Aspects of the present invention include systems and devices useful for surface chemical analysis of solid samples by Tip Enhanced Raman Spectrometry (TERS), and particularly it relates to devices useful for chemical analysis of molecular compounds located either on or within thin surface layer of solid samples. Even more particularly, aspects of the present invention relate to systems, and devices for non-destructive analysis combining both high sensitivity and high spatial resolution of analysis of chemical compounds located or distributed on the surface of solid samples with obtaining important information regarding vibration spectra of atoms and molecular groups contained in a thin surface layer of solid samples. These objectives are realized by implementation of computer-assisted systems that use sensors to carefully regulate the motion of, and force applied to, probes of atomic force microscopes.

Described herein is the analysis of nanomechanical characteristics of cells. In particular, changes in certain local nanomechanical characteristics of ex vivo human cells can correlate with presence of a human disease, such as cancer, as well as a particular stage of progression of the disease. Also, for human patients that are administered with a therapeutic agent, changes in local nanomechanical characteristics of ex vivo cells collected from the patients can correlate with effectiveness of the therapeutic agent in terms of impeding or reversing progression of the disease. By exploiting this correlation, systems and related methods can be advantageously implemented for disease state detection and therapeutic agent selection and monitoring.

A scanning probe microscope capable of controlling a decrease of the resolution of an objective lens disposed in the scanning probe microscope, and capable of easily carrying out the adjustment of an optical axis of an optical lever using the objective lens. The scanning probe microscope includes: a cantilever having a probe; a light source part radiating beams; a first reflective part reflecting an incident beam (L0) and guiding the incident beam to a reflective surface; a light receiving part receiving the beams; a second reflective part reflecting a reflected beam (L1) and guiding the reflected beam to the light receiving part; and an objective lens disposed to face the cantilever and adopted to observe and capture an area around the cantilever, the objective lens having the number of openings of NA, wherein the first reflective part is disposed at a position between the objective lens and the cantilever.

System and method for measuring an optical property of a sub micrometer region of a sample including interacting a probe tip of a probe microscope with a region of the sample, illuminating the sample with a beam of light from a radiation source such that light is scattered from the probe-sample interaction region, interfering a reference beam with the scattered light wherein the reference beam has an adjustable optical phase, measuring with a detector at least a portion of the light scattered from probe-sample and background regions at a substantially constant reference phase, and constructing a signal indicative of the optical property of the sample wherein contributions from background scattered light are substantially suppressed.

An optical output system includes: a first laser that outputs first light which is a pulse laser in response to input of a first signal; a second laser that outputs second light which is a pulse laser in response to input of a second signal; and an arithmetic unit that inputs the first signal and the second signal to the first laser and the second laser, wherein the arithmetic unit repeatedly inputs the first signal and the second signal with switching a variable delay value, which is a difference between a timing to input the first signal to the first laser and a timing to input the second signal to the second laser, in a plurality of ways.

The invention provides a nanoantenna scanning probe tip for microscropy or spectroscopy. The nanoantenna scanning probe tip includes a sharp probe tip covered with a contiguous film of predetermined sized and shaped plasmonic nanoparticles. A method for forming the nanoantenna scanning probe tip by trapping nanoparticles having a predetermined size and shape at a liquid surface using surface tension, forming a uniform and organized monolayer film on the liquid surface, and then transferring portions of the film to a sharp probe tip. In preferred embodiments, the sharp probe tip is one of a conductive STM (scanning tunneling microscopy) tip, a tuning fork tip or an AFM (atomic force microscopy) tip. The sharp tip can be blunted with an oxide layer.

Methods and apparatus for characterizing a sample in situ as to both its mechanical and optical characteristics. The apparatus comprises a reflective microscope with a concave primary mirror and a convex secondary mirror sharing a common optical axis, and an actuator vignetted by the convex secondary mirror for applying a force to a nanoprobe in a direction having a component along the common optical axis. The apparatus may addition include a source for generating an illuminating beam, a detector, and a processor for forming an image based on a signal provided by the detector.

The invention relates to a measuring device and a method for determining mass and/or mechanical properties of a biological system.

Aspects of the present invention include systems, devices, and methods of surface chemical analysis of solid samples, and particularly it relates to methods of chemical analysis of molecular compounds located either on or within thin surface layer of solid samples. Even more particularly, aspects of the present invention relate to systems, devices, and non-destructive methods combining both high sensitivity and high spatial resolution of analysis of chemical compounds located or distributed on the surface of solid samples with obtaining most important information regarding vibration spectra of atoms and molecular groups contained in thin surface layer of solid samples. These objectives are realized by implementation of computer-assisted systems that carefully regulate the motion of, and force applied to probes of atomic force microscopes.

Atomic force microscope measuring device comprising a micro-cantilever and an intensity modulated laser exciting the cantilever, wherein the measuring device comprises an optical microscope, in particular a fluorescence microscope, a confocal microscope, a fluorescence energy transfer (FRET) microscope, a DIC and/or phase contrast microscope, all of those in particular construed as an inverted microscope.