Nomarski serial time-encoded amplified microscopy for high-speed contrast-enhanced imaging of transparent media

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Abstract

High-speed high-contrast imaging modalities that enable image acquisition of transparent media without the need for chemical staining are essential tools for a broad range of applications; from semiconductor process monitoring to blood screening. Here we introduce a method for contrast-enhanced imaging of unstained transparent objects that is capable of high-throughput imaging. This method combines the Nomarski phase contrast capability with the ultrahigh frame rate and shutter speed of serial time-encoded amplified microscopy. As a proof of concept, we show imaging of a transparent test structure and white blood cells in flow at a shutter speed of 33 ps and a frame rate of 36.1 MHz using a single-pixel photo-detector. This method is expected to be a valuable tool for high-throughput screening of unstained cells.

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Continuous inertial focusing, ordering, and separation of particles in microchannels.

Dino Di Carlo, Daniel Irimia, Ronald Tompkins … (2007)

Under laminar flow conditions, when no external forces are applied, particles are generally thought to follow fluid streamlines. Contrary to this perspective, we observe that flowing particles migrate across streamlines in a continuous, predictable, and accurate manner in microchannels experiencing laminar flows. The migration is attributed to lift forces on particles that are observed when inertial aspects of the flow become significant. We identified symmetric and asymmetric channel geometries that provide additional inertial forces that bias particular equilibrium positions to create continuous streams of ordered particles precisely positioned in three spatial dimensions. We were able to order particles laterally, within the transverse plane of the channel, with >80-nm accuracy, and longitudinally, in regular chains along the direction of flow. A fourth dimension of rotational alignment was observed for discoidal red blood cells. Unexpectedly, ordering appears to be independent of particle buoyant direction, suggesting only minor centrifugal contributions. Theoretical analysis indicates the physical principles are operational over a range of channel and particle length scales. The ability to differentially order particles of different sizes, continuously, at high rates, and without external forces in microchannels is expected to have a broad range of applications in continuous bioparticle separation, high-throughput cytometry, and large-scale filtration systems.

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Inertial microfluidics.

Dino Di Carlo (2009)

Despite the common wisdom that inertia does not contribute to microfluidic phenomena, recent work has shown a variety of useful effects that depend on fluid inertia for applications in enhanced mixing, particle separation, and bioparticle focusing. Due to the robust, fault-tolerant physical effects employed and high rates of operation, inertial microfluidic systems are poised to have a critical impact on high-throughput separation applications in environmental cleanup and physiological fluids processing, as well as bioparticle focusing applications in clinical diagnostics. In this review I will discuss the recent accelerated progress in developing prototype inertial microfluidic systems for a variety of applications and attempt to clarify the fundamental fluid dynamic effects that are being exploited. Finally, since this a nascent area of research, I will suggest some future promising directions exploiting fluid inertia on the microscale.

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Light microscopy techniques for live cell imaging.

David J. Stephens, Victoria Allan (2003)

Since the earliest examination of cellular structures, biologists have been fascinated by observing cells using light microscopy. The advent of fluorescent labeling technologies plus the plethora of sophisticated light microscope techniques now available make studying dynamic processes in living cells almost commonplace. For anyone new to this area, however, it can be daunting to decide which techniques or equipment to try. Here, we aim to give a brief overview of the main approaches to live cell imaging, with some mention of their pros and cons.

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Author and article information

Journal

Journal ID (nlm-ta): Biomed Opt Express

Journal ID (publisher-id): BOE

Title: Biomedical Optics Express

Publisher: Optical Society of America

ISSN (Electronic): 2156-7085

Publication date (Electronic): 29 November 2011

Publication date Collection: 01 December 2011

Publication date PMC-release: 29 November 2011

Volume: 2

Issue: 12

Pages: 3387-3392

Affiliations

[1 ]Department of Electrical Engineering, University of California, 420 Westwood Plaza, Los Angeles, CA 90095, USA

[2 ]California NanoSystems Institute, University of California, 570 Westwood Plaza, Los Angeles, CA 90095, USA

[3 ]Department of Bioengineering, University of California, 420 Westwood Plaza, Los Angeles, CA 90095, USA

[4 ]Department of Surgery, David Geffen School of Medicine, University of California, 20 Medical Plaza, Los Angeles, CA 90095, USA

Author notes

[* ] ali.fard@ 123456ucla.edu

Article

Publisher ID: 156867

DOI: 10.1364/BOE.2.003387

PMC ID: 3233256

PubMed ID: 22162827

SO-VID: ae18acfc-69e5-4d8e-80d8-8f7281ad98b9

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 Unported License, which permits download and redistribution, provided that the original work is properly cited. This license restricts the article from being modified or used commercially.

History

Date received : 21 October 2011

Date revision received : 18 November 2011

Date accepted : 22 November 2011

Funding

Funded by: United States Army and Defense Advanced Research Projects Agency

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ScienceOpen disciplines: Vision sciences

Keywords: (110.0180) microscopy,(180.3170) interference microscopy,(320.7160) ultrafast technology

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ScienceOpen disciplines: Vision sciences

Keywords: (110.0180) microscopy, (180.3170) interference microscopy, (320.7160) ultrafast technology

Nomarski serial time-encoded amplified microscopy for high-speed contrast-enhanced imaging of transparent media

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Abstract

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Karger: Ophthalmology

Most cited references 19

Continuous inertial focusing, ordering, and separation of particles in microchannels.

Inertial microfluidics.

Light microscopy techniques for live cell imaging.

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