Search

The advancement of sophisticated instrumentation in mass spectrometry has catalyzed an in-depth exploration of complex proteomes. This exploration necessitates a nuanced balance in experimental design, particularly between quantitative precision and the enumeration of analytes detected. In bottom-up proteomics, a key challenge is that oversampling of abundant proteins can adversely affect the identification of a diverse array of unique proteins. This issue is especially pronounced in samples with limited analytes, such as small tissue biopsies or single-cell samples. Methods such as depletion and fractionation are suboptimal to reduce oversampling in single cell samples, and other improvements on LC and mass spectrometry technologies and methods have been developed to address the trade-off between precision and enumeration. We demonstrate that by using a monosubstrate protease for proteomic analysis of single-cell equivalent digest samples, an improvement in quantitative accuracy can be achieved, while maintaining high proteome coverage established by trypsin. This improvement is particularly vital for the field of single-cell proteomics, where single-cell samples with limited number of protein copies, especially in the context of low-abundance proteins, can benefit from considering analyte complexity. Considerations about analyte complexity, alongside chromatographic complexity, integration with data acquisition methods, and other factors such as those involving enzyme kinetics, will be crucial in the design of future single-cell workflows.

Surface-initiated polymerization has been used to grow thick, uniform poly(methyl methacrylate) films on nanocantilever sensors. Cantilevers with these coatings yielded significantly greater sensitivity relative to bare devices as well as relative to devices that had been coated with drop-cast polymer films. The devices with surface-initiated polymer films also demonstrated high selectivity toward polar analytes. Surface-initiated polymerization can therefore provide a straightforward, reproducible method for large-scale functionalization of nanosensors.

Neuroscience is at a crossroads. Great effort is being invested into deciphering specific neural interactions and circuits. At the same time, there exist few general theories or principles that explain brain function. We attribute this disparity, in part, to limitations in current methodologies. Traditional neurophysiological approaches record the activities of one neuron or a few neurons at a time. Neurochemical approaches focus on single neurotransmitters. Yet, there is an increasing realization that neural circuits operate at emergent levels, where the interactions between hundreds or thousands of neurons, utilizing multiple chemical transmitters, generate functional states. Brains function at the nanoscale, so tools to study brains must ultimately operate at this scale, as well. Nanoscience and nanotechnology are poised to provide a rich toolkit of novel methods to explore brain function by enabling simultaneous measurement and manipulation of activity of thousands or even millions of neurons. We and others refer to this goal as the Brain Activity Mapping Project. In this Nano Focus, we discuss how recent developments in nanoscale analysis tools and in the design and synthesis of nanomaterials have generated optical, electrical, and chemical methods that can readily be adapted for use in neuroscience. These approaches represent exciting areas of technical development and research. Moreover, unique opportunities exist for nanoscientists, nanotechnologists, and other physical scientists and engineers to contribute to tackling the challenging problems involved in understanding the fundamentals of brain function.

We describe and demonstrate a new oscillator topology, the parametric feedback oscillator (PFO). The PFO paradigm is applicable to a wide variety of nanoscale devices and opens the possibility of new classes of oscillators employing innovative frequency-determining elements, such as nanoelectromechanical systems (NEMS), facilitating integration with circuitry and system-size reduction. We show that the PFO topology can also improve nanoscale oscillator performance by circumventing detrimental effects that are otherwise imposed by the strong device nonlinearity in this size regime.

We demonstrate the parametric amplification and noise squeezing of nanomechanical motion utilizing dispersive coupling to a Cooper-pair box qubit. By modulating the qubit bias and resulting mechanical resonance shift, we achieve gain of 30 dB and noise squeezing of 4 dB. This qubit-mediated effect is 3000 times more effective than that resulting from the weak nonlinearity of capacitance to a nearby electrode. This technique may be used to prepare nanomechanical squeezed states.

Nanoscale integrated circuits and sensors will require methods for unobtrusive interconnection with the macroscopic world to fully realize their potential. We report on a nanoelectromechanical system that may present a solution to the wiring problem by enabling information from multisite sensors to be multiplexed onto a single output line. The basis for this method is a mechanical Fourier transform mediated by piezoelectrically coupled nanoscale resonators. Our technique allows sensitive, linear, and real-time measurement of electrical potentials from conceivably any voltage-sensitive device. With this method, we demonstrate the direct transduction of neuronal action potentials from an extracellular microelectrode. This approach to wiring nanoscale devices could lead to minimally invasive implantable sensors with thousands of channels for in vivo neuronal recording, medical diagnostics, and electrochemical sensing.

We have developed an ultrasensitive nanoscale calorimeter that enables heat capacity measurements upon minute, externally affixed (phonon-coupled) samples at low temperatures. For a 5 s measurement at 2 K, we demonstrate an unprecedented resolution of DeltaC approximately 0.5 aJ/K ( approximately 36 000 k(B)). This sensitivity is sufficient to enable heat capacity measurements upon zeptomole-scale samples or upon adsorbates with sub-monolayer coverage across the minute cross sections of these devices. We describe the fabrication and operation of these devices and demonstrate their sensitivity by measuring an adsorbed (4)He film with optimum resolution of approximately 3 x 10(-5) monolayers upon an active surface area of only approximately 1.2 x 10(-9) m(2).