Summary Paragraph Sensory, motor, and cognitive operations involve the coordinated action of large neuronal populations across multiple brain regions in both superficial and deep structures1,2. Existing extracellular probes record neural activity with excellent spatial and temporal (sub-millisecond) resolution but from only a few dozen neurons per shank. Optical Ca2+ imaging3–5 offers more coverage but lacks the temporal resolution to reliably distinguish individual spikes and does not measure local field potentials. To date, no technology compatible with unrestrained animals has combined high spatiotemporal resolution with large volume coverage. To satisfy this need, we designed, fabricated, and tested a new silicon probe called Neuropixels. Each probe has 384 recording channels that can programmably address 960 CMOS processing-compatible low-impedance TiN6 sites that tile a single 10 mm long, 70x20 µm cross section shank. The 6x9 mm probe base is fabricated with the shank on a single chip. Voltage signals are filtered, amplified, multiplexed, and digitized on the base, allowing noise-free digital data transmission directly from the probe. The combination of dense recording sites and high channel count yielded well-isolated spiking activity from hundreds of neurons per probe implanted in mice and rats. Using two probes, more than 700 well-isolated single neurons were simultaneously recorded from five brain structures in an awake mouse. The fully integrated functionality and small size of Neuropixels probes allowed recording large populations of neurons from multiple brain structures in freely moving animals. This combination of high-performance electrode technology and scalable chip fabrication methods opens the path to record brain-wide neural activity during behavior.

We present a systematic study of the effect of size and shape on the spectral response of individual silver nanoparticles. An experimental method has been developed that begins with the detection and characterization of isolated nanoparticles in the optical far field. The plasmon resonance optical spectrum of many individual nanoparticles are then correlated to their size and shape using high-resolution transmission electron microscopy. We find that specific geometrical shapes give distinct spectral responses. In addition, inducing subtle changes in the particles’ morphology by heating causes a shift in the individual particle spectrum and provides a simple means of tuning the spectral response to a desired optical wavelength. Improved colloidal preparation methods could potentially lead to homogeneous populations of identical particle shapes and colors. These multicolor colloids could be used as biological labels, surface enhanced Raman scattering substrates, or near field optical microscopy sources covering the full range of wavelengths in the visible spectrum.

Fabrication and readout of devices with progressively smaller size, ultimately down to the molecular scale, is critical for the development of very-high-frequency nanoelectromechanical systems (NEMS). Nanomaterials, such as carbon nanotubes or nanowires, offer immense prospects as active elements for these applications. We report the fabrication and measurement of a platinum nanowire resonator, 43 nm in diameter and 1.3 μm in length. This device, among the smallest NEMS reported, has a fundamental vibration frequency of 105.3 MHz, with a quality factor of 8500 at 4 K. Its resonant motion is transduced by a technique that is well suited to ultrasmall mechanical structures.

Recordings of large neuronal ensembles and neural stimulation of high spatial and temporal precision are important requisites for studying the real-time dynamics of neural networks. Multiple-shank silicon probes enable large-scale monitoring of individual neurons. Optical stimulation of genetically targeted neurons expressing light-sensitive channels or other fast (milliseconds) actuators offers the means for controlled perturbation of local circuits. Here we describe a method to equip the shanks of silicon probes with micron-scale light guides for allowing the simultaneous use of the two approaches. We then show illustrative examples of how these compact hybrid electrodes can be used in probing local circuits in behaving rats and mice. A key advantage of these devices is the enhanced spatial precision of stimulation that is achieved by delivering light close to the recording sites of the probe. When paired with the expression of light-sensitive actuators within genetically specified neuronal populations, these devices allow the relatively straightforward and interpretable manipulation of network activity.

Success in the projects aimed at providing an advanced understanding of the brain is directly predicated on making critical advances in nanotechnology. This Perspective addresses the unique interface of neuroscience and nanomaterials by considering the foundational problem of sensing neuron membrane voltage and offers a potential solution that may be facilitated by a prototypical nanomaterial. Despite substantial improvements, the visualization of instantaneous voltage changes within individual neurons, whether in cell culture or in vivo, at both the single-cell and network level at high speed remains complex and problematic. The unique properties of semiconductor quantum dots (QDs) have made them powerful fluorophores for bioimaging. What is not widely appreciated, however, is that QD photoluminescence is exquisitely sensitive to proximal electric fields. This property should be suitable for sensing voltage changes that occur in the active neuronal membrane. Here, we examine the potential role of QDs in addressing the important challenge of real-time optical voltage imaging.

We present a method of fabricating single crystal silver nanowires based on the electroless deposition of silver into the pores of the polycarbonate membranes by the metal amplification process. A gold film on one side of the nanoporous membrane is used as the initiation layer for the silver crystal growth, while the pores of the membrane are used for guiding the growth of the silver crystal into a cylindrical nanostructure. Optical microscopy and spectroscopy of individual nanowires, transmission electron microscopy (TEM), and TEM diffraction crystallography were used to characterize the silver nanostructures. The metal amplification technique presents an electroless, simple, and inexpensive solution to the challenge of fabricating silver nanowires for electronic, optical, and biological applications.

Targeting visually-identified neurons for electrophysiological recording is a fundamental neuroscience technique; however, its potential is hampered by poor visualization of pipette tips in deep brain tissue. We describe a technique whereby quantum dots coat glass pipettes providing strong two-photon contrast at deeper penetration depths than current methods. We demonstrate utility in targeted patch-clamp recording experiments and single cell electroporation from identified rat and mouse neurons in vitro and in vivo.

Articles you may be interested inFiber-optic rotation of micro-scale structures enabled microfluidic actuation and self-scanning two-photon excitation Appl.An electromagnetic micromotor has been developed that combines microcoils and magnetic microtips as stator elements and individual permanent magnet single domain particles as rotors. The three-phase stator microcoils ͑with poles separated by 100 m͒ are positioned outside the fluid, and the rotor ͑a 40 m long, 1 m diam permanent magnet͒ spins in aqueous solution 50 m from the stator. The small size and essentially disposable rotors make the magnetic micromotor attractive for use in microfluidics systems for various physical, chemical, and biological applications.