(12) ulllted states patent (10) patent n0.: us 8,560,130 b2 ludwig...

US008560130B2

(12) Ulllted States Patent (10) Patent N0.: US 8,560,130 B2 Ludwig (45) Date of Patent: Oct. 15, 2013

(54) SOFTWARE CONTROLLED LAB-ON-A-CHIP 2007/0036024 A1* 2/2007 Kubala et al. ............ .. 366/163.2 EMULATION 2008/0223721 A1 9/2008 Cohen et al.

2009/0121476 A1 5/2009 Malito et al. >l<

(75) Inventor: Lester F. Ludwig, Redwood Shores, CA 2009/0202731 A1 8/2009 KaZkaZ et al' """""" " 427/4211

(US) OTHER PUBLICATIONS

(73) Assignee. Lester E Ludwig Belmont C A (Us) DS1920 Temperature iButton, Dallas Semiconductor Corporation ’ ’ 1997.*

* - _ - ~ ~ - Bernhard et al., “Design and Rapid Prototyping of Thin-Film Lami

( ) Nonce' SubJeCt.tO any (31531211111651 the germdof?glg nate-Based Micro?uidic Devices”, Biomedical Microdevices, Patent 15 exten e or a Juste un er Kluwer Academic Publishers, 2001.* U-S-C- 154(1)) by 622 days- Takahashi et al., “A 40-Gb/s Self-Clocked Bidirectional Serial/Par

allel Converter for Asynchronous Label Swapping”, IEEE, Mar. (21) Appl. No.: 12/328,713 2007*

(22) Filed: Dec. 4, 2008 (Continued)

. . . Primary Examiner * Carlos Ortiz Rodriguez 65 P P bl t D t

( ) nor u lea Ion a a (74) AZZ0rney,AgenZ, orFirm *Procopio, Cory, Hargreaves US 2009/0326903 A1 Dec. 31, 2009 & Savitch LLP

Related US. Application Data (57) ABSTRACT

(60) Provisional application No_ 61/005,369’ ?led on Dee A software-controlled chemical process emulation system 4 2007_ and environment having individually-addressable and/or

’ group-addressable software-controlled chemical system pro (51) In‘; C]_ cessing modules, software-controlled chemical system han

G05D 7/00 (200601) dling modules, and related components. The software-con (52) us CL trolled modules may be designed and interconnected to

USPC ........................................... .. 700/282 700/19 emulate Van'ous ?xed, Con?gurable, and recon?gurable (58) Field of Classi?cation Search “Lab-on-a-Chip” (“LoC”) devices. The software-controlled

USPC 700/275 282, 703/23 modules may be designed as separate units With Well-de?ned See ape Search ilistoliy ports and interfaces that can be used in the construction of

' larger systems. Alternatively, the software-controlled mod (56) References Cited ules may be integrated into more complex subsystems that

US. PATENT DOCUMENTS can be used in similar or other Ways. These aspects may be used to design a LoC device, develop software for the opera tion of a LoC device, or may be used together With actual LoC

2 i 1 \glillawga ~~~~~~~~~~~~~ " “81/2/1466; devices as part of a larger system. Some applications may be 5’577’890 A * 11/1996 M31282; :tnal'" """ "417/44 2 used to implement laboratory automation features in experi 636813616 B2 * 1/2004 Spaid et a1‘ 73/5467 mental set-ups and laboratory-scale chemical production. 7,002,311 B2* 2/2006 Strike et al. .... .. . 318/40013

2003/0087300 A1* 5/2003 Knapp et al. .................... .. 435/6 20 Claims, 33 Drawing Sheets

r————..—.i r ------- -: I Models Visualization ‘ : :

l l

I . . . A A‘ l Table-Scale : Actual-Scale: D n“;i|r|1(iirg§L|l/|%ge|5 I LoC Process | Physical LoC | g M d I Emulation I System I

I en_sor 0 es . Simulation l i : Reaction Models—> . |

I Physics Models—> l 'L _ _ _ _ _ _ _ H‘

l_ _ _ _ _ J A Hardware

| Driver | | Driver | | Driver |

Con?guration Control

Software @

US 8,560,130 B2 Page 2

(56) References Cited

OTHER PUBLICATIONS

Fluidic Valves for Variable-Con?guration Gas Treatment, V.Tesar, Institution of Chemical Engineers, Trans IChemE, Part A, Sep. 2005, Chemical Engineering Research and Design, 83(A9): 1111-1121, available at http://eprints.whiterose.ac.uk/758/1/tesarv6pdf. Development of a Micro?uidic Unit for Sequencing Fluid Samples for Composition Analysis, V. Tesar’k, J. R. Tippetts, Y. Y. LOWand R. W. K. Allen, Institution of Chemical Engineers, Trans IChemE, Part A, Jun. 2004, Chemical Engineering Research and Design, 82(A6): 708-718, available at http://eprints.Whiterose.ac.uld468/1/tesarv2. pdf. Sampling by Fluidics and Micro?uidics, V. Tesar, Acta Polytechnica vol. 42 No. Feb. 2002. Development of a MEMS Microvalve Array for Fluid Flow Control, Nelsimar Vandelli, Donald WrobleWski, Margo Velonis, and Thomas Bifano, Journal of Microelectromechanical Systems, vol. 7, No. 4, Dec. 1998, available at http://swsl .bu.edu/bifano/PDFi?les/23i FloW.pdf. Development of a Rapid-Response Flow-Control System Using MEMS Microvalve Arrays, John Collier, Donald WrobleWski, and Thomas Bifano, Journal of Microelectromechanical Systems, vol. 13, No. 6, Dec. 2004, available at http://128.197.153.21/tgb/PDFi ?les/Valvespdf. A Novel Pressure Balanced Micro?uidic Valve, J. M. Quero, A. Luque, L. G. Franquelo, Proc. ISCAS 2002, May 26-29, available at http://Woody.us.es/~aluque/doc/pressureibalancedimicrovalve. pdf. Fabrication of Polysilicon Micro Valve Array, Jermaine White, 22rd Annual Microelectronic Engineering Conference, May 2004, avail able at http://WWW.rit.edu/~W-ue/ameccontent/17iJWhite.pdf.

Parker R-maxTM Stream Switching System, Parker Instrumentation, Catalog 4140-R, Revised, Jun. 2002, available at http://WWWplesner. as/mod/products/upload/4140-R.pdf. Fast Switching Valves: Ultra Fast and Highly Repeatable, FESTO Corp, Info 96 207 US, Jun. 2005, available at http://WWW.Zycon.com/ Literature/219948/75280/Info207iFastSWitchingV.pdf. Flow Selection Valves: Series 105TValve, Bio-Chem Fluidics, 2010, available at https://WWW.biochem?uidics.com/cart/store/comersusi listOneCategory.asp?idCategory:393. Flow Selection Valves: Series 080TValve, Bio-Chem Fluidics, 2010, available at https://WWW.biochem?uidics.com/cart/store/comersusi listOneCategory.asp?idCategoi§P392. Cheminert® Valves for Flow Injection Analysis, FlAlab Instruments, 2010, available at http://WWW.?oWinjection.com/valves.html. Solenoid valves and eletric valve, Peter Paul Electronics Co., Inc., 2010, available at http://WWW.peterpaul.cOm/WhatsineWidisplayZ. php4?catiid:6. Gems Predyne Pneumatic Solenoid Valves & Miniature Solenoid Valves: general-purpose-valves, Gems Sensors & Controls, 2010, available at http://WWW.gemssensors.com/Search.aspX?q:general purpo se-valves. Gems Predyne Pneumatic Solenoid Valves & Miniature Solenoid Valves: isolation-valves, Gems Sensors & Controls, 2010, available at http://WWW.gemssensors.com/Search.aspX?q:isolation-valves. 1200 Series Valve Solutions, Agilent Technologies, 2000-2010, available at http://WWW.chem.agilent.com/en-us/products/instru ments/lc/ 1 200seriesvalvesolutions/pages/ default. aspX. Valve matrix takes squeeze out of juice production, Prepared Foods, Oct. 1997, available at http://?ndarticles.com/p/articles/miim3289/ isin11iv166/aii20224164? LG16, Media Isolated Micro?uidic Flow Sensor, WWW.S€I1S1I1OI1. com. Apr. 2009 , V1.1., available at http://WWW.sensirion.com/en/ pdf/productiinformation/DatasheetiLiquidiFloWiSensori LG16iE.pdf.

* cited by examiner

US. Patent Oct. 15, 2013 Sheet 1 0133 US 8,560,130 B2

Actively Controlled

LoC

Purely Passive LoC

Large-scale Moderate Complexity

Simple Complexity

Figure 1

83x0 298G

l l l l l l l l l

Fixed LoC Deslgn n

Fixed LoC Design 1

Reconfigurable Emulation Environment - - - a

Figure 2a

moBAO 298G

l

l

l

l

l

Reconfigurable LoC

Reconfigurable Emulation Environment - — — — — — — — — — — 4

Fixed LoC Deslgn n

Fixed LoC Deslgn 1

Figure 2b

US. Patent Oct. 15, 2013 Sheet 2 0f 33 US 8,560,130 B2

_ . . _ _ . . _ . . _ . . _ . . _ . . _ . . _ Sufficient market size

a, I to justify 3', I ‘ manufacturing costs H — - - — -' - - - — - - — - - — - - —'- - — - - — Sufficient market size

% ‘ : +- ‘ ‘ : ‘ to justify g ‘ i ‘ ‘ : l ‘ l ‘ I‘ : l ‘ creditable R&D costs

I l l l l |l|‘:‘|l‘:‘|‘|:‘|‘l::‘|:||:||| Candidate Lab-on-a-Chip Applications

Figure 3a

Type 1 Type 3 Type 5 Recon?gurable Reconfigurable Reconfigurable l-ab-on-a-chlp Type 2 Lab-on-a-Chip Type 4 Lab-on-a-Chip

Recon?gurable Reconfigurable Nb-on-a-CMLab-on-a-Chip _ . . _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ Sufficient market size

a: tojustify 5 l ‘ manufacturing costs H _ . . _ . ' . . _ . . _ . . _ . . _ _' _ _ _ _ _ Sufficient market size

% ‘ ‘ ‘ I ‘ tojustify E ‘ I ‘ ‘ I : ‘ I ‘ ‘ I ‘ l I ‘ creditable R&D costs

iliAlAllAlAlAilAiAill lll.l.l. Candidate Lab-on-a-Chip Applications

Figure 3b

Sufficient market size

- _ - - - Sufficient market size

to justify creditable R&D costs

Type 1 Type 3 W99 5 Reconfigurable Reconfigurable ReCOnflgurable Lab-on-a-Chip Type 2 Lab-on-a-Chip Type 4 Lab-on-a-Chlp

iegon?gura?le Reconfigurable a 'on'a'c 'p Lab-on-a-Chip

Figure 3c


/ /Reconfigurable \ ' LoC Type 3 , // Reconfigurable

,4--\\_\ LoCType5 , I / I \ \ l l /

_\ Reconf|gura le \‘ - '

\ LoC Type 4 I’ \ I \ /

\

\ Reconfigurable ‘ \ / - _ Reconf|gurabl /\ LOC Typez l\ LoC Type 1

Figure 3d

// Recon?gurable\\ /’ Recon? \\ , - - _ \ gurable

/ / z c \ LOC Type 3 ‘ ' LoC Type 5 ,'

,’ Recon?gurame \‘ Reconfigurable\ \ \ I / / \ \ / / ’

‘\ LoC Type 1 I LOC Type 2 ~ _ - Refogqgura‘ble “ ' T I \ \ o ype

Figure 3e

/, _ \ I, Reconfigurable ‘ , Recon?gurable \\ \ LoC Type5

LoC Type 3

Reconfigurable LoC Type 1 LoC Type 4

Reconfigurable LoC Type 6

Figure 3f

Reconfigurable Reconfigurable \\ LOC Type 5 LoC Type 3

Reconfigurabl: LoC Type 1 Reconfigurable

LoC Type 7 configurabl < LoC Type 6

Reconfigurable LoC Type 8

Figure 39

US. Patent 0a. 15, 2013 Sheet 5 0f 33

Imagined

Realized Software Controlled

Reconfigu_r le Emul Sys

Figure 5

US 8,560,130 B2


|_ — — — — — — _l I _ _ _ _ _ _ __I

l l

I Models Visualization I I I l l

M. II .d. + I Table-Scale I Actual-Scale I Dyna??fgs L|I/'|O'ge|s I LoC Process I Physical LoC I

Emulatlon | System I Sensor Models _>SImuIatIOn I I I

Reaction Models —> I I I Physics Models —> I 'L _ _ _ _ _ _ _ _J

|_ _ _ _ _ _ _ J Hardware

Driver Driver Driver

Configuration Process Control

Software SCrIptS: C) _ _ _ C:

Figure 6a

F _ — — — — 1 r “““ “1

I Models Visualization I I I l l

IVI. II .d. A I Table-Scale I Actual-Scale: Dynag?igs L|I/'|O'ge|s I LoC Process | Physical LoC | SensoIModeIs Emulatlon I System I

_ ' Simulation I I I Reactlon Models—> I I

I Physics Mode|s—> I 'L _ _ _ _ _ _ _ _J'

A l_ _ _ _ _ J Hardware

Driver Driver Driver

l l

Configuration Process Control Control

Software SCrIptSI C) _ _ _ C)

Figure 6b

US. Patent 0a. 15, 2013 Sheet 8 0f 33 US 8,560,130 B2

LCD Alphanumeric Display

|2c Bus Loop-Through 0

® 3 O O SPDT Valve

@ o 8 8 DD 0 o SPDT Valve

— 0

® (ED 0 o SPDT Valve Serial Port

8 (DD 000 SPDT Valve

Motorized Fluidic Mixer

Mechanical Power Clamp Motorized Port Orientation Fluidic

Mixer

Figure 8a term

i ________ “i i ____ “i T“ “i I

mterfaCe, Chemical Chemical Chemical Computer or Process Process Process

Figure 8b

; --------- --T ------ --T - - - - - - “qr-1%

"net-face, Chemical Chemical Chemical Computer or Process Process Process

Microprocessor 1 2 N

Figure 8c

US. Patent 0a. 15, 2013

2:1 INPUT 8-VALVE COMPLEX

Species 1 :(X) (X)

Sheet 9 0f 33 US 8,560,130 B2

®® @

Figure 9a

n:1 INPUT 11-VALVE COMPLEX

Liquid Solvent —>(X)—‘ c 3

Cleaning Gas WJ C 90 91

Figure 10a

@4— Clearing Gas

92 9n

n

SELECTION OUT

US. Patent 0a. 15, 2013 Sheet 11 0133 US 8,560,130 B2


Solvent

GAS

Figure 10b

US. Patent 0a. 15, 2013 Sheet 13 0f 33

n : n INPUT 14-VALVE COMPLEX

Species 1 Species 2 Species n

o o o

f f f 1 91 2 92 " 9n

0 o 0

C1 C2 cn

US 8,560,130 B2

—(Z)


4 : 4 INPUT 14-VALVE COMPLEX

Figure 11b

US. Patent Oct. 15, 2013 Sheet 15 0f 33


7400 T|P122 T;

US 8,560,130 B2

2

i T|P122 El IEI 740422k

___ T m

F 1 2.2k

@

2.2K

GAS 13 11 mw/Llg F 2.2k 2 NW\— +12 >14 3B4

Figure 110


Figure 12c


4:1 INPUT TANDEM VALVE COMPLEX

Liquid Solvent —>®— Cs

Cleaning Gas W C

Drying Gas —>®_ c

Reaction Chamber

Figure 13a

4:1 TANDEM OUTPUT VALVE COMPLEX

Reaction Chamber

Product 1

roduct 2

Product 3

Cleaning Outlet

Figure 14a

(12) ulllted states patent (10) patent n0.: us 8,560,130 b2 ludwig...

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