scholarly journals Scalable integration of nano-, and microfluidics with hybrid two-photon lithography

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Oliver Vanderpoorten ◽  
Quentin Peter ◽  
Pavan K. Challa ◽  
Ulrich F. Keyser ◽  
Jeremy Baumberg ◽  
...  

Abstract Nanofluidic devices have great potential for applications in areas ranging from renewable energy to human health. A crucial requirement for the successful operation of nanofluidic devices is the ability to interface them in a scalable manner with the outside world. Here, we demonstrate a hybrid two photon nanolithography approach interfaced with conventional mask whole-wafer UV-photolithography to generate master wafers for the fabrication of integrated micro and nanofluidic devices. Using this approach we demonstrate the fabrication of molds from SU-8 photoresist with nanofluidic features down to 230 nm lateral width and channel heights from micron to sub-100 nm. Scanning electron microscopy and atomic force microscopy were used to characterize the printing capabilities of the system and show the integration of nanofluidic channels into an existing microfluidic chip design. The functionality of the devices was demonstrated through super-resolution microscopy, allowing the observation of features below the diffraction limit of light produced using our approach. Single molecule localization of diffusing dye molecules verified the successful imprint of nanochannels and the spatial confinement of molecules to 200 nm across the nanochannel molded from the master wafer. This approach integrates readily with current microfluidic fabrication methods and allows the combination of microfluidic devices with locally two-photon-written nano-sized functionalities, enabling rapid nanofluidic device fabrication and enhancement of existing microfluidic device architectures with nanofluidic features.

2012 ◽  
Vol 20 (5) ◽  
pp. 24-29 ◽  
Author(s):  
Adam R. Hall

There are relatively few technologies for measurement at the single-molecule scale. Fluorescent imaging, for example, can be used to directly visualize molecules and their interactions, but diffraction limitations and labeling requirements may push the system from its native state. Although recent advances in super-resolution imaging have been able to break this resolution barrier, important challenges remain. Atomic force microscopy (AFM) is capable of imaging molecules at high resolution and at high speed. However, AFM imaging is a surface technique, requiring sample preparation and some immobilization. Other technologies such as optical tweezers and magnetic tweezers are capable of molecular manipulation and spectroscopy to great effect but require a significant apparatus and have limited inherent analytical capabilities.


2016 ◽  
Vol 4 (4) ◽  
Author(s):  
Rapeepan Promyoo ◽  
Hazim El-Mounayri ◽  
Mangilal Agarwal ◽  
Varun Kumar Karingula ◽  
Kody Varahramyan

Presently, nanomanufacturing capabilities limit the commercialization of a broader range of nanoscale structures with higher complexity, greater precision and accuracy, and a substantially improved performance. Atomic force microscopy (AFM)-based nanomachining is a promising technique to address current limitations and is considered a potential manufacturing (MFG) tool for operations such as machining, patterning, and assembling with in situ metrology and visualization. Most existing techniques for fabrication of nanofluidic channels involve the use of electron-beam lithography, which is a very expensive process that requires a lengthy calibration procedure. In this work, atomic force microscopy (AFM) is employed in the fabrication of nanofluidic channels for medical applications. Channels with various depths and widths are fabricated using AFM indentation and scratching. A nanoscale channel is mainly used in the study of the molecular behavior at single molecule level. The resulting device can be used for detecting, analyzing and separating biomolecules, DNA stretching, and separation of elite group of lysosome and other viruses. The nanochannels are integrated between microchannels and act as filters to separate biomolecules. Sharply developed vertical microchannels are produced from deep reaction ion etching. Poly-dimethylsiloxane (PDMS) bonding is performed to close the top surface of the silicon device. An experimental setup is used for testing by flowing fluid through the channels. A cost evaluation shows 47.7% manufacturing-time and 60.6% manufacturing-cost savings, compared to more traditional processes.


2013 ◽  
pp. 102-112
Author(s):  
Memed Duman ◽  
Andreas Ebner ◽  
Christian Rankl ◽  
Jilin Tang ◽  
Lilia A. Chtcheglova ◽  
...  

Materials ◽  
2021 ◽  
Vol 14 (3) ◽  
pp. 687
Author(s):  
Amna Abdalla Mohammed Khalid ◽  
Pietro Parisse ◽  
Barbara Medagli ◽  
Silvia Onesti ◽  
Loredana Casalis

The MCM (minichromosome maintenance) protein complex forms an hexameric ring and has a key role in the replication machinery of Eukaryotes and Archaea, where it functions as the replicative helicase opening up the DNA double helix ahead of the polymerases. Here, we present a study of the interaction between DNA and the archaeal MCM complex from Methanothermobacter thermautotrophicus by means of atomic force microscopy (AFM) single molecule imaging. We first optimized the protocol (surface treatment and buffer conditions) to obtain AFM images of surface-equilibrated DNA molecules before and after the interaction with the protein complex. We discriminated between two modes of interaction, one in which the protein induces a sharp bend in the DNA, and one where there is no bending. We found that the presence of the MCM complex also affects the DNA contour length. A possible interpretation of the observed behavior is that in one case the hexameric ring encircles the dsDNA, while in the other the nucleic acid wraps on the outside of the ring, undergoing a change of direction. We confirmed this topographical assignment by testing two mutants, one affecting the N-terminal β-hairpins projecting towards the central channel, and thus preventing DNA loading, the other lacking an external subdomain and thus preventing wrapping. The statistical analysis of the distribution of the protein complexes between the two modes, together with the dissection of the changes of DNA contour length and binding angle upon interaction, for the wild type and the two mutants, is consistent with the hypothesis. We discuss the results in view of the various modes of nucleic acid interactions that have been proposed for both archaeal and eukaryotic MCM complexes.


Biochemistry ◽  
2007 ◽  
Vol 46 (10) ◽  
pp. 2797-2804 ◽  
Author(s):  
Theeraporn Puntheeranurak ◽  
Barbara Wimmer ◽  
Francisco Castaneda ◽  
Hermann J. Gruber ◽  
Peter Hinterdorfer ◽  
...  

2010 ◽  
Vol 63 (4) ◽  
pp. 624
Author(s):  
Michael J. Serpe ◽  
Jason R. Whitehead ◽  
Stephen L. Craig

Single molecule atomic force microscopy (AFM) studies of oligonucleotide-based supramolecular polymers on surfaces are used to examine the molecular weight distribution of the polymers formed between a functionalized surface and an AFM tip as a function of monomer concentration. For the concentrations examined here, excellent agreement with a multi-stage open association model of polymerization is obtained, without the need to invoke additional contributions from secondary steric interactions at the surface.


Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1756
Author(s):  
Xuchang Su ◽  
Zhi He ◽  
Lijun Meng ◽  
Hong Liang ◽  
Ruhong Zhou

Single-molecule techniques such as electron tunneling and atomic force microscopy have attracted growing interests in protein sequencing. For these methods, it is critical to refine and stabilize the protein sample to a “suitable mode” before applying a high-fidelity measurement. Here, we show that a planar heterostructure comprising boronic graphene (BC3) and nitrogenized graphene (C3N) sandwiched stripe (BC3/C3N/BC3) is capable of the effective stretching and confinement of three types of intrinsically disordered proteins (IDPs), including amyloid-β (1–42), polyglutamine (Q42), and α-Synuclein (61–95). Our molecular dynamics simulations demonstrate that the protein molecules interact more strongly with the C3N stripe than the BC3 one, which leads to their capture, elongation, and confinement along the center C3N stripe of the heterostructure. The conformational fluctuations of IDPs are substantially reduced after being stretched. This design may serve as a platform for single-molecule protein analysis with reduced thermal noise.


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