Apparatus and method for sizing nanoparticles based on optical forces and interferometric field detection

Abstract

Light from a laser source is split into a reference arm and a detection arm. The light in the detection arm is focused into a channel containing particles to be detected and is backscattered by the particles. The light in the reference arm is attenuated. The attenuated and backscattered light are caused to interfere and detected by a split detector so that the effects of background light can be subtracted out, while the backscattered light is detected to detect the particles.

Description

REFERENCE TO RELATED APPLICATION [0001] The present application claims the benefit of U.S. Provisional Patent Application No. 60 / 677,411, filed May 4, 2005, whose disclosure is hereby incorporated by reference in its entirety into the present disclosure.STATEMENT OF GOVERNMENT INTEREST [0002] The work leading to the present invention was supported by NSF Grant No. PHS-0441964 and DARPA Grant No. MDA972-00-1-0021. The government has certain rights in the invention.FIELD OF THE INVENTION [0003] The present invention is directed to a technique for the detection of nanoparticles, such as viruses, and more particularly to an optical technique using interferometry which lessens the dependence on particle radius relative to known techniques. DESCRIPTION OF RELATED ART [0004] Particles with characteristic sizes of less than 100 nm are becoming increasingly important in the context of nanoscience and technology. Applications range from solid-state physics to biology. For example, semiconduct...

AI Technical Summary

Benefits of technology

[0010] To achieve the above and other objects, the present invention is directed to a background-free detection approach which gives us unsurpassed real-time detection sensitivity for nanoscale particles. We demonstrate the successful detection and classification of low-index particles such as individual viruses carried in a microfluidic system. In the current version, we are able to detect individual water-solubilized polymer particles of 10 nm radius within a few milliseconds. Our detection scheme is well suited for the screening and sorting of various nanoscale particles such as viruses and larger proteins and is compatible with current microfluidic technology.

[0012] The invention provides a background-free, interferometric detection technique for nanoscale particles. The detector works in real time and with single particle sensitivity. Interferometric detection ensures that the signal amplitude scales with the third power of particle size, and the use of a split detector ensures the best possible signal-to-noise ratio, independent of laser power noise. Within a one-millisecond time window we are able to reliably detect a single 10 nm polystyrene particle or a single 5 nm gold particle. Even higher sensitivity could be achieved by modulating the reference beam length (phase modulation) or by heterodyne detection. The detection scheme will find applications in a variety of fields such as particle tracking inside cells, detection of biowarfare agents (viruses), contamination control of water and air, and others. The detector can also be used as a prescreening stage in a larger biodetector assembly for deciding whether a subsequent one-shot detector stage with high chemical specificity (antigenantibody, polymerase chain reaction, laser spectroscopy, etc.) should be exposed or not.

Problems solved by technology

Because of their small size, nanoparticles are not easy to detect, and it is evident that there is high demand in novel techniques for the reliable detection, characterization, sorting, and tracking of nanoscale particles of various sorts.

It has been determined that the inhalation of ultrafine particles originating from emissions of various kinds can cause heritable mutations.

Furthermore, as the feature size of integrated circuits becomes increasingly smaller, contamination control of ultrafine particles poses a challenge for the semiconductor industry.

However, the detection of single nanoparticles is a challenging task which, so far, has been only accomplished by indirect means, i.e., by fluorescent labeling or immobilization on a surface and subsequent analysis with dark field microscopy.

It has been recognized that current real-time single particle detection methods for micrometer-sized particles are not suitable for nanoparticle detection because the intensity of light scattering scales with the sixth power of particle size.

Although these methods extend the detection sensitivity to smaller particle sizes, they suffer from other shortcomings which prevent the detection of single nanoparticles in real time.

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