Peak force infrared microscopy for label-free chemical imaging at sub 10 nm spatial resolution

Author(s):  
Le Wang ◽  
Guanghong Zeng ◽  
Gilbert C. Walker ◽  
Xiaoji Xu
2016 ◽  
Vol 2 (9) ◽  
pp. e1600521 ◽  
Author(s):  
Delong Zhang ◽  
Chen Li ◽  
Chi Zhang ◽  
Mikhail N. Slipchenko ◽  
Gregory Eakins ◽  
...  

Chemical contrast has long been sought for label-free visualization of biomolecules and materials in complex living systems. Although infrared spectroscopic imaging has come a long way in this direction, it is thus far only applicable to dried tissues because of the strong infrared absorption by water. It also suffers from low spatial resolution due to long wavelengths and lacks optical sectioning capabilities. We overcome these limitations through sensing vibrational absorption–induced photothermal effect by a visible laser beam. Our mid-infrared photothermal (MIP) approach reached 10 μM detection sensitivity and submicrometer lateral spatial resolution. This performance has exceeded the diffraction limit of infrared microscopy and allowed label-free three-dimensional chemical imaging of live cells and organisms. Distributions of endogenous lipid and exogenous drug inside single cells were visualized. We further demonstrated in vivo MIP imaging of lipids and proteins inCaenorhabditis elegans. The reported MIP imaging technology promises broad applications from monitoring metabolic activities to high-resolution mapping of drug molecules in living systems, which are beyond the reach of current infrared microscopy.


2020 ◽  
Author(s):  
Haomin Wang ◽  
Joseph M. González-Fialkowski ◽  
Wenqian Li ◽  
Yan Yu ◽  
Xiaoji Xu

Atomic force microscopy-infrared microscopy (AFM-IR) provides a route to bypass Abbe’s diffraction limit through photothermal detections of infrared absorption. With the combination of total internal reflection, AFM-IR can operate in the aqueous phase. However, AFM-IR in contact mode suffers from surface damage from the lateral shear force between the tip and sample, and can only achieve 20~25-nm spatial resolution. Here, we develop the liquid-phase peak force infrared (LiPFIR) microscopy that avoids the detrimental shear force and delivers an 8-nm spatial resolution. The non-destructiveness of the LiPFIR microscopy enables <i>in situ</i> chemical measurement of heterogeneous materials and investigations on a range of chemical and physical transformations, including polymer surface reorganization, hydrogen-deuterium isotope exchange, and ethanol-induced denaturation of proteins. We also perform LiPFIR imaging of the budding site of yeast cell wall in the fluid as a demonstration of biological applications. LiPFIR unleashes the potential of in liquid AFM-IR for chemical nanoscopy.


2020 ◽  
Author(s):  
Haomin Wang ◽  
Joseph M. González-Fialkowski ◽  
Wenqian Li ◽  
Qing Xie ◽  
Yan Yu ◽  
...  

Atomic force microscopy-infrared microscopy (AFM-IR) provides a route to bypass Abbe’s diffraction limit through photothermal detections of infrared absorption. With the combination of total internal reflection, AFM-IR can operate in the aqueous phase. However, AFM-IR in contact mode suffers from surface damage from the lateral shear force between the tip and sample, and can only achieve 20~25-nm spatial resolution. Here, we develop the liquid-phase peak force infrared (LiPFIR) microscopy that avoids the detrimental shear force and delivers an 8-nm spatial resolution. The non-destructiveness of the LiPFIR microscopy enables <i>in situ</i> chemical measurement of heterogeneous materials and investigations on a range of chemical and physical transformations, including polymer surface reorganization, hydrogen-deuterium isotope exchange, and ethanol-induced denaturation of proteins. We also perform LiPFIR imaging of the budding site of yeast cell wall in the fluid as a demonstration of biological applications. LiPFIR unleashes the potential of in liquid AFM-IR for chemical nanoscopy.


2009 ◽  
Vol 48 (47) ◽  
pp. 8798-8798
Author(s):  
Marianne���H.���F. Kox ◽  
Katrin���F. Domke ◽  
James���P.���R. Day ◽  
Gianluca Rago ◽  
Eli Stavitski ◽  
...  

2009 ◽  
Vol 121 (47) ◽  
pp. 9152-9156 ◽  
Author(s):  
Marianne���H.���F. Kox ◽  
Katrin���F. Domke ◽  
James���P.���R. Day ◽  
Gianluca Rago ◽  
Eli Stavitski ◽  
...  

2009 ◽  
Vol 121 (47) ◽  
pp. 8956-8956
Author(s):  
Marianne���H.���F. Kox ◽  
Katrin���F. Domke ◽  
James���P.���R. Day ◽  
Gianluca Rago ◽  
Eli Stavitski ◽  
...  

2017 ◽  
Vol 53 (53) ◽  
pp. 7397-7400 ◽  
Author(s):  
Le Wang ◽  
Dandan Huang ◽  
Chak K. Chan ◽  
Yong Jie Li ◽  
Xiaoji G. Xu

Individual fine particulate matter (PM2.5) particles are revealed with mechanical mapping and infrared imaging at 10 nm spatial resolution.


2009 ◽  
Vol 48 (47) ◽  
pp. 8990-8994 ◽  
Author(s):  
Marianne���H.���F. Kox ◽  
Katrin���F. Domke ◽  
James���P.���R. Day ◽  
Gianluca Rago ◽  
Eli Stavitski ◽  
...  

2019 ◽  
Author(s):  
Le Wang ◽  
Devon Jakob ◽  
Haomin Wang ◽  
Alexis Apostolos ◽  
Marcos M. Pires ◽  
...  

<div>Infrared chemical microscopy through mechanical probing of light-matter interactions by atomic force microscopy (AFM) bypasses the diffraction limit. One increasingly popular technique is photo-induced force microscopy (PiFM), which utilizes the mechanical heterodyne signal detection between cantilever mechanical resonant oscillations and the photo induced force from light-matter interaction. So far, photo induced force microscopy has been operated in only one heterodyne configuration. In this article, we generalize heterodyne configurations of photoinduced force microscopy by introducing two new schemes: harmonic heterodyne detection and sequential heterodyne detection. In harmonic heterodyne detection, the laser repetition rate matches integer fractions of the difference between the two mechanical resonant modes of the AFM cantilever. The high harmonic of the beating from the photothermal expansion mixes with the AFM cantilever oscillation to provide PiFM signal. In sequential heterodyne detection, the combination of the repetition rate of laser pulses and polarization modulation frequency matches the difference between two AFM mechanical modes, leading to detectable PiFM signals. These two generalized heterodyne configurations for photo induced force microscopy deliver new avenues for chemical imaging and broadband spectroscopy at ~10 nm spatial resolution. They are suitable for a wide range of heterogeneous materials across various disciplines: from structured polymer film, polaritonic boron nitride materials, to isolated bacterial peptidoglycan cell walls. The generalized heterodyne configurations introduce flexibility for the implementation of PiFM and related tapping mode AFM-IR, and provide possibilities for additional modulation channel in PiFM for targeted signal extraction with nanoscale spatial resolution.</div>


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