measures 10.2 cm , and thediameter ofthepulley is 1.2
bic substrate 30 or 304 patterned with hydrophilic areas 32 cm ,the effective gear reduction between themotor and
or305.Water-based droplets adhereto thehydrophilic areas, the platform is 1:8.5. This means each step of the
but by rapidly tilting the control platform , droplets can be stepper motor corresponds to a 0.21° rotation of the
transported from onehydrophilic area to another.Modifying upper platform . A camera 46 provides feedback to the
the configuration ofthe hydrophilic regionsenables various 30 computer aboutdroplet position and color.Monitoring
droplet operations to be performed, including transport, theposition and colorof each dropletallowsautomated
mixing,merging, dispensing,and particle separation. manipulation and readoutof colorimetric tests. Such
i) Mechanical ControlPlatform software is commercially available.
The droplet actuator 10 (FIG . 1) consists of a planar ii) Parts List
platform 20 thatismechanically rotated abouttwoaxes 35 1.Plexiglass (platform 20, base 12,post 14/16)
on a central pivot 100. The desired rotation is accom 2.2x Steppermotor (104)
plished by two electricalmotors 104. Each motor is 3. AdafruitMotor/Stepper/Servo Shield (105/106)
connected to the platform with a belt 101, pulley 102, 4. Timing Beltx2 (101)
and elastomeric rubber tubing 103. A computer pro 5.2x Aluminum GT2 Timing Pulley (102)
gram communicates with microcontroller 105 (e.g. 40 6.2x Stepper MotorMount
Arduino Microcontroller)which controls each motor 7.Universal Joint(18/100)
via a motor control circuit 106, specifying the fre 8.8x Hose Clamp (65/67)
quency of rotation (or revolutions per minute), and 9.Elastic rubber tubingx4 (103)
duration of operation. Proper coordination of these iii) DropletManipulation Surface
parametersbetween thetwomotors enables thedesired 45 Referring to FIG .3-1,thedroplet actuator10also consists
rotation of the platform . ofa film ortransparency 303adhered to the top surface
The structure consists ofthreemain components:an upper of the abovementioned planar platform 20 in FIG . 1.
platform 303, a verticalsupport column 14/16/18, and The surface of the film 303 is first coated with a
a base 12. The upper platform is connected to the superhydrophobic (i.e.water repelling) chemical coat
vertical column through a universal joint 18, which 50 ing 304, and then specific hydrophilic 305 (i.e.water
allowsthe upper platform to pivot about two axes. The attracting) patternsare printed on the superhydropho
upper end ofthe universal joint fastened to the center bic-coated film using an inkjet or laser printer to
oftheupperplatform bypress-fitting into lug 27). The accomplish various tasks of droplet manipulation. In
lower end ofthe universaljointis also press-fit to the this embodiment the hydrophilic material is black
vertical support column (square head 17). Epson inkjet printer ink (model T200XL120). Others
The base 12, consisting of a square plexiglass sheet are possible.
measuring 25 cmx25 cmx5 mm , is attached by screw The specific hydrophilic patterns are dependent on the
to the vertical column (at piece 14). The vertical task of dropletmanipulation to be accomplished. We
column measures 8 cm tall and the upper platform conducted rigorous characterization to select the best
measures 10.2 cmx10.2 cmx1.2 cm . Two stepper 60 patterns for each task, but other patterns may also
motors 104 and an Arduino microcontroller 105 with a perform any given task. Other symbols thatmay be
stepper motor controller circuit 106 are fixed to the used include, but are not limited to, solid circles,
base with aluminum mounting brackets and double hollow circles,crosses,solid squares,hollow squaresor
sided tape, respectively. Each edge ofthe upper plat any otherphotographic, alphanumeric or other charac
form is connected to a timing belt 101 which is driven 65 ters.
by a pulley 102 attached to each steppermotor's shaft. Two methods of fabricating superhydrophobic surface
A piece ofelastomeric rubber tubing 103 was attached were tested for use with the current system . The first
55

phobic
5
10 6
8
10
20
30
200
110-130
90-130
80-120
70-120
50-110
10-30
120
110
90
70
50
20
10-15
10-16
11-17
11-15
9-18
8-15
10
11
12
14
15
15
6
8
10
20
30
200
110-130
100-130
90-130
80-120
120
110
100
90
80
30
11-16
11-16
11-17
11-17
9-18
8-15
13
13
14
15
17
13
20
20-40
25
6
8
10
20
30
200
140-150
130-150
100-130
80-120
60-110
30-60
150
150
110
90
80
50
13-16
13-16
11-16
11-18
9-18
9-16
15
15
15
16
17
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method utilizes a commercially available superhydro TABLE 1
spray called Neverwetby Rust-Oleum , Vernon Typical droplet actuation parameters
Hills, Ill. 60061, USA , which creates a surface with
Size of
contact angles over 165° and roll-offangles less than droplet Revolutions perminute Number of steps
1º. TheNeverwet spray was applied to a letter-paper
(UL) Range Typical Range Typical
sized transparency sheet. See technical data sheet for
more details at http://www.rustoleum.com/~/media/ Cross symbol line thickness 0.006 in.
DigitalEncyclopedia/Documents/RustoleumUSA/
TDS/English/CBG /NeverWet/ROC-12_NeverWet_
Moisture_Repelling_Barrier_TDS.ashx. The second
superhydrophobic surface was fabricated by sanding a
LDPE plastic sheet with sandpaper (360 grit). The (4 symbols)
Cross symbol line thickness 0.008 in.
surface produced lower contactangles and higher roll
off angles, demonstrating lower hydrophobicity than
Neverwet. Forthis reason,Neverwet was chosen as the
preferred superhydrophobic surface for this embodi 60-110
ment. Other superhydrophic chemical coatings can be
used such as Teflon or paralyne. (4 symbols)
Cross symbol line thickness 0.009 in.
Similarly, fourmethods of creating hydrophilic patterns
were tested including inkjet printing, cutting, laser
printing, and pen writing. Ofthese methods, inkjet
printing produced the highest resolution and longest
lasting hydrophilic patterns. The dropletmanipulation
surfaces shown in following figures were fabricated (4 symbols)
using inkjet-printed patterns on a Neverwet coated 30 1 step = 1.8 degree in motor (0.21 degree in a top substrate)
transparency sheet. One example of such an inkjet Distance between two symbols are 0.335 cm
printer is a model WorkForce WF-2540 available Allthe valuesofRPM and stepsare also affected by thehydrophobicity ofthe surface and
the hydrophilicity of ink patterns.
from Epson America, Inc., Long Beach, Calif. 90806, 1mL (1000 ML) size droplet can betransported using 16 symbols (20 rpm and 10 steps).
USA, with details at http://www.epson.com/cmc_u 5 uL size dropletcan be transported using a single symbol (140 rpm , 11 steps).
pload/pdf/brochure_wf2540.pdf.
FIG . 4 shows the movement sequence which allows The droplet release angle was measured by slowly
droplet transportbetween two cross symbols. Images increasing the tilt angle until the droplet rolled off the
from the left side of the figure were captured from platform . The results ofthis test are shown in Table 2. By
high-speed video,while the rightsideshowsan illus- 40 forceexertedbythehydrophilic ink patternsonthedroplet.
measuring the release angle, it is possible to calculate the
trated schematic. Initially,att= 0 milliseconds (ms.), the
platform ishorizontaland thedroplet isatrest. Att=33 The diagram shown in FIG . 6 showsthe force diagram , in
ms., the platform is rotated to its highest angle (~3º which theholding force is given by the following equation:
4.59),then at t=50 ms., the droplet begins to detach F =mg sin(0)
from the initial cross symbol as the platform returnsto 45
horizontal. At t=67 ms., the droplet attaches to the The results are also plotted in FIGS. 7 and 8, illustrating
neighboring cross symbol and oscillates for approxi that thicker lines produce a greater force on the droplet.
mately 500 ms.before remaining still.
iv) Parts List TABLE 2
1.Transparency Film (303) Droplet release angle
2.Superhydrophobic coating (304) Cross symbol line thickness
3. Inkjet printer 0.006 in . 0.00 in .
The line thickness of each cross symbolcan be modified 55 Angle Angle Angle
to change the angle and rotation speed necessary to (degrees) (degrees) (degrees)
actuate a dropletof a given volume. Table 1 showsthe 20 uL 15.5° 18.6 °
typical values and range of values that successfully 11.0 ° 17.5 °
actuate droplets between 6 uL and 200 uL. FIG . 5 9.2° 11.2 °
shows the relative thickness ofeach cross symbol. The 60
range ofdropletvolumesthatcan be transported on the
platform is 5 uL to 1000 uL. These values are relative The retentive force on the droplet under similar conditions
to a variety of fluid-based droplets with or without was derived by Elsharkawy et. al. See Elsharkawy, M.,
molecules including physiological fluids such as blood, Schutzius, T. M., & Megaridis, C.M. (2014). Inkjet pat
urine, saliva, or suspensions or solutions of the same. 65 terned superhydrophobic paper for open-air surfacemicro
One feature ofthe invention is thatsystem 10 canbeset fluidic devices.Lab on a Chip, 14 (6 ),1168-75.doi:10.1039/
up and used for a variety ofdifferent droplet types. c31c51248g, including SupplementalInformation related to
35
50
0.008 in .
14.1 °
30 UL
40 UL 12.9 °

5
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20
cose
?
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US 10,525,472 B1
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this publication, all ofwhich is incorporated by reference provide range ofmotion,speed,and power to translate
herein . platform 20 sufficiently for these purposes.
The results are shown below . ii) Droplet Manipulation Surface
The retentive force FR of a spherical droplet on a solid The current system uses a superhydrophobic surface
surface is given by patterned with hydrophilic regions to controlactuation
ofwater-based droplets.Severalmethodsoffabricating
FR=F,-F. superhydrophobic surfaces have been developed,
including lithography,pattern templating, sol-gel, elec
Where F, is the receding end force and F, is theadvancing trospinning, layer-by-layer technique, etching, chemi
end force on the droplet Fa=2Ry cos0a And, cal vapor deposition, electroless galvanic deposition,
anodic oxidation,and electrochemical deposition.See
Celia, E., Darmanin, T., Taffin de Givenchy, E.,
Fr = f*Rycosocospd Amigoni,S.,& Guittard,F. (2013).Recentadvancesin
designing superhydrophic surfaces. Journal of Colloid
and Interface Science, 402, 1-18. doi: 10.1016/j.j
cis.2013.03.041, incorporated by reference herein.
Where R is the droplet radius, y the surface tension of the Methods of patterning hydrophilic areas include lithog
liquid,o the azimuthalanglethat circumnavigatesthe drop raphy, laser machining, etching, coating with self
let contact line from therearmostpoint (p =0)to the side of assembled monolayers (SAM ), oxides, or biomol
the drop (o =1/2) ecules,and plasmaetching.Appropriatepatternscan be
created at least in three ways: First, a hydrophilic
coating could be selectively applied to a superhydro
-cose /a + phobic surface,ora superhydrophobic coatingcould be
1/2 1/2 selectivelyapplied to a hydrophilic surface.Second,the
surface could be chemically modified to produce
cose hydrophilic regions on a superhydrophobic surface or
superhydrophobic regions on a hydrophilic surface.
Third, the surface topology could be altered to create
Where Fal is theadvancing force contribution by thehydro the appropriate pattern .
philic track, Fa2 the advancing force contribution by the The large contrast in droplet adhesion between the supe
superhydrophobic paper rhydrophobic and hydrophilic areas enables thedroplet
3) Principles of Operation actuator to operate using relatively smalltilt angles and
The dropletactuator system 10relies on two forces to drive speeds (rpm ). Using merely hydrophobic/hydrophilic
dropletmovement.Asshown above,gravitationalforce acts patterned surfaces would perform similarly with
upon the droplet,causing droplet release at relatively large 35 increased tilt angles and speeds. Oil based droplets
angles (~90-20°). Under normal operation, however, the could be actuated using patterned oleophobic surfaces.
upper platform is rotated to angles from ~ 3° to 4.5º. The Any surface upon which the liquid experiences a con
rapid movementofthe platform allows thisreduction in tilt trast in surface tension can be actuated.
angle by providing additional force which acts on the Alternatively, the droplet actuator could use an unpat
droplet. FIG . 10 shows the forces that provide droplet 40 terned hydrophobic or superhydrophobic surface to
actuation as seen from the side view of theplatform . The tilt actuate the droplets. In this case, tilting the platform
angle (0) is exaggerated for illustration. The axis ofrotation would induce dropletmotion after exceeding the drop
lies 3 cm below the platform (the radius (r) of the circle letrelease force given in the previous section.Unpat
shown). The distance of the droplet from the centerof the terned surfaces have limited ability to merge separate
platform is shown as distance (d). The radius the droplet 45 droplets,as droplets with identicalmass have identical
travels is given as (R ). release angles.
See AnalyticalModel Section, infra, formorediscussion. Another alternative to patterning hydrophilic areas is to
4) Alternative Configurations: alterthe geometry ofthe surface.By creating indenta
i) Mechanical ControlPlatform tions, sidewalls, channels, creases, or holes in the
The current system relies on a universal joint to provide 50 surface, the system could manipulate either liquids or
two-axis rotation ofthe upper platform .Othertwo-axis solid objects. For example, embossing shallow, circular
linkages could be used, including ball joints, dual indentations in the superhydrophobic surface would
hinges,or flexible rods or tubes. Platformswith higher create "wells” in which the dropletwould rest.Upon
orlowerdegrees-of-freedom (DOF) could also beused. tilting theplatform , thedroplets could be transferred to
For example, a Stewart platform using six prismatic 55 a neighboringwell.Bymodulatingthewidth anddepth
actuators provides 6 DOF comprising three linear (x,y, of thewells, different droplets could bemerged and
z)movements,and 3 rotation (pitch, roll, yaw )move mixed .
ments. Robotic arms, gimbals, and optical alignment 5) Droplet Actuator Software
multi-axis tilt platformscould also providetherequired a) Current System
tilting motion. i) Software and FirmwareRequirements
The current system utilizes rotation to provide droplet Matlab 2011b or later
actuation, but linear motion could provide similar ArduinoIO package
actuation. Translatingthe platform horizontally before Arduino Motor shield firmware
stoppingor reversingdirection would produce thesame Arduino Uno USB drivers
forcesdescribed above,without the gravitational force 65 ii)Graphical User Interface (GUI)
cause by tilting theplatform . A variety of linear actua One example of a GUIthat could be used for system 10
tors are commercially available which shouldbeableto is shown in FIG . 11. As is well understood by those
60

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US 10,525,472 B1
15 16
skilled in the art, user control could take other forms, symbols) increase the hydrophilic surface area and can
not only different GUIs and options, but different hold the droplet over higher range of actuation (FIG .
input/controlmethods. The followingrefer to reference 15).
numbers in FIG . 11: Whereas, plus symbols with thinner lines 502 can only
151: A usercan type a communication portnumber and 5 hold the droplet over a smallerrange of actuator (FIG .
connect the Arduinomicrocontroller to thecomputer. 15 ).Droplets thatneed to be stationary 504 are posi
152: A user can enter the rotation speed (rpm ) and tioned over plus symbols with thicker line widths,
number of steps the steppermotorwill turn in the x while droplets that need to be transported 505 are
and carried over plussymbols with thinnerline widths.
directions.
? iii)Merging and Mixing Droplets
153: Double arrow buttons make a top substrate tilt in 6) Task 3>Merging and Mixing Droplets: This task
one of four different directions according to the describes thejob ofautomaticallybringing onedroplet
inputs in 152. The platform does not return back to
horizontal (initialposition). to come and unite with a second stationary droplet
(FIG . 16 (diagram )and FIG . 16-1 (photo)),followed by
154 : A user can enter the forward and backward rota a method to mix the contents ofboth droplets. Using
tionspeed andnumber ofsteps ofthesteppermotors. the plus symbols discussed in previous tasks,we can
155: Single arrow buttons make the top substrate tilt bring one droplet 601tomergewith a second stationary
and return to the initial position according to the droplet602 (FIG . 16 ). This is followed bymixing the
inputs in 154. Under typical settings, the initial contents ofthemerged larger droplet603bymoving it
rotation speed is 100 rpm during the initial tilt from 20 in a circular trajectory multiple times (the number of
horizontal (0 degrees) to 3.5 degrees. The return revolutions depends on the size and diffusibility of
speed is typically setto a lowerrpm value (~20 rpm ) particles suspended in the droplets).
toprovide a slowertransition from 3.5 degreesback iv) One DirectionalMovement of Droplets
to horizontal (0 degrees). 7) Task 4>One-directional Movement of Droplets: This
156: A circular button makes a substrate return to the 25 task describes the job of automatically moving one or
initial position when the Arduino microcontroller is multiple droplets only in one direction (FIG . 17 (dia
connected to the computer. gram ) and FIG . 17-1 (photo)).Using thecrosssymbols,
157: Video Controlsbuttonsallow a user to takeimages wecanmakeone dropletstationary to a certain position
and videosof the droplet actuation through the web irrespective of the planar platform tilting in other
directions within the 150 r.p.m.rate of acceleration
FIGS. 17 and 17-1.Using a single V -shaped symbol
FIG . 12 is a photograph of a prototype platform 20 with 701, we can restrictthemovement of a single droplet
patterned surface 30/32and a singleblue droplet.For further in a certain direction, and thisdroplet is invariantto any
understanding of the invention, several specific droplet tilts in this direction FIGS. 17 and 17-1. Using another
manipulations or“ tasks” willnow be described,with refer symbolthatcomprisesthree V-shaped symbols,we can
ence to FIGS. 13-19 and subparts. restrict the movement ofsingle droplets to only one
6)DropletOperations direction, which are invariant to tilts in any other
a) CurrentSystem direction FIGS. 17-2 and 17-3.
i) Droplet Transport v) Dispensing of Liquid from Droplets
4) Task 1>Droplet Transport: This task describes the job 40 8) Task 5>Dispensing ofLiquid from Droplets: This task
ofautomaticallymoving a single droplet 301 from one describes thejob ofdispensing a fixed amountofliquid
location on the platform to another location of the from droplets by utilizing dot symbols as shown in
platform . See FIG . 3-1.Here we accomplish this task (FIG . 18 and FIG . 18-1). This task is particularly
byusing 'plus-shaped 302symbols (linewidth =0.2032 valuable when wewantto distribute one large droplet
mm , spacing between symbols=3.35 mm ) shown in 45 of sample to a number ofsmaller droplets for dilution
FIG . 3-1.Othersymbolsmay be used for this transport or various chemicalreactions. By varying the size of
task , such as solid circles,hollow circles, crosses,solid dot symbol 801, we can control the volume of the
squares, hollow squares or any other pictographic or sample dispensed on each dotsymbol (FIG . 18 ).
alphanumeric symbols. We have successfully trans vi) Separation ofMagnetic Beadswithin Droplets
ported up to 54, of food dye solution usingmovement 50 9) Task 6 >Separation ofMagnetic Beadswithin Droplets:
on single plus symbols shown in FIG . 3-1. For trans This task describes the job of separating magnetic
porting largervolumes 306 shown in FIG .13 (diagram ) micro-or nano-scale beads suspended in droplets using
and FIG . 13-1 (photo ), sets of two or more plus an external permanent or electromagnet as shown in
symbols may be used as shown in FIG . 13-1. FIG . 19 and FIG . 19-1. This task is valuable when we
ii) Multiple Droplet Transport want to separate specific particles of interest (for
5) Task 2>Multiple DropletTransport:This task describes example,antigens, proteins or other biomarkers) from
the job ofautomaticallymovingmore than one droplet biological fluid using commercially available magnetic
401 simultaneously in the same direction (FIG . 14 beads tagged with the complementary particle (for
(diagram ) and FIG . 14-1 (photo))ormoving one drop example, antibody).
letwhile keeping the others stationary (FIG . 15 (dia- 60 Using theplus-shaped symbols,weshowed thata droplet
gram )).Using the plus symbols described in Task 1, with suspendedmagnetic particles 901can beexposed
canmovemultiple droplets simultaneously where each to a permanent or electromagnet 902 (magnetic
dropletcan initially bepositioned in separated rowsor strength around 0.4 Tesla). Then by tilting the planar
columnsor in the samerow orcolumn.Formoving one platform , the liquid droplet moves away while the
dropletwhile keeping the otherdroplets stationary,we 65 magnetic particles suspended in a small volumeofthe
used plus symbolswith two ormore line width thick drop are left at the magnet's original location. The
nesses.We observed thatthickerlines501 (in the plus process can be repeated multiple times to bring the
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US 10,525,472 B1
17 18
original or a new droplet to mix with themagnetic 7) Parts List
beads,andre-separate. The system may beexpanded to a) Mechanical ControlPlatform
include multiple permanent or electromagnets posi 1. Plexiglass: was used to make a structure of base,
tioned above or below the planar platform to accom vertical column and top substrate.
plish multiple steps of particle separation, washing, 5 2. Stepper motor— NEMA-17 size — 200 steps/rev, 12V
350 mA (Adafruit, product ID : 324):
re-washing,mixing with another buffer/s,and re-sepa a.200 steps per revolution, 1.8 degrees/step (Approxi
ration. mately 0.21degree applied to the top substrate)
vii) Alternative Configuration b. Product webpage: http://www.adafruit.com/prod
Somerefinements in our approach are ongoing and men ucts/324
tioned below : Technical datasheet: http://www.adafruit.com/
a) We envision other combinations of superhydropho datasheets/12vstepper.jpg* (incorporated by refer
bic andhydrophilic printedpatterns. There aremany ence herein ).
chemicalsavailable thatcan bepurchased and tested. 3.Arduino Uno Microcontroller (Arduino)
b) We envision ways of dispensing at least smaller a. Product webpage: http://store.arduino.cc/product/
droplets.Webelieve the system is applicable to some A000066 (incorporated by reference herein ).
4.AdafruitMotor/Stepper/Servo Shield for Arduinokit
range of droplets larger also. v1.2 (Adafruit,product ID : 81) (incorporated by refer
c) We envision there will be ways to split a larger ence herein ).
droplet into smaller droplets by forcing the larger a. Product webpage: http://www.adafruit.com/prod
droplet on a sharp hydrophobic surface ormaterial. 20 ucts/81 (incorporated by reference herein).
d) We envision use in molecular diagnostics that use b. *Datasheet incorporated by reference herein.
ELISA Kits and have relevant biological samples 5. Timing Belt GT2 Profile2mm pitch — 6 mm wide
(e.g. infected blood samples). 1164mm long (Adafruit, product ID : 1184)
Advantages of our method over existingmethods (see a. Product webpage: http://www.adafruit.com/prod
discussion earlier andbelow ), such as the three catego- 25 ucts/1184 (incorporated by reference herein ).
ries ofmethods formanipulating droplets.We feelour 6. Aluminum GT2 Timing Pulley— 6 mm Belt - 20
Tooth — 5 mm Bore (Adafruit, productID : 1251)
method hasthe following benefits over these existing a. Product webpage: http://www.adafruit.com/prod
methods: ucts/1251 (incorporated by reference herein )
a)Noneed formicroelectronic fabrication: In all three 7. Stepper Motor Mount with Hardware NEMA-17
existing approaches, electrodes or textured patterns Sized (adafruit, Product ID : 1297)
are fabricated using silicon microelectronics fabri a. Product webpage: http://www.adafruit.com/prod
cation techniques, which are expensive and labor ucts/1297 (incorporated by reference herein ).
intensive.Ourmethod can include spraying a super 8. Universal Joint Kit Stanley 85-727 3 Piece (Stanley,
ModelNo. 85-727)
hydrophobic coating on a transparency and printing a. Productwebpage:
patterns using an inkjet printer, or othertechniques http://www.stanleytools.com/default.asp?TYPE=
that are less complex and cheaper. PRODUCT& PARTNUMBER =85-727 (incorpo
b ) Cheapermaterials cost: The cost of fabricating and rated by reference herein ).
assembling a digital microfluidic platform is 9. Hose Clamp: Breeze Aero-Seal 100 10H 9/16/11/16
upwards of $2000. In comparison, the cost of the inch Range 9/16" 301 SS Band (Breeze Industrial
describedprototypeoftheinvention is less than $50. Products)
Themain costs are that oftwomotors ($ 12 each) and a.Productwebpage:http://www.hoseclampkings.com/
theArduino microcontroller($15). The dramatically prod-21-1-258-107/breeze-aero-seal-100-10h-9-16
lowercostswillbe appealing forapplicationsin rural 1-1-16 -inch-range-9-16-301-ss-band.htm (incorpo
testing or clinicaltests in non-clinical labs. rated by reference herein ).
c) No high voltages required: In electrowetting, a 10. Elastic rubber tubing Resistance Band Set (Walmart)
voltage stimulus of over 150 Volts is needed to b ) Droplet Manipulation Surface
actually move a droplet. If the insulator is thicker, 1. Transparency Film Staples 50 Pack Transparency Film
voltagesashigh as300-400 voltages areneeded. The for Inkject Printers (Staples, Item : 954143, model:
companies that have adopted electrowetting have 50 23247)
found ways to add a high-voltage amplifier to their a. Product webpage: http://www.staples.com/Staples
system . In our case, the only 9 volts voltage is 50-Pack-Transparency-Film -for-Inkj ect-Printers/
needed to tilt thedroplet actuator.Such 9V batteries product_954143 (incorporated by referenceherein).
are available commercially,which helps in making 2. Superhydrophobic coating Rust-Oleum NeverWet
our system portable. (Rust-Oleum )
We have demonstrated the successful manipulation of a. Product webpage: http://www.rustoleum.com/prod
droplets on our droplet actuator. uct-catalog/consumer-brands/neverwet/neverwet
Weenvision use ofourinvention in molecular diagnostics kit/* PDF file attached in folder (incorporated by
of human samples or animal samples. Our general reference herein).
method is independent of any specific application. 60 3. Inkjet printer Epson WorkForce WF-2540 All-in -One
Certain types of patterns can be printed depending on Printer (Epson,Model: C11CC36201)
specific experiment under study. a. Product webpage: http://www.epson.com/cgi-bin/
The field ofmolecular diagnosticsusing newer technolo Store/jsp/Product.do?sku=C11CC36201*WF-2540
gies is emerging that can better the negatives of stan (incorporated by reference herein ).
dard immunoassays (e.g.with shorter time, or clinic- 65 D.Additional Discussion of State of the Art
free on field tests). We believe our invention can The three general present state of the art categories of
provide benefits in this area. manipulating liquid droplets are as follows:
35
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US 10,525,472 B1
19 20
First Category: Original Assignee Purdue Research Foundation
One class of devices to move liquid droplets is the work Third Category:
byKarlBohringer.Below arehis references. The first link The final andmost popular device uses the principle of
shows a video on public site. In their devices,microscale electrowetting (and the technology thereby iscalled digital
textured surfaces (e.g. tracks and pillars)are patterned and 5 microfluidics) to move droplets. The idea uses electrical
fabricated in silicon or glass substrates. The surface and voltages through planar electrodes to change the contact
tracks are vibrated by orthogonalwaves at a frequency and angle ofliquid droplets.When the contactangle is lower,the
amplitudethatissufficienttomove the droplets.Dropletsof dropletwets the surface;whilea highercontactanglemakes
volumes around 10 microliters canbemoved in pre-defined the dropletmore spherical for transport. The original idea
manner using the vibration ofpatterned and textured sur- 10 was conceivedby C.J.Kim from UCLA who later sold his
faces (called " ratchets”). In their patent, they claim that company to Advanced Liquid Logic.
means of generating the vibration is notimportant,and can http://www.mae.ucla.edu/news/news-archive/2012/pro
be through a piezo actuator or an audio speaker. The
vibrations change the contact angle of droplets, which also fessor-cj-kims-start-up-experience-excerpt-from -the-ucla
dependson the amountofareatextured .Vibration frequency 15 invents-magazine (incorporatedby reference herein ).Aaron
is 1Hz through 100 Hz. Their method has been highlighted Wheeler's group atUniversity of Toronto has been pursuing
in science tech newsforpotentialuse in portable diagnostics digitalmicrofluidics technology based on the above elec
(e.g.first link below ).http://scitechdaily.com/portable-diag trowettingprinciples.Hisresearch website discusses a num
nostics-use-vibration-to-move-drops-of-liquid/ ber of applications of digitalmicrofluidics for cellculture
1) Todd A.Duncombe, E.Yegan Erdem , Ashutosh Shastry), 20 and molecular diagnostics.
Rajashree Baskaran and KarlF. Bohringer,"Controlling http://microfluidics.utoronto.ca/research.php (incorpo
Liquid Drops with Texture Ratchets”, Advanced Materi rated by reference herein ) His “Publications List” has dis
als, Volume 24, Issue 12,pages 1545-1550,Mar.22, 2012 cussed the potential applications. His recent publications
(incorporated by reference herein ). include:
2) Duncombe T A, Parsons J F, Bohringer K F, “Directed 25 1) Analysis on the Go: Quantitation of Drugs ofAbuse in
drop transport rectified from orthogonal vibrations via a Dried Urinewith DigitalMicrofluidics and Miniature Mass
flat wetting barrier ratchet.” Langmuir. 2012 Sep. 25; Spectrometry
28(38):13765-70 . Epub 2012 Sep. 10 (incorporated by 2) Automated DigitalMicrofluidic Platform forMagnetic
reference herein). Particle-Based Immunoassayswith Optimization by Design
3) Vibration-driven droplet transport devices having tex- 30 of Experiments
tured surfaces: U.S.Pat.No. 2,009,021 1645 A1 Appli Sandia National Labshas an ongoing program on digital
cation number U.S. Ser.No.12/179,397; Publication date microfluidics atLivermore, Calif.ledby Dr.Anup Patel. The
Aug. 27, 2009 Inventors: Karl F. Bohringer, Ashutosh group has recently received a 5 million IARPA funding
Shastry (incorporated by reference herein ). (alongwith someUniversity partners) from a division called
Second Category: 35 Bio-Intelligence Chips (BIC ). 2012 R & D I 00 Winner:
Another class of devices for moving liquid droplets is http://www.rdmag.com/award-winners/2012/08/modular
using electrowetting and optical stimulus. The method is answer-microfluidics-transport (incorporated by reference
called optoelectrowetting. Some groups have shown its herein) https://ip.sandia.gov/technoglogy.do/techID=102
workability. The reference Light Actuation of Liquid by (incorporated by reference herein) Video: http://www.you
Optoelectrowetting is a nice review, and their projectwas 40 tube.com/watch?v=9GINROYzSJg&feature=youtu.be (in
funded by a DARPA project. In Optoelectrowetting, the corporated by referenceherein ).
platform ismade of planar electrodes through which volt A company called Advanced Liquid Logic from Duke
ages can beapplied to individual electrodes.Underneath the University uses the electrowetting technique. http://ww
electrodes is a layer of photoconductive material whose w.liquid-logic.com/ (incorporated by reference herein ).
conductivity changes when laser light is shown on it. A 45 Somevideos illustrating the idea ofusing electrical fields
combination of electrical fields (from the electrodes) and to move andmanipulate droplets is in the following videos.
light illumination controls the contact angle of droplets, Manymore videos areavailable on youtube through a search
thereby allowingto movedroplets in pre-defined directions. for “ digitalmicrofluidics” or “electrowetting”.
The group from Purdue University have a patenton opto http://vimeo.com/31391137 (incorporated by reference
electrowetting. The primarymethod is similar to the Japa- 50 herein )
nese group discussed above where virtual electrodes are http://vimeo.com/31391811 incorporated by reference
created by projected images from laser illumination. herein )
1) “Light actuation ofliquid by optoelectrowetting” http://vimeo.com/31391783 (incorporated by reference
Pei Yu Chioua,Hyejin Moonb,Hiroshi Toshiyoshic,Chang herein)
Jin Kimb,MingC.Wua Sensors and ActuatorsA 104 (2003) 55 http://www.formamedicaldevicedesign.com/case-studies/
222-228 (incorporated by referenceherein ). advanced-liquid-logic-2/(incorporated by reference herein)
Thisproject is supported in partbyDARPA Optoelectronics Patentshavebeen filed byAdvanced Liquid Logic (ALL ).
Centerthrough Center for Chipswith Heterogeniously Inte These patents are largely in two groups:
grated Photonics (CHIPS) under contract#MDA972-00-1 First group is on themethods ofusing electrical fields to
0019 60 transport,split,mix,merge,and dispense droplets. Theother
2) Open optoelectrowetting droplet actuation device and category is on the potential applications of their digital
method: U.S. Pat.No.8,753,498 B2 Priority date 25 Jun. microfluidic device to separate particles from liquids, con
2009 (incorporated by reference herein ). centrate liquid samples,orapply forexperiments in enzyme
Also published asUS20120091003 (incorporated by refer assay,pyrosequencing,and protein analysis in physiological
ence),W02010151794A1 (incorporated by reference) 65 fluids.
Inventors Han-Sheng Chuang, Aloke Kumar, Steven T. As can be seen by the several examples ofmanipulation,
Wereley size/shape of droplet pattern locations,set forth above, the

7-15
tability.16,17
US 10,525,472 B1
21 22
invention achievesits objectsofeconomical,highly flexible, The generalstrategy ofproducing and actuating discrete
automated dropletmanipulation. droplets on open surfaces relies onmethodsto modulate the
Asalso discussed above,thebenefits ofsuch a system can surface tension between the liquid droplet and the solid
beunderstoodby referencing the types of existing state of surface itrests on. The currentliterature on this topic can be
the art systems, such as electrowetting. 5 grouped into two categories— methods thatemploy electri
E.AnalyticalModel and Extension to Other Fluids cal fields to modulate the wettability of droplets3-6 and
The following is taken from Taejoon Kong, Riley Brien, nonelectricalmethods that employ mechanical, magnetic,
Zach Njus,UpenderKalwa and Santosh Pandey,Motorized acoustic orgravitationalforces to generate directionalmove
actuation system to perform droplet operations on printed ment of droplets.
plastic sheets. Lab Chip, 2016, Advance Article, DOI: 10 The electricalor ‘electrowetting-on-dielectric'method of
10.1039/C6LC00176A, Published on 8 Apr. 2016. (incor droplet actuation has gained popularity in the last decade
porated by reference herein ). primarily because of the ease ofprogrammability and por
This adds an analyticalmodeland discussesmore tests to Here, the conductive liquid droplet sits on
show the feasibility ofthe instrument in testingother fluids. patterned electrodes coated with a hydrophobic dielectric
Electronic supplementary information (ESI) available: 15 layer. An electric field applied to the target electrode
Supplementary figures and videos of droplet manipulation increases the contact angle ofthe dropletplaced over it,and
included. See DOI: 10.1039/c61000176a. thus alters the wettability of the liquid surface to the solid
Wedeveloped an open microfluidic system to dispense surface.This electrowetting phenomenon can be scaled up to
and manipulate discrete droplets on planar plastic sheets. move and controlmultiple droplets over an array of elec
Here,a superhydrophobic materialis spray-coated on com- 20 trodes, thereby performing any desired sequence of opera
mercially-available plasticsheets followed by the printingof tions including transport,merging,mixing, splitting, and
hydrophilic symbols using an inkjet printer. The patterned dispensing. Analogous to digital microelectronics where
plastic sheets are taped to a two-axis tilting platform ,pow pockets ofelectrons are transferred between devices (e.g. in
ered by steppermotors, that providesmechanicalagitation charged coupled devices), several groups have realized
for droplet transport.We demonstrate the followingdroplet 25 electrowetting-based digitalmicrofluidic platforms'having
operations: transport ofdroplets of different sizes, parallel electrodes ofprecisely-controlled geometry,on-chip control
transportofmultipledroplets,merging andmixing ofmul electronics to energize individual electrodes, and software
tiple droplets, dispensing of smaller droplets from a large programsto automate the droplet operations.3,18,19
droplet or a fluid reservoir, and one-directionaltransport of Even though the electrowetting method is widely
droplets. As a proof-of concept, a colorimetric assay is 30 accepted asthe gold standard for droplethandling systems,
implemented to measure the glucose concentration in sheep it is restrained by theneed forhigh electricalvoltages(in the
serum . Compared to silicon-based digital microfluidic range of 100 volts to 400 volts) that have unknown effects
devices, we believe that the presented system is appealing on the biomolecules or cells within droplets. For
for various biological experiments because of the ease of instance, the electric actuation force can interfere with the
altering design layouts of hydrophilic symbols, relatively 35 adsorption of biomolecules on a surface.21 Furthermore,
faster turnaround timein printing plastic sheets,larger area droplet actuation is dependent on the conductivity of the
to accommodate more tests, and lower operational costs by droplet and the dielectric properties of the insulating layers
using off-the-shelfproducts. (e.g. Teflon and Parylene) thatare expensive for large-scale
deposition. Because each electrode is electrically addressed,
INTRODUCTION 40 there are only a finite number of electrodes that can be
addressed on a digital microfluidics platform .
Generally speaking, microfluidic platforms consist of around this last issue, it has been shown thatthe electrodes
closed channelnetworkswhereliquid flow is controlled by can be optically stimulated (and thereby producing on
mechanical,pneumatic or electrokinetic means. Today,with demand optical interconnects) by incorporating photocon
emphasis on higher experimental throughput, microfluidic 45 ductive and high dielectric constantlayers underneath the
platforms incorporate several on-chip components (e.g. Teflon coating. Activematrix arraysofthin film transis
microvalves micropumps, and microelectrodes) that tor (TFTs) have also been demonstrated as an alternate
increase the complexity in fabricating the differentlayers, digitalmicrofluidic testbed wheremany thousand individu
integrating themicro and macroscale components, and con ally addressable electrodes could sense, monitor, and
trolling the individual sensingor actuation parts. In con- 50 manipulate droplets.22 Similarly, electrodes can be selec
trastto closed-channelmicrofluidics,open microfluidic plat tively energized to reposition water volumes in an otherwise
formsobviate theuse ofpolymeric channels and continuous liquid paraffin medium to create reconfigurable, continuous
liquid flow ; therebyrelaxing the fabrication process,easing flow microfluidicchannels.24 Astheseinnovationsin digital
the system integration to fewer components, and promising microfluidics technology extendthe functionalities to newer
a cheaper alternative to robotic micro-handling systems. 55 arenas of portable diagnostics, much of the fabrication
In openmicrofluidics, liquid is dispensed from a reservoiras protocol still requires access ofindustrial-grade microelec
discretized droplets and transported to desired locations for tronics foundry and is thus limited to selectusers.
furthermanipulation. Typical operations to be performed To eliminate some of the limitations of electrowetting
with discrete droplets may include transport of a single or mentioned above, non-electricalmethods of droplet actua
multiple droplets, merging and mixing of two droplets, 60 tion have been pursued.9,11-15 In the textured ratchet
incubation and affinity bindingwithin droplets, extraction of method,movementofliquid droplets is achieved on textured
solid particles from the liquid phase,and removal ofwaste microstructures i.e. ratchets) fabricated in silicon or elas
droplets.»,5 These droplet operations are often conceptual tomeric substrates.15 The textured ratchets are placed on a
ized from test tube experiments performed in a wet chem level stagethatis vertically vibrated using a linearmotor.At
istry laboratory, and the sequenceofoperations can be easily 65 the resonant frequency of vertical oscillations, the liquid
altered depending on the actual experiment being per droplet is ableto advanceorrecedeon the textured ratchets.
formed . The movement of different droplets can be individually
18-20
22
To get
8.23
1,2
3,4

tricity).21
27
US 10,525,472 B1
23 24
controlled,both in linearand closed tracks,bymanipulating droplets on hydrophilic symbols printed on a superhydro
the volumeand viscosity ofdroplets. In the superhydropho phobic surface. FIG . 23a showsthe system configuration,
bic tracks'method, shallow grooves are cut in zincplates or including the three structural components: base, vertical
silicon substrates.14 This is followed by a superhydrophobic column, and upper stage. The dimensions of these compo
coating step by depositing silver and fluorinated thiolsur 5 nents are as follows: base (20 cmx20 cmx0.5 cm ); vertical
factant on metal plates or a fluoropolymer on silicon sub column (1 cmx1 cmx10 cm ); upper stage (9 cmx9 cmx1.3
strates. The produced superhydrophobic tracks are able to cm ). The entire three-dimensional structure is designed in
confine liquid droplets and guide their movementin trajec AutoCAD (AutodeskTM ) and the separate components are
tories defined by thetracks.In the “surface acoustic waves machined in acrylic glass (PlexiglasTM ). The stage is con
(SAW )’ method, a high frequency source connected to 10 nected to the column by a universal joint that enables
interdigitated gold electrodes generates acoustic wavesthat two-axis rotation about a central pivot. Two steppermotors
is able to transport fluid droplets on a piezoelectric sub (NEMA-17TM , 200 stepsper revolution, 12 volts, 350 mil
strate.25 Recently,pneumaticsuction through a PDMSmem liamperes, bipolar mode) are connected with individual
brane has been used to activate and move droplets in two timing belts to the stage and mounted to the base. Each
dimensions on a superhydrophobic surface without any 15 stepper motor controls one axis of rotation of the stage
interference from an external energy (e.g.heat,light, elec through an Arduinomicrocontroller (Adafruit IndustriesTM ).
Single commands to tilt the stage up or down, left or right,
While the above non -electricalmethods demonstrate that and any sequence of such commands are programmed in a
mechanical machining the substrate can passively move computer workstation and transmitted through a universal
droplets, more results are needed to match the level of 20 serialbus (USB ) connectionto the Arduinomicrocontroller.
droplethandling operationsachieved in digitalmicrofluidic A graphical user interface (GUI) is designed for remote
platforms. To gaugethematurityofdigitalmicrofluidics,an access to the droplet actuation system using a standard
exciting example is a multi-functional digitalmicrofluidic computerworkstation (see ESI†FIG .33).For image record
cartridgeby Advanced Liquid Logic that can perform mul ing and characterization of droplet operations, a webcam
tiplexed real-time PCR, immunoassays and sample prepa- 25 (Logitech C920TM ) ispositioned above the stage to monitor
ration.20 A group at Sandia NationalLaboratories hasdevel and record the simultaneousmovementofmultiple droplets.
oped a digital microfluidic distribution hub for next Preparation of Plastic Sheets
generation sequencing that is capable of executing sample Afterassembling thestructural components ofthedroplet
preparation protocols and quantitative capillary electropho actuation system , we prepare the surface of plastic sheets
resis for size-based quality control of the DNA library. 30 thatwill serve as an open microfluidic arena to hold and
With growing demand oflab on chip systemsin medicine, move discrete droplets (FIG . 23b). Initially, letter-sized
digital microfluidics has been used to extract DNA from transparency films (Staples Inc.TM) are rinsed with distilled
whole blood samples,28 quantify the levels of steroid hor waterand spray-coatedwith a commercially available supe
mones from breast tissue homogenates, and screen for rhydrophobic coating (Rust-Oleum NeverWetTM ). The coat
metabolic disorders and lysosomal storage diseases from 35 ing procedure is a two-step process that involvesdepositing
newborn dried blood spots.30-34 These examples highlight a base coatand a top coatprovidedby the supplier. Thebase
the fact that digitalmicrofluidics is revolutionizing the field coatis applied bysprayingon the surface ofthetransparency
ofportable medical diagnostics, and any rival technology film . Three applicationsof the base coat are performed with
needs to achieve thebasic standards of droplethandling set awaittimeoftwominutes between successive applications.
by digitalmicrofluidics. 40 After drying for one hour, four applications ofthe top coat
In an attemptto emulatethe dropletoperationsperformed are performed in a similar fashion. The superhydrophobi
in digital microfluidics without the use of high electrical cally -coated plastic sheet is dried for 12 hours at room
voltages or micromachining steps, we present a system temperature. Thereafter,hydrophilic symbols are printed on
where droplets are manipulated on a superhydrophobic the plastic sheetby inkjet printing.For this step, the plastic
surface (created on plastic sheets) by gravitational forces 45 sheet is loaded into the document feeder ofa commercial
and mechanical agitation. The superhydrophobic plastic ink-jet printer (Epson WF-2540TM ). The layout of the
sheets are further printed with unique symbols using a desired symbolsare drawn in Adobe Illustrator,saved on the
hydrophilic ink.A microcontroller controls the direction and computer, and printed using a black ink cartridge (Epson
timing of two stepper motors which , in turn, provide T200120TM ).After printing, theplastic sheet is dried for 12
mechanical agitation for droplet transport.Dropletsremain 50 hours at room temperature. Using theabove procedure, a
confined to thehydrophilic symbols, andare able to ‘hop'to single letter-sized transparency film can produce six printed
neighbouring symbols by gravity when the surface is agi templates (9 cmx9 cm ) in one run.
tated andtilted to a certain degree.Using thisbasic principle, Remote Control and GUI Software
we illustrate the following droplet operations: transport of A graphicaluser interface (GUI) software is developed in
single and multiple droplets, transport of larger-volume 55 Matlab to remotely access and controlthemechanicalmove
droplets,merging andmixing ofmultiple droplets, dispens ment of the droplet actuation system . The Adafruit Motor
ing of fixed-volume droplets from a large droplet or liquid Shield vl communicates with the Arduino microcontroller
reservoir, and one directionalmovementofdroplets. As a through the 12C (InterIC ) protocol and controls each of the
proof-of-concept,we show the application ofthesystem as steppermotors. The Arduino is further controlled from a
a colorimetric assaytodetecttheconcentration ofglucosein 60 computer workstation using the Arduino Integrated Devel
sheep serum . opment EnvironmentTM. TheGUI enables commands to be
easilysentto the Arduinomicrocontroller. Thescriptaccepts
EXPERIMENTAL inputs to set the speed and number of steps taken by the
motors,which ,in turn, controlstheangularmovementofthe
Design of the Droplet Actuation System 65 stage about thecentralpivot. TheGUIhas options to control
The motorized actuation system consists of a two-axis motor parameters, such as the number of steps, speed of
tilting platform to manipulate movement of discrete liquid rotation,and direction ofrotation which eventually control
29

35
US 10,525,472 B1
25 26
the angular movementofthe stage aboutthe centralpivot. error ismeasured in each case.Negative displacementerror
In the default state, the position of the stage is assumed occurs when a droplet fails to detach from theinitial symbol.
horizontal and is calibrated using a bubble level (Camco Conversely, positive displacement error occurs when the
Manufacturing Inc.TM).When the GUIsoftware is first run, droplettravels beyond the neighbouring symbol (see ESIT
theconnection to the Arduino microcontroller is established 5 FIG . 34c).In all cases, thedroplet volumeis 10 ul,tilting
automatically by searching active COM ports. Once the speed is 100 r.p.m., and number of steps is 14. Theresults
Arduino COM port is confirmed to be connected, the user indicate that symbols with thicker line widths produce
can enter the sequence of mechanical operations to be negativedisplacement error as theyhave more surface area
performed. In theGUIwindow,pressing the double arrows to hold the droplet in its original position (see ESI† FIG .
increases the stage's angle ofrotation in the corresponding 10 34b).On the other hand, symbolswith thinner line widths
direction (see ESIT FIG . 33). The single arrow button produce positive displacementerror as theyhaveinsufficient
rapidly tilts the stage to a specified angle, and then returns surface areato hold orcapture a sliding droplet. Theoptimal
it to the default horizontalposition. In addition, the GUI linewidth is 0.02 cm and theinter-symbolspacing is0.335
software communicates with a webcam to display a live cm ,which produces anegligibledisplacementerrorof0.005
preview of the top surface and record images or videos of 15 cm .Wealso found that,using this optimaldimension ofthe
droplet actuation. plus symbol, we can transport single droplets having a
Chemicals minimum and maximum watervolumeof 8 uL and 38 uL,
Glucose assay kit (Sigma-Aldrich, GAGO20) is com respectively.
posed of the following chemicals: glucose oxidase/peroxi PhysicalModel forDropletDetachmentfrom a Hydrophilic
dase (Sigma-Aldrich, G3660), and o-dianisidine reagent 20 Symbol
(Sigma-Aldrich,D2679).Glucose standard (Sigma-Aldrich, Following the force balance analysis of Extrand and
G6918 ) and sheep serum (Sigma-Aldrich, 53772) are also Gent, weassumethe contactregion of a liquid droplet on
used. The glucose oxidase/peroxidase reagent is dissolved in thesuperhydrophobic surface is circularwith a radiusR.The
39.2 mlof deionized water.Next, o-dianisidine reagent is droplet is about to detach from thehydrophilic symbol and
added in 1 mL of deionized water. The assay reagent is 25 travel downwards as the stage is tilted from its horizontal
prepared by adding 0.8 mL ofthe o-dianisidine solution to position to a critical angle a (see ESI† FIG . 35a). If the
the 39.2 mL of the glucoseoxidase/peroxidase solution and angular speed of the stage is w revolutions per minute
mixing the solution thoroughly. The glucose standard solu (r.p.m.) and the time for rotation is At minutes, then the
tion is diluted to create 0.7mgmL-1, 0.6 mgmL-',0.5mg criticalangle a=21•w•Atradians. The parameter At can be
mL-1,0.4 mgmL-1,0.3mgmL-1, 0.2mgmL-1, and 0.1mg 30 further expressed as At=N.t,minuteswhere N is thenumber
mL-1 standardsin deionized water.Forcontrolexperiments, ofstepsof themotor and t is the timeforone step rotation.
deionized water and black food dye(ACH FoodCompanies The 'advancing edge' and 'receding edge' are labelled (see
Inc.) are used. ESI† FIG . 35b). For the plus symbol, the hydrophilic line
Result and Discussion width is w and the length is 2xR . The liquid droplet has a
Transport of a Single Droplet 35 surface tension y, contact angle 0, viscosity n, density p,
FIG . 24a showsthe side-view of a single droplet placed volume V, radius r (such that V= (4/3).T:r ), and linear
on a hydrophilic symbol (left side) printed on a superhy velocity v (such that v=w's,where =3 cm is the distance
drophobic layer.Asthe stage is tilted clockwise, the droplet from the pivotto the centerof stage). The azimuthal angle
remains on the hydrophilic symbol. But, as the stage is º circumnavigates the perimeter of the contact region
quickly tilted anti-clockwise to the default horizontal posi- 40 between a value of0-0 at the rear end ofthe droplet to a
tion, the dropletslides down the superhydrophobic surface value to p=r/2 attheadvancingside ofthedroplet.There are
and rests on the neighbouring hydrophilic symbol (right three forces acting on the droplet as the stage is tilted:
side). In FIG . 24b, side-view images of a single droplet are surface tension F gravitation force FG,and viscous force
shown as it slides from the leftsymbolto the rightone.The Fy.Atthe criticalangle a ofthe stage, the individual forces
time for transporting a single 10 ul dropletbetween two 45 balance as:
consecutive symbols is approximately 100 milliseconds.
The stage is tilted at 100 revolutionsperminute (r.p.m.)and Fst+ F -FG
the number of steps is 14. In eqn (1), the surface tension force Fst can be divided
The basic principle of droplet transport thus relies on into two components: force F, acting on the rear of the
positioning a dropleton a hydrophilicsymboland providing 50 droplet and force F, acting on the advancing front ofthe
a rapid tilting action (i.e. tilting the stage clockwise (or droplet. Plugging in the expressions for the gravitational
anticlockwise) to a specific angle followed by tilting the force FG acting parallelto the stage andthe viscousforceFy,
stage anti-clockwise (or clockwise) to the horizontal posi we get:
tion). Therapid tilting action allows us to use small tilting (F,-F2)+6'A'n?r.v =p.V.g-sin a (2)
angles (3-5°) with accelerationanddeceleration ofa droplet. 55
Alternatively, a single droplet can be transported by slowly To compute the surfacetension force, its component fper
tilting the stage in onedirection which,however, requires a unit length ofthe contact perimeter varies along the perim
larger tilting angle (9-20°) and provides no control on eter as:3
stopping the accelerated droplet. (3)
We found that droplet transport can be controlled by a 60 fy.cos 0.cos o
series of hydrophilic symbols printed at regular intervals. To simplify the calculation,we assume that cos o varies
Based on initial tests,we chose to use 'plus(+)'symbols to linearly around the perimeter ofthe contactregion between
demonstrate single droplet transport.Other symmetric sym a receding value of cos O, at the rear end of the droplet
bols can also be used for this purpose. We printed plus (whereo =0)to an advancingvalueofcos0,attheadvancing
symbols of different line widths and inter-symbolspacings 65 sideofthe droplet (where p = /2). For the case ofa droplet
(see ESIF FIG . 34a). The transportofsingle droplets on the on a homogeneous superhydrophobic surface, the expres
different symbols is recorded, and an average displacement sion for the contact angle is given by:35
ST
35

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