Colloidal quantum dots, viruses, DNA and all other nanoparticles have acoustic vibrations that can act as 'fingerprints' to identify their shape, size and mechanical properties, yet high-resolution Raman spectroscopy in this low-energy range has been lacking. Here, we demonstrate extraordinary acoustic Raman (EAR) spectroscopy to measure the Raman-active vibrations of single isolated nanoparticles in the 0.1-10 cm −1 range with ∼0.05 cm −1 resolution, to resolve peak splitting from material anisotropy and to probe the low-frequency modes of biomolecules. EAR employs a nanoaperture laser tweezer that can select particles of interest and manipulate them once identified. We therefore believe that this nanotechnology will enable expanded capabilities for the study of nanoparticles in the materials and life sciences.T he interaction of light with mechanical vibrations has had great impact in two disparate regimes, which are typified by the sub-gigahertz cavity optomechanics of micrometresized structures 1 and the super-terahertz Raman spectroscopy of molecular vibrations 2 . Between these frequencies, there is a gap where new technologies are desired. This gap is crucial to nanotechnology, because it contains the acoustic regime of nanoparticles, and therefore contains valuable information about their specific size, shape and material properties. A wide range of nanoparticles have acoustic vibrations in this frequency window, including colloids 3 , quantum dots 3 , proteins 4 , DNA 5 and virions. To identify the properties of these nanoparticles, it is desirable to have an ultra-sensitive, low-frequency approach to Raman spectroscopy with high spectral resolution.To date, the spectral identification of nanoparticles using conventional Raman spectroscopy has been unfeasible due to its limited spectral resolution, which is typically 1 cm −1 in high-resolution systems. Furthermore, elastic scattering from the excitation laser source should be filtered out, which typically limits the minimum frequency of vibrations to above 10 cm −1 . For the most part, only nanoparticles smaller than 10 nm can have their acoustic vibrations probed with conventional Raman spectroscopy 6 . Yet many particles of interest, such as virions and colloidal particles, are larger than 10 nm. Moreover, smaller particles that are not as stiff, especially biomaterials such as proteins and DNA oligomers, have large-scale vibration modes around 100 GHz (ref. 7), as will be shown here. It is this region in particular that we will address in this Article-particles on the order of 10 nm, with resonances in the range of 0.7-10 cm −1 . However, the technique may be extended to a broader range of particle sizes and frequencies in a straightforward manner. Although past Raman experiments have looked at large numbers of nanoparticles simultaneously 8 , here we observe the Raman-active modes in a solution of single nanoparticles trapped by a laser tweezer. We note, however, that this is not the first demonstration of single-particle sensitivity with Raman spect...

Nanoaperture optical tweezers are emerging as useful label-free, free-solution tools for the detection and identification of biological molecules and their interactions at the single molecule level. Nanoaperture optical tweezers provide a low-cost, scalable, straight-forward, high-speed and highly sensitive (SNR ∼ 33) platform to observe real-time dynamics and to quantify binding kinetics of protein-small molecule interactions without the need to use tethers or labeling. Such nanoaperture-based optical tweezers, which are 1000 times more efficient than conventional optical tweezers, have been used to trap and isolate single DNA molecules and to study proteins like p53, which has been claimed to be in mutant form for 75% of human cancers. More recently, nanoaperture optical tweezers have been used to probe the low-frequency (in the single digit wavenumber range) Raman active modes of single nanoparticles and proteins. Here we review recent developments in the field of nanoaperture optical tweezers and how they have been applied to protein-antibody interactions, protein-small molecule interactions including single molecule binding kinetics, and protein-DNA interactions. In addition, recent works on the integration of nanoaperture optical tweezers at the tip of optical fiber and in microfluidic environments are presented.

We trap a set of molecular weight standard globular proteins using a double nanohole optical trap. The root mean squared variation of the trapping laser transmission intensity gives a linear dependence with the molecular weight, showing the potential for analysis of globular proteins. The characteristic time of the autocorrelation of the trapping laser intensity variations scales with a -2/3 power dependence with the volume of the particle. A hydrodynamic laser tweezer model is used to explain these dependencies. Since this is a single particle technique that operates in solution and can be used to isolate an individual particle, we believe that it provides an interesting alternative to existing analysis methods and shows promise to expand the capabilities of protein related studies to the single particle level.

We use a double nanohole (DNH) optical tweezer with two trapping lasers beating to excite the vibrational modes of single-stranded DNA (ssDNA) fragments in the extremely high frequency range. We find the resonant vibration frequency of a 20 base ssDNA to be 40 GHz. We show that the change in the resonant frequency for different lengths of the DNA strand is in good agreement with one dimensional lattice vibration theory. Thus the DNH tweezer system could distinguish between different lengths of DNA strands with resolution down to a few bases. By varying the base sequence and length, it is possible to adjust the resonance frequency vibration spectrum. The technique shows the potential for use in sequencing applications if we can improve the resolution of the present system to detect changes in resonant frequency for a single base change in a given sequence. The technique is single-molecule and label-free as compared to the existing methods used for DNA characterization like gel electrophoresis.

The sensitivity of infrared (IR) focal plane arrays (FPAs) is often limited by a low pixel fill factor. Solid immersion microlens arrays address this problem by focusing the light reaching each pixel into the most sensitive part of that pixel. This strategy is used in CMOS image sensors but has not been industrially adopted for IR FPAs due to significant difficulties in integration with compound semiconductors. Here, we present an all-in-one solution for producing solid immersion microlens arrays compatible with various IR FPAs regardless of their substrate material. Our strategy is to use refractive lenses made of SiO 2 and Si 3 N 4 with very broad-band and efficient focusing abilities. Notably, our strategy works across a broad range of wavelengths with little performance degradation, meaning it is scalable to various applications. We implemented our method in short-wavelength IR FPAs and demonstrated 7.4 times improvement in quantum efficiency. This is the first demonstration of an immersion microlens array in a non-silicon infrared FPA.