A compact and versatile microfluidic probe for local processing of tissue sections and biological specimens

Cors, Julien F.; Lovchik, Robert D.; Delamarche, Emmanuel; Kaigala, Govind V.

doi:10.1063/1.4866976

Cited by 18 publications

(15 citation statements)

References 36 publications

(40 reference statements)

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“…A key advantage of the MFP is its capacity to interact locally with a surface and to scan large areas rapidly. 36 Leveraging this capacity, we investigated the recirculation of a given volume of liquid on multiple positions on a substrate. Multizones deposition can be used for localized capture of antigens from a sample, and using a single microliter, recirculation allows multiple independent capture zones to be probed.…”

Section: Resultsmentioning

confidence: 99%

Convection-Enhanced Biopatterning with Recirculation of Hydrodynamically Confined Nanoliter Volumes of Reagents

et al. 2016

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We present a new methodology for efficient and high-quality patterning of biological reagents for surface-based biological assays. The method relies on hydrodynamically confined nanoliter volumes of reagents to interact with the substrate at the micrometer-length scale. We study the interplay between diffusion, advection, and surface chemistry and present the design of a noncontact scanning microfluidic device to efficiently present reagents on surfaces. By leveraging convective flows, recirculation, and mixing of a processing liquid, this device overcomes limitations of existing biopatterning approaches, such as passive diffusion of analytes, uncontrolled wetting, and drying artifacts. We demonstrate the deposition of analytes, showing a 2- to 5-fold increase in deposition rate together with a 10-fold reduction in analyte consumption while ensuring less than 6% variation in pattern homogeneity on a standard biological substrate. In addition, we demonstrate the recirculation of a processing liquid using a microfluidic probe (MFP) in the context of a surface assay for (i) probing 12 independent areas with a single microliter of processing liquid and (ii) processing a 2 mm2 surface to create 170 antibody spots of 50 × 100 μm2 area using 1.6 μL of liquid. We observe high pattern quality, conservative usage of reagents, micrometer precision of localization and convection-enhanced fast deposition. Such a device and method may facilitate quantitative biological assays and spur the development of the next generation of protein microarrays.

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Section: Resultsmentioning

confidence: 99%

Convection-Enhanced Biopatterning with Recirculation of Hydrodynamically Confined Nanoliter Volumes of Reagents

et al. 2016

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“…After bonding, the 4 channels (50 × 50 μm 2 section, spacing between apertures = 50 μm) were filled with wax and the bonded silicon/glass wafers were diced to form individual heads, which were polished. The heads were cleaned and used with an MFP platform 37 that sits on an inverted microscope (Nikon Eclipse). Images were acquired using an ORCA-Flash 4.0 camera (Hamamatsu) and a LED lamp (Sola, Lumencore).…”

Section: Methodsmentioning

confidence: 99%

Hierarchical Hydrodynamic Flow Confinement: Efficient Use and Retrieval of Chemicals for Microscale Chemistry on Surfaces

et al. 2014

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We devised, implemented, and tested a new concept for efficient local surface chemistry that we call hierarchical hydrodynamic flow confinement (hierarchical HFC). This concept leverages the hydrodynamic shaping of multiple layers of liquid to address challenges inherent to microscale surface chemistry, such as minimal dilution, economical consumption of reagent, and fast liquid switching. We illustrate two modes of hierarchical HFC, nested and pinched, by locally denaturing and recovering a 26 bp DNA with as little as 2% dilution and by efficiently patterning an antibody on a surface, with a 5 μm resolution and a 100-fold decrease of reagent consumption compared to microcontact printing. In addition, valveless switching between nanoliter volumes of liquids was achieved within 20 ms. We believe hierarchical HFC will have broad utility for chemistry on surfaces at the microscale.

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“…A microfluidic probe (MFP) has been proposed for improving the spatial resolution of humoral factor stimulation control within cell culture environments[10–14]. MFPs have two microchannels, which are located adjacently across a gap of the order of tens of microns.…”

Section: Introductionmentioning

confidence: 99%

Spatial Chemical Stimulation Control in Microenvironment by Microfluidic Probe Integrated Device for Cell-Based Assay

et al. 2016

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Cell—cell interactions play an important role in the development and function of multicellular organisms. To investigate these interactions in detail, it is necessary to evaluate the behavior of a cell population when the minimum number of cells in the population is stimulated by some chemical factors. We propose a microfluidic device integrated with microfluidic probe (MFP) functionality; this device is capable of imparting a chemical stimulus to cells within a microenvironment, for cell-based assays. The device contains MFP channels at the walls of the cell culture microchannels, and it can control a localized chemical stimulation area at the scale of a single cell to a few cells using MFP fluid control in a microspace. The results of a finite element method-based simulation indicated that it is possible to control the chemical stimulation area at the scale of a single cell to a few cells by optimizing the MFP channel apex width and the flow ratio. In addition, localized cell staining was demonstrated successfully using a spatial chemical stimulus. We confirmed the device functionality as a novel cell-based assay tool. We succeeded in performing localized cell collection using this method, which suggested that the single cell analysis of a cell monolayer that is subjected to a specific chemical stimulus is possible. The method proposed in this paper can contribute significantly to the fields of cell biology and drug development.

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A compact and versatile microfluidic probe for local processing of tissue sections and biological specimens

Cited by 18 publications

References 36 publications

Convection-Enhanced Biopatterning with Recirculation of Hydrodynamically Confined Nanoliter Volumes of Reagents

Convection-Enhanced Biopatterning with Recirculation of Hydrodynamically Confined Nanoliter Volumes of Reagents

Hierarchical Hydrodynamic Flow Confinement: Efficient Use and Retrieval of Chemicals for Microscale Chemistry on Surfaces

Spatial Chemical Stimulation Control in Microenvironment by Microfluidic Probe Integrated Device for Cell-Based Assay

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