NTI Core Research Project: Cellular Probes

Project Title: Cellular Probes.  Principal Investigator:  Haim H. Bau, Ph.D., University of Pennsylvania.  Team Members:  Paul Ducheyne, Ph.D., University of Pennsylvania, Yury Gogotsi, Ph.D., Drexel University, and Nae Dun, Ph.D., Temple University.

Project Summary: Cells are the basic building blocks of life.  The ability to sense and modify intracellular processes is important for, among other things, bettering our understanding of biological processes, developing drugs and evaluating their effectiveness, and modifying cell function.  The Cellular Probes Core Group focuses on (i) developing nano-size, integrated, multifunctional probes capable of penetrating a cell’s membrane with minimal intrusion, injecting reagents into the cell, carrying out electrophysiological measurements, and detecting the presence of target analytes; (ii) demonstrating the utility of the probes for medical and pharmaceutical studies; and (iii) generating new knowledge.

One of the core technologies developed by the cellular Probes Group is carbon-based nanopipettes (CNP).  The CNP consists of a glass capillarity lined with a carbon film along its inner surface anad terminating with an exposed carbon pipe whose diameter may vary, depending on process conditions, from 10s to 100s of nanometers.  The probes are fabricated through a process that does not require any assembly.  Being hollow, the probes allow injection of reagents into the cell using standard cell physiology equipment.  Since the probes are conductive, cell penetration can be sensed through an electrical signal.  The probes can also be used for cell electrical measurements concurrently with injection.  The probe’s surface can be functionalized with gold particles, proteins, biomarkers, and oligonucleotides for introduction of analytes into the cell, biosensing, and surface enhanced Raman spectroscopy.

The CNPs enjoy a number of advantages over the commonly used glass pipettes.  They are smaller and less intrusive, flexible yet stiff enough to penetrate through the cell membrane, resistant to breakage and clogging, allow concurrent injection and electrical measurements, and are amenable to automation.

Kim, B.M.; Bau, H.H.; 2005, A Method for Fabricating Integrated Nanostructures and Applications Thereof, Patent Application 20060115971.

Kim, B.M., Murray, T.; and Bau, H.H.; 2005, The Fabrication of Integrated Carbon Pipes with Sub Micron Diameters, Nanotechnology 16, 1317-1320.

Schrlau, M.G.; Falls, E.R.; Ziober, B.L.; Bau, H.H. 2008,  Carbon Nanopipettes for Cell Probes and Intracellular Injection, Nanotechnology 19, 015101.

Schrlau, M.G.; Falls, E.R.; Ziober, B.L.; Bau, H.H. 2008, Carbon Nanopipettes Characterize Calcium Release Pathways in Breast Cancer Cells, to appear in Nanotechnology 19.