Integration of atomic force microscopy and a microfluidic liquid cell for aqueous imaging and force spectroscopy

Abstract

We have designed and built a microfluidic liquid cell capable of high-resolution atomic force microscope (AFM) imaging and force spectroscopy. The liquid cell was assembled from three molded poly(dimethylsiloxane) (PDMS) pieces and integrated with commercially purchased probes. The AFM probe was embedded within the assembly such that the cantilever and tip protrude into the microfluidic channel. This channel is defined by the PDMS assembly on the top, a PDMS gasket on all four sides, and the sample substrate on the bottom, forming a liquid-tight seal. Our design features a low volume fluidic channel on the order of 50 nl, which is a reduction of over 3-5 orders of magnitude compared to several commercial liquid cells. This device facilitates testing at high shear rates and laminar flow conditions coupled with full AFM functionality in microfluidic aqueous environments, including execution of both force displacement curves and high resolution imaging.

Characterization of Embryonic Stem (ES) Neuronal Differentiation Combining Atomic Force, Confocal and DIC Microscopy Imaging

“…Integrated AFM and CLSM instrument has been developed and it offers the advantage of parallel analysis of the same sample with nanometer-scale spatial resolution, frame/second temporal resolution, and chemical identification through fluorescence detection can be done simultaneously for live cells (Doak et al, 2008;Park et al, 2010). In addition to optical microscopy, AFM can be combined with other instruments and techniques, such as microfluidic liquid cell (Schoenwald et al, 2010), patch-clamp (Pamir et al, 2008) or ultramicrotome (Efimov et al, 2007) providing a novel insights to further understanding of cellular structure-function relationships getting down to the scale of single molecule. Although there are several studies where AFM is combined with confocal microscope (Doak et al, 2008;Moreno Flores & Toca-Herrera., 2009;Kassies et al, 2005;Owen et al, 2006;Park et al, 2010), our method is useful in cases where combined fluorescence (confocal) and atomic force microscope is not available.…”

3D‐Printed Scanning‐Probe Microscopes with Integrated Optical Actuation and Read‐Out

“…Operation of conventional AFM assemblies in liquids typically requires mechanical realignment of the laser beam to compensate optical refraction at the liquid surface. Offering compact footprint, robustness, simple alignment, and remote operation through optical waveguides, we expect that 3D-printed SPM engines will open new perspectives for in vitro and in vivo imaging, [7][8][9] applications in lab-on-chip or microfluidic devices, [33] or endoscopic AFM systems.…”

“…As a second example, we show the capability of our AFM engines to switch between measurements in air and in liquids, which is helpful, e.g., for imaging of biological samples, [7][8][9] process monitoring in chemical reactors, or for the integration of AFM engines into microfluidic systems. [33] The associated structure (Figure 3a) is again printed onto the facets of an SMF array, which enables remote operation over extended distances without any mechanical alignment of the AFM components. The cantilever is now designed as a massive structure with a thickness of 21 µm, leading to a dynamic behavior which is rather insensitive to the surrounding medium.…”

High Force Sensitivity Composite Nanofluidic AFM Cantilever

“…1, top. Furthermore, an integrated microfluidic liquid cell enables high shear fluid flow across the cantilever, introducing an additional parameter to the multimodal capability of the described system [13].…”