116 Sunday, September 10th (5:20)

Concurrent Symposium XXII: Experimental Nanomedicine

Synthetic nanopores for bio-molecular analysis

Dimitrov V, Dimauro E, Grinkova YV, Sligar S, Schulten K, Aksimentiev A,

Timp G, University of Illinois, Urbana, Illinois, USA

We describe a prospective strategy for reading the encyclopedic information

encoded in the genome: using a nanopore in a membrane formed from an

MOS-capacitor to sense the charge distribution in a single molecule of

DNA. In principle, as DNA permeates the capacitor-membrane through the

pore, the electrostatic charge distribution polarizes the capacitor and

induces a voltage on the electrodes that can be measured. Double-stranded

DNA is a highly charged, unusually stiff polymer, and so the nano-

electromechanics of DNA during the translocation of the molecule through

the pore profoundly affect the design of this detector. So, first we explored

the electromechanical properties of DNA using an electric field to force

single molecules through synthetic nanopores in ultra-thin silicon mem-

branes. At low electric fields E b200 mV/10 nm, we observed that single

stranded DNA can permeate pores with a radii z0.5 nm, while double-

stranded DNA only permeates pores with a radius z1.5 nm because the

diameter of the double helix is about 2 nm. For pores b1.5 nm-radius, we

find a threshold for permeation of double stranded DNA that depends on

the electric field and pH. For a 1 nm-radius pore, the threshold is E i3.1 V/10 nm at pH=8.5, which we suppose corresponds to the stretching

transition in DNA. The threshold field decreases as pH becomes more

acidic, consistent with the destabilization of the double helix, implying that

double-stranded DNA melts during an electric field-driven translocation

through a 1 nm-radius pore. These observations provide us with the

opportunity to control the translocation kinetics through the pore.

Gregory Louis Timp received his Ph.D. in Electrical

Engineering from the Massachusetts Institute of

Technology. He joined Bell Laboratories in 1988,

where he pursued nanostructure physics. As part of

one collaboration, he investigated low temperature

transport in electron waveguides; high mobility nano-

structures so short that the transport is ballistic. In

another effort, he explored the use of optical traps and

laser focusing of single atoms for lithography appli-

cations. In 2000, he joined the Electrical and Computer Engineering

Department at the University of Illinois. Since then he is been involved in

research applying semiconductor nanotechnology to the study of biology.

doi:10.1016/j.nano.2006.10.128

117 Sunday, September 10th (5:45)

Concurrent Symposium XXII: Experimental Nanomedicine

Supported membrane configuration: a versatile model for deciphering

lipid-protein interplay at cellular membranes

Parikh A, Department of Applied Science, University of California, Davis,

California, USA

Supported membranes represent an elegant route to designing well-defined

fluid interfaces which mimic many physical-chemical properties of

biological membranes. In conjunction with micro- and nanofabrication,

they allow systematic experiments for developing a quantitative under-

standing of structure-dynamics-function relations at cellular membranes as

well as furnish membrane-mimetic devices (e.g., biosensors). This talk will

present examples from our current research to illustrate the development

and application of the supported membrane configuration in deciphering

lipid-lipid and lipid-protein interactions. In particular, we present new

experimental approaches to approximate chemical heterogeneities (choles-

terol-rich nanodomains), curvatures, and rectified dynamics in supported

membrane configuration and explore its applications in the context of

cellular apoptosis.

Atul N. Parikh, is an Associate Professor of applied

science at the University of California, Davis. He

received his B.Chem. Eng. degree from the University

of Bombay (UDCT) and Ph.D. degree from the

Materials Science department at the Pennsylvania

State University. Earlier, he was a postdoctoral

scholar and then a technical staff member at Los Alamos National

Laboratory from 1996 to 2001. His present research interests include

molecular and mesoscale self-assembly, physical chemistry of surfaces,

phase transitions and cooperative processes, nanoscale phenomena, and

biomolecular spectroscopy spanning soft condensed matter, membrane

biophysics, and cell biology.

doi:10.1016/j.nano.2006.10.129

118 Sunday, September 10th (6:10)

Concurrent Symposium XXII: Experimental Nanomedicine

Performance limits of nanobiosensors: elementary considerations and

interpretation of experimental data

Alam MA, Nair P, Purdue University, West Lafayette, Indiana, USA

Modern methods of detection of biomolecules for differential genome

sequencing, protein recognition, etc. rely on variety of chemical and

optical methods to indicate the conjugation of target biomolecules with the

capture probes. Although these classical methods are widely used,

extremely sophisticated and very reliable, and they form the basis of a

industry with billions of dollars of revenue, the techniques are expensive

and cumbersome. Therefore, replacement of the classical techniques with

less expensive approaches that rely on electronic (rather than chemical)

detection of biomolecules has been one of the grand challenges of

biotechnology and electronics. The new techniques are based on the fact

that biomolecules (e.g., DNA, cancer markers, etc.) have definite charge-

states depending on the pH of the surrounding environment, therefore the

conjugation of these molecules with capture probes would modulate the

current flow between source and drain of a transistor, thereby flagging

the conjugation and identifying the molecule (for capture probes with

known sequences). Insulated-gate field Effect transistors (ISFET, circa

1970) has been the earliest known examples of such electronic detection

schemes. This generation of electronic detectors, however, failed to

compete with chemical detection methods. It has suggested recently that a

new generation of surround-gate FETs (e.g., Si-NW and CNT, etc.) will do

better: indeed, there are many recent reports of extraordinary sensitivity,

response time, and selectivity of these new sensors. Although it is broadly

accepted that the Si-NW should have better sensitivity that those of ISFET

and Chem-FETs, the origin of the extraordinary sensitivity remains poorly

understood. The standard interpretation of better electrostatic coupling of

reduced-geometry devices appears reasonable - but a closer analysis

suggests that it would only explain a factor of 2–5 improvement in

sensitivity, not 2–4 orders of magnitude improvement in sensitivity that

have been observed in experiments. In this talk, we use classical diffusion-

capture (D–C) model to suggest that it is the bgeometry of diffusionQrather than bgeometry of electrostaticsQ this is responsible for this

remarkable improvement in sensor performance. We establish a scaling-

law (based on the solution of the D–C model) to interpret experiments to

date within a simple coherent framework. Our scaling laws resolve many

classical puzzles and provide guidance of future design of sensors for

improved sensitivity.

Abstracts / Nanomedicine: Nanotechnology, Biology, and Medicine 2 (2006) 269–312310