Biology Meets Engineering: Communica5on Between Fields. Mark A. Stremler Associate Professor Engineering Science and Mechanics

Transcription

1 Biology Meets Engineering: Communica5on Between Fields Mark A. Stremler Associate Professor Engineering Science and Mechanics

2 The star9ng point What does it mean for Biology and Engineering to Meet?

3 Case Study: Microfluidics for cellular scale analysis Engineering tools for biological discovery

4 Typical fabrica9on of a microfluidic device using sod lithography

5 Fluid mixing for high throughput genomic and proteomic analysis McQuain, Seale, Peek, Fisher, Levy, Stremler & Haselton, Chao9c mixer improves microarray hybridiza9on, Analy&cal Biochemistry 325(2), (2004). surface: standard 7.5 cm x 2.5 cm glass microarray a single spot contains probe molecules of the same type side view targets probes probes: targets: molecules of unknown sequence or type suspended in hybridization solution targets hybridize with complementary probes, binding them in place based on sequence targets are identified by binding location molecules of known sequence or type immobilized on surface in an array of spots microarrays can contain over 10,000 unique probe spots results depend on achieving the necessary target probe interactions

6 An engineering approach to mixing reduces variability and increases sensi9vity Microchannels schematic C A B Syringe pumps Open valves Closed valves D Holes in top plate for sources and sinks Standard microarray analysis relies on diffusion to deliver targets to complimentary probes mixing based analysis 1 hour experiments Fluid mixing chamber Microarray mixing diffusion diffusion based analysis 24 hour experiments Average signal level ng 1 ng 10 ng Target DNA in hybridization solution

7 Cell concentra9on and sor9ng with microscale electric fields McQuain, Seale, Peek, Fisher, Levy, Stremler & Haselton, Chao9c mixer improves microarray hybridiza9on, Analy&cal Biochemistry 325(2), (2004). Need to develop techniques to monitor, detect & remove low levels of microorganisms from water Tradi9onal water analysis methods such as filtra9on involve a lengthy culture step Selec9ve enrichment enhances our ability to detect biological par9cles Toxins!1-10 nm! Protein / molecule Viruses! nm! 1-50 proteins Bacteria! 1-3 µm! proteins Protozoa! 4-10 µm! proteins

8 Live cells are trapped with dielectrophoresis + EP EK - Dielectrophoresis: mo9on of a par9cle due to polariza9on induced by nonuniform electric fields. Integrated arrays of insulators create a nonuniform electric field Live (green) and dead (red) E. coli cells are separated due to differences in membrane integrity Non-uniformities in E-field generated by insulating posts.

9 Suggested Readings I. Meyvantsson & D.J. Beebe, Cell Culture Models in Microfluidic Systems, Annual Reviews in Analy&cal Chemistry :423. Microfluidic technology holds great promise for the crea9on of advanced cell culture models. In this review, we discuss the characteriza9on of cell culture in microfluidic systems, describe important biochemical and physical features of the cell microenvironment, and review studies of microfluidic cell manipula9on in the context of these features. Finally, we consider the integra9on of analy9cal elements, ways to achieve high throughput, and the design constraints imposed by cell biology applica9ons. T.M. Squires & S.R. Quake, Microfluidics: Fluid physics at the nanoliter scale, Reviews of Modern Physics 77:977, Microfabricated integrated circuits revolu9onized computa9on by vastly reducing the space, labor, and 9me required for calcula9ons. Microfluidic systems hold similar promise for the large scale automa9on of chemistry and biology, sugges9ng the possibility of numerous experiments performed rapidly and in parallel, while consuming ligle reagent. While it is too early to tell whether such a vision will be realized, significant progress has been achieved, and various applica9ons of significant scien9fic and prac9cal interest have been developed. Here a review of the physics of small volumes (nanoliters) of fluids is presented, as parametrized by a series of dimensionless numbers expressing the rela9ve importance of various physical phenomena.

10 Case Study: New views on flight Exploi5ng unique biological func5on in engineering design

11 Unsteady aerodynamics of flapping wings for insect flight A. Andersen, U. Pesavento & Z. Jane Wang, Unsteady aerodynamics of flugering and tumbling plates Journal of Fluid Mechanics 541: Z. Jane Wang, Dragonfly flight Physics Today, October 2008, Insect flight at low speeds is quite different from the standard engineering approach to aerodynamic flight. What can we learn from their maneuverability and efficiency? A flat plate model is a simple place to start

12 A freely falling plate exhibits a range of dynamic behaviors chaos flugering tumbling the complex, 9me dependent fluid dynamics plays an important role in the dynamics of the plate

13 Complex, coupled fluid structure interac9ons lead to flight for a dragonfly what wing structure and control algorithm(s) lead to controlled flight under these circumstances?

14 Flying snakes J.J. Socha, T. O Dempsey & M. LaBarbera, A 3 D kinema9c analysis of gliding in a flying snake, Chrysopelea paradisi Journal of Experimental Biology, 208:1817. certain snakes use a flagened rib cage and traveling waves along their bodies to generate lid as they glide through the air

15 Suggested Readings Z.J. Wang, Dissec9ng Insect Flight, Annual Reviews of Fluid Mechanics :183. What force does an insect wing generate? Finding answers to this enduring ques9on is an essen9al step toward our understanding of interac9ons of moving objects with fluids that enable most living species such as insects, birds, and fish to travel efficiently and us to follow similar suit with sails, oars, and airfoils. We give a brief history of research in insect flight and discuss recent findings in unsteady aerodynamics of flapping flight at intermediate range Reynolds numbers (10 104). In par9cular, we examine the unsteady mechanisms in uniform and accelerated mo9ons, forward and hovering flight, as well as passive flight of free falling objects. The results obtained by taking the insects apart helped us to resolve previous puzzles about the force es9mates in hovering insects, to ellucidate basic mechanisms essen9al to flapping flight, and to gain insights about the efficieny of flight. J.J. Socha, Gliding flight in the paradise tree snake, Nature 418:603, Most vertebrate gliders, such as flying squirrels, use symmetrically paired wings to generate lid during flight, but flying snakes (genus Chrysopelea) have no such appendages or other obvious morphological specializa9ons to assist them in their aerial movements. Here I describe the threedimensional kinema9cs of gliding by the paradise tree snake, Chrysopelea paradisi, which indicate that the aerial behaviour of this snake is unlike that of any other glider and that it can exert remarkable control over the direc9on it takes, despite an apparent lack of control surfaces.

16 Case Study: Toward understanding and trea9ng cardiovascular disease Advancing fron5ers of knowledge in biology and engineering

17 Developing engineering tools for understanding cardiovascular behavior R. Kumar, K.C. Stewart, J.J. Charonko, P.P. Vlachos & W.C. Ligle, Diastolic Intraventricular Pressure Gradients Assessed by Color M Mode Echocardiography Circula&on 118(18):S602. Developing velocity and pressure measurement tools for in vivo inves9ga9ons

18 Advances in measurement techniques enable early observa9on of heart disease pressure distribu9ons are determined from experimental velocity measurements new experimental insights are leading to beger characteriza9on of cardiac health

19 Suggested Readings C.A. Taylor & M.T. Draney, Experimental and Computa9onal Methods in Cardiovascular Fluid Mechanics, Annual Reviews of Fluid Mechanics :197. The characteriza9on of blood flow is important for understanding the func9on of the cardiovascular system under normal and diseased condi9ons, designing cardiovascular devices, and diagnosing and trea9ng congenital and acquired cardiovascular disease. Experimental methods, especially magne9c resonance imaging techniques can be used to noninvasively quan9fy blood flow for diagnosing cardiovascular disease, researching disease mechanisms, and valida9ng assump9ons and predic9ons of mathema9cal models. Computa9onal methods can be used to simulate blood flow and vessel dynamics, test hypotheses of disease forma9on under controlled condi9ons, and evaluate devices that have not yet been built and treatments that have not yet been implemented. In this ar9cle we review experimental and computa9onal methods for quan9fying blood flow velocity and pressure fields in human arteries. We place par9cular emphasis on providing an introduc9on to the physics and applica9ons of magne9c resonance imaging, and surveying lumped parameter, one dimensional, and three dimensional numerical methods used to model blood flow.

20 Mark A. Stremler Virginia Tech Engineering Science & Mechanics 333P Norris Hall Blacksburg, VA Thank You!