Nanocharacterization
plays a vital role in understanding the complex
nanoscale organization of cells and organelles. Understanding cellular
function requires high-resolution information about how the cellular
structures evolve over time. A number of techniques exist to resolve
static nanoscale structure of cells in great detail (super-resolution
optical microscopy, EM, AFM). However, time-resolved imaging techniques
tend to either have a lower resolution, are limited to small areas,
or cause damage to the cells, thereby preventing long-term time-lapse
studies. Scanning probe microscopy methods such as atomic force microscopy
(AFM) combine high-resolution imaging with the ability to image living
cells in physiological conditions. The mechanical contact between
the tip and the sample, however, deforms the cell surface, disturbs
the native state, and prohibits long-term time-lapse imaging. Here,
we develop a scanning ion conductance microscope (SICM) for high-speed
and long-term nanoscale imaging of eukaryotic cells. By utilizing
advances in nanopositioning, nanopore fabrication, microelectronics,
and controls engineering, we developed a microscopy method that can
resolve spatiotemporally diverse three-dimensional (3D) processes
on the cell membrane at sub-5-nm axial resolution. We tracked dynamic
changes in live cell morphology with nanometer details and temporal
ranges of subsecond to days, imaging diverse processes ranging from
endocytosis, micropinocytosis, and mitosis to bacterial infection
and cell differentiation in cancer cells. This technique enables a
detailed look at membrane events and may offer insights into cell–cell
interactions for infection, immunology, and cancer research.
In this paper, we present a pseudo-resistor-based transimpedance amplifier (TIA) whose transimpedance value is PVT-independent and continuously tuneable over a wide range. The nonlinearity of the pseudo-resistors is mitigated by connecting a large number of elements in series and the effect of process variations on the pseudo-resistor is canceled by a biasing network based on a pseudo current mirror. The design is also first order temperature compensated exploiting the PTAT behavior of the proposed pseudo-resistor and using a PTAT current reference for its biasing. The proposed architecture is verified using a prototype manufactured in a 0.18 µm CMOS SOI technology. In this prototype, the transimpedance can be adjusted between approximately 1 MΩ and 1 GΩ. The achievable bandwidth varies inversely proportional with the transimpedance value from around 7 kHz for a value of 1 GΩ up to an opamp-limited maximum of 2 MHz. In the white region, the input referred noise is equal to that of a TIA using an equivalent ohmic resistor. A minimum value of 5 fA/ √ Hz is achieved for a transimpedance of 1 GΩ. Over a temperature range from −40 • C to 125 • C, the transimpedance varies less than 10 % for 1 MΩ. The TIA occupies a chip area of 0.07 mm 2 . At room temperature, the power consumption is 9.5 mW from a single 1.8 V supply of which the pseudo-resistor consumes 0.2 mW.
A wavelength division multiplexing-based bidirectional optical transcutaneous telemetric data link for brain machine interfaces is reported. By converting the digitised electronic signals to a stream of infrared and visible optical pulses, the optical telemetry wirelessly transmits data between the implanted neural recorder/stimulator and the external control devices. A red visible vertical cavity surface emitting laser (VCSEL) with a peak wavelength of 680 nm is used in the downlink to transmit data from the external base unit to the implant. A near infrared VCSEL with a peak wavelength of 850 nm is utilised in the uplink for data transmission from the implants to the external device. An optical filter is applied to minimise the interference between the two channels. In-vitro experiments show that the uplink is capable of transmitting data at 100 Mbps through 2 mm of porcine skin while the downlink is simultaneously working at a rate of 1 Mbps. The power consumption of the implant part of the telemetry, including the transmitter for the uplink and the receiver for the downlink are 3.2 mW and 290 μW, corresponding to a transmission power efficiencies of 32 and 290 pJ/bit, respectively, which are among the best reported and unseen for bidirectional high-speed transcutaneous communication.
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