This thesis explores transport phenomena in nanochannels on a chip. Fundamental nanofluidic ionic studies form the basis for novel separation and preconcentration applications for proteomic purposes. The measurements were performed with 50-nm-high 1D nanochannels, which are easily accessible from both sides by two microchannels. Nanometer characteristic apertures were manufactured in the bonded structure of Pyrex-amorphous silicon – Pyrex, in which the thickness of the amorphous silicon layer serves as a spacer to define the height of the nanochannels. The geometry of the nanometer-sized apertures is well defined, which simplifies the modeling of the transport across them. Compared to biological pores, the present nanochannels in Pyrex offer increased stability. Fundamental characteristics of nanometer-sized apertures were obtained by impedance spectroscopy measurements of the nanochannel at different ionic strengths and pH values. A conductance plateau (on a log-log scale) was modeled and measured, establishing due to the dominance of the surface charge density in the nanochannels, which induces an excess of mobile counterions to maintain electroneutrality. The nanochannel conductance can be regulated at low ionic strengths by pH adjustment, and by an external voltage applied on the chip to change the zeta potential. This field-effect allows the regulation of ionic flow which can be exploited for the fabrication of nanofluidic devices. Fluorescence measurements confirm that 50-nm-high nanochannels show an exclusion of co-ions and an enrichment of counterions at low ionic strengths. This permselectivity is related to the increasing thickness of the electrical double layer (EDL) with decreasing salt concentrations, which results in an EDL overlap in an aperture if the height of the nanochannel and the thickness of the EDL are comparable in size. The diffusive transport of charged species and therefore the exclusion-enrichment effect was described with a simple model based on the Poisson-Boltzmann equation. The negatively charged Pyrex surface of the nanometer characteristic apertures can be inversed with chemical surface pretreatments, resulting in an exclusion of cations and an enrichment of anions. When a pressure gradient is applied across the nanochannels, charged molecules are electrostatically rejected at the entrance of the nanometer-sized apertures, which can be used for separation processes. Proteomic applications are presented such as the separation and preconcentration of proteins. The diffusion of Lectin proteins with different isoelectric points and very similar compositions were controlled by regulating the pH value of the buffer. When the proteins are neutral at their pI value, the diffusion coefficient is maximal because the biomolecules does not interact electrostatically with the charged surfaces of the nanochannel. This led to a fast separation of three Lectin proteins across the nanochannel. The pI values measured in this experiment are slightly shifted compared to the values obtained with isoelectric focusing because of reversible adsorption of proteins on the walls which affects the pH value in the nanochannel. An important application in the proteomic field is the preconcentration of biomolecules. By applying an electric field across the nanochannel, anionic and cationic analytes were preconcentrated on the cathodic side of the nanometer-sized aperture whereas on the anodic side depletion of ions was observed. This is due to concentration polarization, a complex of effects related to the formation of ionic concentration gradients in the electrolyte solution adjacent to an ion-selective interface. It was measured that the preconcentration factor increased with the net charge of the molecule, leading to a preconcentration factor of > 600 for rGFP proteins in 9 minutes. Such preconcentrations are important in micro total analysis systems to achieve increased detection signals of analytes contained in dilute solutions. Compared to cylindrical pores, our fabrication process allows the realization of nanochannels on a chip in which the exclusion-enrichment effect and a big flux across the nanometer-sized aperture can be achieved, showing the interest for possible micro total analysis system applications. The described exclusion-enrichment effect as well as concentration polarization play an important role in transport phenomena in nanofluidics. The appendix includes preliminary investigations in DNA molecule separation and fluorescence correlation spectroscopy measurements, which allows investigating the behavior of molecules in the nanochannel itself.

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Transport phenomena in nanofluidics

Recent development in 2D materials beyond graphene

Health, infrastructure, and environmental monitoring as well as networking and defense technologies are only some of the potential areas of application of micro-/nanosystems (MNSs). It is highly desirable that these MNSs operate without an external electricity source and instead draw the energy they require from the environment in which they are used. This Review covers various approaches for energy harvesting to meet the future demand for self-powered MNSs.

Nanotechnology-Enabled Energy Harvesting for Self-Powered Micro-/Nanosystems

Mechanical interactions are fundamental to biology. Mechanical forces of chemical origin determine motility and adhesion on the cellular scale, and govern transport and affinity on the molecular scale. Biological sensing in the mechanical domain provides unique opportunities to measure forces, displacements and mass changes from cellular and subcellular processes. Nanomechanical systems are particularly well matched in size with molecular interactions, and provide a basis for biological probes with single-molecule sensitivity. Here we review micro- and nanoscale biosensors, with a particular focus on fast mechanical biosensing in fluid by mass- and force-based methods, and the challenges presented by non-specific interactions. We explain the general issues that will be critical to the success of any type of next-generation mechanical biosensor, such as the need to improve intrinsic device performance, fabrication reproducibility and system integration. We also discuss the need for a greater understanding of analyte–sensor interactions on the nanoscale and of stochastic processes in the sensing environment.

Comparative advantages of mechanical biosensors

The past decade has seen researchers develop and apply novel technologies for biomolecular detection, at times approaching hard limits imposed by physics and chemistry. In nearly all sensors, the transport of target molecules to the sensor can play as critical a role as the chemical reaction itself in governing binding kinetics, and ultimately performance. Yet rarely does an analysis of the interplay between diffusion, convection and reaction motivate experimental design or interpretation. Here we develop a physically intuitive and practical understanding of analyte transport for researchers who develop and employ biosensors based on surface capture. We explore the qualitatively distinct behaviors that result, develop rules of thumb to quickly determine how a given system will behave, and derive order-of-magnitude estimates for fundamental quantities of interest, such as fluxes, collection rates and equilibration times. We pay particular attention to collection limits for micro- and nanoscale sensors, and highlight unexplained discrepancies between reported values and theoretical limits.

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Making it stick: convection, reaction and diffusion in surface-based biosensors.

Semiconducting nanowires have the potential to act as highly sensitive sensors for the detection of pathogenic microorganisms, without the need for a label on the pathogen. Practical miniature sensors would have applications in diagnostics, homeland security and basic research. Current technologies have not been widely adopted for various reasons, including the difficulty of integrating nanoscale devices into practical sensors. Now a team spanning five departments at Yale has developed a new approach to the problem. In a state-of-the-art (CMOS-compatible) system they create miniature, ultra-sensitive sensors that can detect specific unlabelled antibodies at concentrations below 100 femtomolar and are able to monitor the cellular immune response in 'real-time'. A new approach that uses complementary metal oxide semiconductor field effect transistor compatible technology is reported, and demonstrates the specific label-free detection of below 100 femtomolar concentrations of antibodies as well as real-time monitoring of the cellular immune response. Semiconducting nanowires have the potential to function as highly sensitive and selective sensors for the label-free detection of low concentrations of pathogenic microorganisms1,2,3,4,5,6,7,8,9,10. Successful solution-phase nanowire sensing has been demonstrated for ions3, small molecules4, proteins5,6, DNA7 and viruses8; however, ‘bottom-up’ nanowires (or similarly configured carbon nanotubes11) used for these demonstrations require hybrid fabrication schemes12,13, which result in severe integration issues that have hindered widespread application. Alternative ‘top-down’ fabrication methods of nanowire-like devices9,10,14,15,16,17 produce disappointing performance because of process-induced material and device degradation. Here we report an approach that uses complementary metal oxide semiconductor (CMOS) field effect transistor compatible technology and hence demonstrate the specific label-free detection of below 100 femtomolar concentrations of antibodies as well as real-time monitoring of the cellular immune response. This approach eliminates the need for hybrid methods and enables system-scale integration of these sensors with signal processing and information systems. Additionally, the ability to monitor antibody binding and sense the cellular immune response in real time with readily available technology should facilitate widespread diagnostic applications.

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Label-free immunodetection with CMOS-compatible semiconducting nanowires

The design, synthesis, and structural analysis of a new foldamer that mimics an extended β-sheet are presented. The nonpeptidic mimetic is based on a series of 2,2-disubstituted-indolin-3-one group...

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Alkyne-linked 2,2-disubstituted-indolin-3-one oligomers as extended β-strand mimetics

The systems and methods described herein include a sensor for suitable for sensing chemical and biological substances. The sensor comprises a semiconductor layer formed in or on a substrate and a channel having nano-scale dimensions formed in the semiconductor layer, where the structure creates an electrically conducting pathway between a first contact and a second contact on the semiconductor layer. In certain preferred embodiments, the nano-scale channel has a trapezoidal cross-section with an effective width and exposed lateral faces, where the effective width is selected to have same order of magnitude as a Debye length (LD) of the semiconductor material of which the semiconductor layer is formed.

Pauline N. Wyrembak

Papers

Label-free immunodetection with CMOS-compatible semiconducting nanowires

Alkyne-linked 2,2-disubstituted-indolin-3-one oligomers as extended β-strand mimetics

Systems and Methods for CMOS-Compatible Silicon Nano-Wire Sensors with Biochemical and Cellular Interfaces

Inhibition of Protein-Protein Interactions by Peptide Mimics