'Nanoshells' Meter Measures pH in Living Cells

Using unique nanoparticles that convert laser light into useful information, scientists have created the first nanosized pH meter. The discovery presents biologists with the first potential means of measuring accurate pH changes in real-time, inside living tissue and cells, which could provide non-invasive "optical biopsies" of tumors.

"Almost every biologist I speak with comes up with one or two things they'd like to measure with this," said lead researcher and Rice University chemistry professor Naomi Halas, the Stanley C. Moore Professor of Electrical and Computer Engineering and director of Rice's Laboratory for Nanophotonics (LANP).

The new pH meter may be useful in determining whether or not some cancer tumors are malignant. With current methods, a piece of the tumor would need to be physically removed via biopsy -- a painful and invasive procedure -- and visually evaluated under a microscope. Halas said LANP's new nano pH meter could be used instead to measure the pH inside the tumor with nothing more invasive than an injection.

The term "pH" was coined by the Danish chemist Søren Sørensen in 1909 as a way of expressing a solution's acidity. pH ranges from 1 (the most acidic) to 14 (the most alkaline).

Halas's LANP team created the pH sensor using nanoshells, optically tuned nanoparticles invented by Halas. Each nanoshell contains a tiny core of non-conducting silica that's covered by a thin shell of metal, usually gold. Many times smaller than living cells, nanoshells can be produced with great precision and the metal shells can be tuned to absorb or scatter specific wavelengths of light.

To form the pH sensor, Halas' team coated the nanoshells with pH-sensitive molecules called paramercaptobenzoic acid, or pMBA. When placed in solutions of varying acidity and illuminated, the nanoshell-molecule device provides small but easily detectable changes in the properties of the scattered light that, when "decoded," can be used to determine the pH of the nanodevice's local environment to remarkably high accuracy.

False-color electron microscopy image of nanoshells magnified 15,000 times.

Inspired by techniques normally applied to image recognition, the team formulated an efficient statistical learning procedure to produce the device output, achieving an average accuracy of 0.1 pH units.

Co-authors of the paper, which has been published online in the journal Nano Letters, include postdoctoral researchers Sandra Bishnoi, now an assistant professor at the Illinois Institute of Technology, and Muhammed Gheith; graduate students Christopher Rozell and Carly Levin; Bruce Johnson, distinguished faculty fellow of chemistry and executive director of the Rice Quantum Institute; and Don Johnson, J.S. Abercrombie Professor of Electrical and Computer Engineering and Statistics.

The research was supported by the Department of Defense's Congressionally Directed Medical Research Program, the Air Force Office of Scientific Research, the Keck Foundation, the Robert A. Welch Foundation and Texas Instruments. For more information, visit: www.rice.edu