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MicroscopyInnovations


2020 Microscopy Today Innovation Awards Charles Lyman, Senior Editor


The editors of Microscopy Today congratulate the 10 winners of the 11th Microscopy Today Innovation Awards


below advance microscopy in the areas of


hyperspectral image stack is acquired to reveal molecular information inside the samples. Previously, phase imaging has been combined with fluo-


competition. The innovations described light


microscopy, electron microscopy, and microanalysis. These innovations will make microscopy and micro- analysis more powerful, more productive, and easier to accomplish.


Bond-Selective Transient Phase Microscope Boston University


Developers: Delong Zhang, Lu Lan, Gabriel Popescu, and Ji-Xin Cheng


In the widely used phase contrast


microscope, the optical phase of pho- tons passing through a sample is largely insensitive to the chemical composition inside, making it difficult to investigate the molecular interactions in complex biological and material systems. Te


new Bond-Selective Transient Phase (BSTP) microscope solves this long-standing bottleneck by probing the transient phase change resulting from the molecular vibrational absorption of a pulsed mid-infrared (IR) excitation. Te BSTP microscope operates in the following manner.


First, a diffraction phase microscope is used to acquire a quantitative phase image of an unperturbed sample, a “cold” frame. Next, mid-IR pulses illuminate the sample, generat- ing absorption and a local temperature rise, which transiently modifies the local refractive index and the quantitative phase image, a “hot” frame. However, the temperature rise lasts only a few microseconds, and thus the phase change cannot be captured with current recording devices operating at only a few thousand frames per second. To achieve sub-micro- second temporal resolution, a time-gated phase imaging scheme captures the phase change resulting from a mid-IR pulse that produces the “hot” frame. Finally, by comparing the “hot” and “cold” phase images, a differential phase image is obtained without the high background signal from water in the sample. Tis differential phase image reveals char- acteristic molecular vibrational effects at chemical bonds. By sweeping the excitation wavelength of mid-IR pulses, a


20 doi:10.1017/S1551929520001364


RCM-NIR Microscope Upgrade Confocal.nl Developer: Erik Manders


Te RCM-NIR module is a


microscope upgrade allowing super- resolution confocal 3D imaging in the near-infrared (NIR) light spectrum (800–1000 nm). Te RCM-NIR allows penetration up to 1 mm deep into the specimen without the need for any spe-


cialized equipment other than a conventional microscope setup with a low-power (non-damaging) laser. Te imaging setup consists of an RCM-NIR upgrade module, a fluorescence micro- scope, a CMOS camera, a laser combiner (785 nm and 640 nm excitation at 20 mW), and broad-spectrum LED illumination. Te RCM-NIR uses Confocal.nl re-scan technology as a


basis. As in a standard confocal microscope, the scanning unit scans the laser light in the sample and de-scans the emission light, directing it at the pinhole. Aſter the pinhole, a second re- scan unit directs the light onto a camera chip. During imaging, the re-scan mirrors move with a larger amplitude than the first scan mirrors. Tis magnifies the image on the camera chip com- pared to the sample and eventually results in the higher resolu- tion of the image. By using a sensitive camera as detector, the signal- to-noise ratio of the RCM is 4 times higher than in stan- dard confocal microscopy. Te camera-based detection scheme


www.microscopy-today.com • 2020 September


rescent labeling to provide molecular specificity. However, fluorescent labels have fundamental limitations, including photo-bleaching, perturbation of biological structures, and inability to label small molecules. Te BSTP microscope pro- vides molecular information in phase microscopy without the need for labels. In one example, BSTP imaging showed that features of a living cell involved in CH2


asymmetrical stretch- ing (2930 cm−1 in CH3 stretching (2950 cm−1


) could be distinguished from features involved ). Live cell BSTP imaging can


be obtained at a 50 Hz frame rate with high spectral fidelity, sub-microsecond temporal resolution, and sub-micron spatial resolution. Applications envisioned include single-cell bio- chemistry, cell-drug interactions, and potentially the discovery of biomarkers that lead to diagnosis and treatment.


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