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Algorithm for a microfluidic assembly line Tobias M. Schneider, Shreyas Mandre, and Michael P. Brenner School of Engineering and Applied Sciences, Harvard University, 29 Oxford Street, Cambridge, MA 02138 Microfluidic technology has revolutionized the control of flows at small scales giving rise to new possibilities for assembling complex structures on the microscale. We analyze different possible al- gorithmsforassemblingarbitrarystructures,anddemonstratethatasequentialassemblyalgorithm can manufacture arbitrary 3D structures from identical constituents. We illustrate the algorithm byshowingthatamodifiedHele-Shawcellwith7controlledflowratescanbedesignedtoconstruct the entire English alphabet from particles that irreversibly stick to each other. 1 Developing novel methods for assembling complex (a) inlets with 1 structures from small particles has been the focus of controlled flowrates 0 much recent investigation [1, 2]. Traditional approaches 2 have mostly revolved around designing selective interac- n tions between constituent elements of the assembly. The a structureisthenassembledintheabsenceofanyexternal J controlifthermalfluctuationscandrivethesystemtoits 9 free particles energetic ground state [1, 3], although non-trivial energy 1 landscapes often render this approach challenging. ] Hereweconsideradifferentpossibilityforassemblyon (b) (c) n small scales, in which microfluidic flow control is used to y steerand assemble smallparticlesintostructuresof high d - complexity. The basic idea follows from the observation u that if we could construct an arbitrary time dependent l f flow field (cid:126)v((cid:126)x,t), then particles in the flow could be ad- . s vectedalongarbitrarypathsandmovedtoarbitraryloca- c tionsatafixedtime. Thisapparentlyallowstoconstruct i s any complex structure, with the individual components y binding irreversibly upon contact. 30 1 h p Of course, the flow field(cid:126)v((cid:126)x,t) cannot be arbitrary; it 20 0.5 [ must conserve mass and momentum [4], 1− 10 1− v1 ∇·(cid:126)v =0, −∇p+µ∇2(cid:126)v+ρ(cid:126)b=0. (1) /fπaHδτk-100 /fπaHδτk-0.05 1 -20 9 where p is the pressure, µ the liquid viscosity and(cid:126)b is a -30 -1 0 0.2 0.4 0.6 0.8 1 0 0.2 0.4 0.6 0.8 1 7 volumetricforce. Thequestionofwhatstructurescanbe t/τ t/τ 3 builtthushingesonwhatflowfieldscanbeproducedus- FIG. 1: (Color online) (a) Schematic: Five particles are ad- . vected by the flow field in a circular cell. The flow field, 1 ingcurrenttechnology[5],andwhatarethelimitsforthe visualizedbyitsstreamlines,issetupbyelevenflowratesim- 0 possible structures that can form with such flow fields. posed on the boundary (arrows indicating the strength and 1 Volumetric forces can be produced using e.g. magnetic direction). (b/c)Twotrajectoriestransportingparticlesfrom 1 fields [6] or optical tweezers [7]; alternatively, the flow afixedinitialtotheirdesiredfinalpositionwiththerequired : v can be generated by inlets specifying (cid:126)v at the boundary flowrates. The linear trajectory (b) requires flowrates almost Xi of a cell. 2ordersofmagnitudehigherthanthetrajectoryin(c). This optimized trajectory minimizes dissipation. Flowrates are We analyze the case where pressure inlets around the ar boundary force the flow (Fig. 1), and (cid:126)b = 0. Fluid giveninunitsoftheraterequiredtotransportasingleparticle in one time unit across the cell. mechanical constraints prohibit simultaneous control of manyparticleswiththisdevice;however,wedemonstrate that a sequential assembly algorithm allows the assem- bly of arbitrary structures. The device can be designed scribed velocity (cid:126)v((cid:126)x,t), (cid:126)x ∈ ∂Ω. The linearity of (1) to manufacture the entire English alphabet using 7 con- implies the velocity of the suspended particles is linear trolled flow rates in two dimensions. in the boundary forcing [4], i.e. Linear Response to Boundary Forcing. Consider N particles suspended in the flow domain Ω with their in- N (cid:90) stantaneous positions being (cid:126)xj, j = 1,2,...,N. Let the (cid:88)Rjk(cid:126)x˙k = Kj((cid:126)x1,x(cid:126)2,...x(cid:126)N;ξ(cid:126))(cid:126)v(ξ(cid:126),t) dS+F(cid:126)j,(2) flow be forced on the boundary of the flow cell by a pre- k=1 ∂Ω 2 where F(cid:126) is the force acting on the jth particle, possibly in the far field. j duetonon-hydrodynamicinterparticleinteractions. The WeconsiderthedevicedepictedinFig. 1(a),acircular responsecoefficientsK andR dependonthegeometry domain of radius a with flowrates f prescribed at the j jk k of the flow cell [8] and can be computed numerically. If, boundary at M discrete inlets with positions R(cid:126) . The k the boundary forcing occurs through M discrete inlets velocity field at any position (cid:126)x is then given by of area ∆S, located at ξ(cid:126) with prescribed velocities (cid:126)v , k = 1,2,...,M, then Ekqn. (2) can be written in thke (cid:126)u((cid:126)x)=− 1 (cid:88)M (cid:126)x−R(cid:126)k f ≡B((cid:126)x)·f. (4) discrete form πH ((cid:126)x−R(cid:126) )2 k k=1 k R(x) x˙ =M(x)·f +F, (3) Thus, the matrix M in Eqn. (3) may be constructed by combining the N position dependent matrices B(x(cid:126)) i with x = [(cid:126)x1,(cid:126)x2,...,(cid:126)xN], flowrates f = corresponding to each particle. [(cid:126)v ,(cid:126)v ,...,(cid:126)v ]∆S and M =K ((cid:126)x ,x(cid:126) ,...x(cid:126) ;ξ(cid:126) ). We first test whether this flow cell will allow simulta- 1 2 M jk j 1 2 N k neous control of all N particles by boundary inlets. The Eqn. (3) is an instantaneous linear relation between flow rates scale inversely with the duration of the assem- the imposed flowrates and the particle velocities. This bly so that the scale for the flux depends on the chosen implies that prescribed particle trajectories x(t), may be timescale. Wescaleflowratebythefluxrequiredtomove realizedbyimposingsuitablef obtainedbyinverting(3). a single particle across the cell F = πaHδ/τ, where δ is Thefeasibilityofthismethodthenhingescruciallyupon the width of the inlet and the duration τ of the pro- invertibility of M, which in general needs not be square. cess. Fig. 1(b) shows that if we require the particles to Condition for Controlling Particle Trajectories. A betransportedinstraightlinesatconstantvelocityfrom necessary condition for inverting M is that the number their initial position to their final position, the required of independent controls exceed the number of degrees of flowrates reach up to 30 times this value. This happens freedom. With N particles in 3 dimensions, there must because when two or more particles are moving towards be at least M = 3N +1 flow inlets; 3N inlets control each other a distance (cid:15) apart, a strain rate field of (cid:15)˙/(cid:15) is particle degrees of freedom, with the additional inlet en- required. If the approach velocity is constant, the strain forcingvolumeconservation. Similarlyintwodimensions diverges as (cid:15) → 0, implying diverging flowrates. Thus, at least 2N +1 flow inlets are required. whenever particles are brought together at constant ve- Ingeneral, thesealgebraicconditionsarenotsufficient locity, large fluxes are required. for the practicality of this assembly method. We will see OptimizedTrajectories. Wecantrytoreducetheflow belowthatinpractice,theflowratesrequiredtoindepen- ratesbychoosingtheparticletrajectoriesandspeedscon- dentlysteerlargenumberofparticlescanbetoolargeto necting the initial and the final states to minimize this bepractical,owingtothepoorconditioningofthematrix effect. Intuitively, we can decrease the speed of the par- M. ticles as they approach each other to minimize the re- Hele-Shaw Flow as a Specific Example. To explore quired flowrates. To find out if this is sufficient we com- this in more detail, we consider a specific example. We putetheoptimaltrajectoriesconnectingtheinitialtothe consider the fluid mechanics of typical microfluidic de- desired particle configuration by finding the trajectories vices [9] where the vertical gap thickness H is much that minimize dissipation. The dissipation rate is given smallerthanthelateralextent. InHele-Shawapproxima- by tion [8], the velocity profile across the gap is a parabola, with the gap-averaged velocity (cid:126)u being proportional to H2 (cid:90) w = |∇p|2dA. (5) the gradient of the pressure field p satisfying Laplace’s 12µ A equation. A particle at position (cid:126)x responds to the flow k by moving at a speed proportional to the local fluid ve- For the discretized forcing w can be expressed as a locity, (cid:126)x˙ = β(cid:126)u((cid:126)x ), with β depending on the particle quadraticformintheflowratesw =f†·D·f withmetric k k sizeandshape[8]. Thislineardependenceoftheparticle D beinganalyticallygivenintermsoftheinletpositions. velocity on the gap-averaged fluid velocity is a general We minimize the dissipation and thereby the flowrates consequence of the linearity of Stokes flow. The quanti- under the constraints that the dynamics move the parti- tativevalueforβcanbecalculatedintwodifferentlimits: cles according to their equation of motion Eqn. (3) from Iftheparticleismuchsmallerthanthegap,itisadvected their chosen initial state to their final state. This re- by the local velocity, so β depends on the location of the quires that we find the trajectories that minimize the particle relative to the walls. Alternatively, if the par- Lagrangian toifclsecaalpepurnodxiemrlaytinelgytshpeaHnselteh-Sehgaawpawpipdrtohx,itmhaetsioenpabrraetaiokns L=(cid:90) 1dt(cid:110)f†·D·f −λ†·(cid:2)x˙ −M ·f(cid:3)−γ e†·f(cid:111) (6) down near the particle. The factor β can now be calcu- 0 latedbysolvingtheStokesequationsclosetotheparticle, where λ and γ are Lagrange multipliers to enforce the matchingthesolutionwiththeparabolicHele-Shawflow constraints and e† = (1,...,1). λ enforces the equation 3 of motion, whereas γ requires that the fluxes f satisfy particle positions in the aggregate’s frame of reference volume conservation. and R is the two-dimensional rotation. How many de- TominimizeLweconsiderasmallperturbationofthe grees of freedom are required for the assembly? Control- flowrates in the direction of steepest descent, i.e. f → ling the position of the aggregate requires two degrees f +∆f with of freedom. Rotating it requires a stagnation point flow superimposedonthelocalmeanflowneartheaggregate. (cid:18)δL(cid:19)† (cid:110) (cid:111) Thisrequiresindependentcontroloftwomoredegreesof ∆f =−(cid:15) =−(cid:15) 2D·f +M†·λ−γe . (7) δf freedom, the strength and orientation of the stagnation point flow. Finally, the free particle location demands To fix the unknown fields γ and λ we require the vari- twoadditionaldegreesoffreedom. Includingvolumecon- ation of L with respect to x,λ and γ to vanish for the servation we thus need 7 inlets to absolutely control all updated flowrates and trajectory x → x + ∆x. Eval- degrees of freedom. uating the stationarity condition at linear order in the Sequentially adding particles allows to assemble struc- increments allows to eliminate γ from Eqn. (7) and se- tures of arbitrary shape and thus spell a word (Fig. 2) lects a unique solution of the adjoint equations withoutanyfeedbackcontrol. Technically,thetrajectory ∂M for a particle to be added is constructed by defining the λ˙ =−f mnλ (8) k n ∂x m desiredpositionwhichistakenfrom[10]andthedirection k of approach in the frame of reference of the aggregate. whicharenumericallysolvedtogetherwiththeevolution Spline interpolation between the initial position of the of x using MATLAB. [13] newparticleanditsfinalpositionwhentheaggregatehas The minimization starts from the linear trajectory in reachedthedesiredconfiguration,thenyieldstheparticle Fig.1(b)alongwhichwechoosevelocityvariationsdamp- path. The aggregate can also be moved arbitrarily; we ing large peak flowrates. Panel (c) shows the same 5 choose to keep its orientation fixed and move the center particles following an optimized trajectory for which the of mass to the device center in each step. The velocity flowrates are reduced by more than an order of magni- alongthistrajectoryischosensuchthatitvanishesatthe tude,tothedesiredrange. Thereductionisduetochoos- ing (cid:15)˙/(cid:15) to approach a finite number as (cid:15)→0. Thus, op- timizing trajectories can lead to simultaneous control of a modest number of particles using boundary flowrates. Nonetheless, this approach does not scale to larger number of particles; e.g, we could not find trajectories allowing simultaneous control of 13 particles required to spell the letter ‘B’ at moderate fluxes. This reflects a implementation independent physical limit of directing flow fields with boundary fluxes, resulting from the fact that flow modes forced at the boundary decay in ampli- tude as one moves away from the wall. The character- istic length scale governing the decay of the boundary modesisthedistancebetweentheinjectionpointswhich scales inversely with the number of inlets. But as the particlenumberincreases,weneedmoreinletstocontrol the particle motion. This limits the number of particles that can be controlled simultaneously. In our numerical experiments we could not find trajectories transporting more than 6 individual particles at moderate flowrates. Sequential Assembly. To overcome this physical limi- tation, an algorithm is required that decouples the num- ber of controlled degrees of freedom from the num- ber of particles in the desired structure. This can be achieved with a sequential approach, where one parti- cle after the other is attached to an aggregate which moves as a rigid body subject to force- and torque bal- FIG. 2: (Color online) Sequentially particles are added to form aggregates of arbitrary shape. The three columns ance. Construction of the corresponding M matrix re- presentsnapshotsalongtheassemblyofthreeexamplestruc- quires explicitly accounting for the translation and rota- tures presented in the last row. The required time-variation tion of the cluster consisting of Z particles at positions of the seven controlled flowrates are computed a priori (eg. (cid:16) (cid:17) (cid:126)x =(cid:126)x +R(ϕ) ξ(cid:126) −ξ(cid:126) whereξ(cid:126) aretheprescribed Fig. 3). See movie M1 (online) for an animation. α cm α cm α 4 1 0 plement feedback control [12], though this significantly -1 1 complicates the process especially for three dimensional 0 -1 structures. Another intriguing possibility is to simply 10 embrace the existence of stochasticity and construct the -1 most stable trajectories that maximize the probability 1 0 -1 of formation of the desired structures in the presence of 10 noise. Finding algorithmic methods for carrying out this -1 optimizationareimportantdirectionsforfutureresearch. 1 0 -1 1 0 We acknowledge support by the National Science -1 0 1 2 3 4 5 6 7 8 9 10 11 12 13 Foundation; the Kavli Institute for Bionano Science and t FIG. 3: (Color online) Flowrates fk/πaHδτ−1 for the seven Technology at Harvard; and the German Science Foun- inletsasafunctionoftimet/τ. Theseallowtospelltheletter dation through grant Schn 1167/1 (TMS). ‘B’. At each integer time a new particles enters the cell. initialandfinalconfigurationsothatflowratesreachzero aftereachassemblystep. Withthischoiceoftrajectories, [1] G. Whitesides and B. Grzybowski, Science 295, 2418 the flowrates are computed inverting Eqn. (3). No ex- (2002). tensive optimization was required to limit the fluxes (see [2] H. - Y. J. Yeh, and J. S. Smith, IEEE Photon. Fig.3)toreasonablevaluesofthesameorderasthosein Technol. Lett. 6, 706 (1994); G. Whitesides and Fig. 1(c). 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Douglas, et al., Nature 459, and the detailed assembly sequence are decided on, the 414 (2009). flowrates on the inlets of the device and the precise in- [4] J. Happel and H. Brenner, Low Reynolds number hydro- stants at which each constituent is introduced are cal- dynamics: with special applications to particulate media culated. These pre–computed flowrates are then set up (Kluwer, 1991). in a time–periodic fashion, and a train of the assembly [5] S.QuakeandA.Scherer,Science290,1536(2000);B.D. constituents are introduced at the inlets of the device to Gates, et al., Annu. Rev. Mater. Res. 34, 339 (2004); accomplish a train of assembled products. T.SquiresandS.Quake,Rev.Mod.Phys.7,977(2005); G.Whitesides,Nature442,368(2006);J.-H.Jang,etal., In summary, we have shown that microfluidic assem- Angew. Chem. Int. Ed. 46, 9027 (2007); D. Dendukuri bly can be an efficient strategy if structures are built andP.S.Doyle,Adv.Mater.21,1(2009);D.K.Hwang, sequentially. Usingthisapproach,weshowthatthetem- D.Dendukuri,andP.S.Doyle,LabChip8,1640(2008); poral control of only 7 flowrates allows to build arbi- K. Sung, et al., J. Am. Chem. Soc 130, 1335 (2008). trarily shaped particle aggregates in 2 dimensions. In [6] M.Jullien,J.Paret,andP.Tabeling,Phys.Rev.Lett.82, 3 dimensions, the same argument implies that 11 dif- 2872 (1999); N. Ouellette, P. O’ Malley, and J. Gollub, ferent flowrates are required. Different chamber geome- Phys. Rev. Lett. 101, 174504 (2008). [7] E. Dufresne and D. Grier, Rev. Scient. Inst. 69, 1974 triesandhydrodynamicinteractionscanbeincorporated (1998); D. Grier, Nature 424, 810 (2003). into this framework, which rests solely on the linearity [8] C. Pozrikidis, J. Fluid Mech. 261, 199 (1994). of Stokes flow. We anticipate that similar algorithms [9] Y. Xia and G. M. Whitesides, Annu. Rev. Mater. Sci. can be constructed using other forcing mechanisms such 28, 153 (1998); M. Hashimoto, et al., Soft Matter 4, as electrokinetics [11], where non-hydrodynamic electri- 1403 (2008). cal forcing contributions need to be included into the [10] D. M. Eigler and E. K. Schweizer, Nature 344, 524 transfer matrices. A challenge for practical implementa- (1990). [11] A. E. Cohen, Phys. Rev. Lett. 94, 118102 (2005). tion is to quantify the sensitivity of particle trajectories [12] A. E. Cohen and W. E. Moerner, Proc Natl Acad Sci to noise in the imposed flow rates. This is particularly USA 102, 4362 (2006). relevant when scaling down the assembly to submicron [13] Since the trajectory increment preserves constraints to scale, where the Pecl´et number corresponding to Brow- linear order only, we explicitly enforce in each iteration nian motion is small and hence potentially disruptive. that particles reach their prescribed final positions ex- One option for dealing with errors and noise is to im- actly. This corrects for neglected higher order effects.

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