Miniaturized bioelectronic probes stand to transform biology and medicine by allowing measurement of intracellular components in vivo. Recently, scientists at Harvard University and Peking University designed, fabricated and demonstrated bioelectronic probes as small as 5 nanometers using a unique three-dimension nanowire-nanotube heterostructure. (A heterostructure combines multiple heterojunctions – interfaces between two layers or regions of dissimilar crystalline semiconductor – in a single device.) Through experimental measurements and numerical simulations, the researchers showed that these devices have sufficient time resolution to record the fastest electrical signals in neurons and other cells, with integration into larger chip arrays potentially providing ultra-high-resolution mapping of activity in neural networks and other biocellular systems.
Prof. Xiaojie Duan discussed the paper that she, Graduate Researcher Tian-Ming Fu, Prof. Charles M. Lieber and their co-authors published in Proceedings of the National Academy of Sciences. She first points out that nanotube probes and their heterojunction with silicon nanowire field-effect transistors (SiNW FETs) become mechanically less stable as diameter is reduced. "When the nanotube gets smaller and smaller," Duan tells Phys.org, "it gets easier to break the nanotube at the junction area with the SiNW. In the application of using the probe for intracellular bioelectronic detection, there will be various forces, such as the capillary force from the liquid, as well as interaction between the probe and the cell membrane. These forces may break the probe if we have a weak junction between it and the SiNW."
Another issue is that electrical sensitivity is also reduced as nanotube diameter decreases, because the nanotube inner diameter (ID) defines the effective device gate area. "In the recording of intracellular transmembrane potential using our probe," Duan explains, "cytosol fills the nanotube and acts as the gate electrode for the underlying SiNW FET." Cytosol (also termed intracellular fluid or cytoplasmic matrix) is the liquid found inside cells, excluding organelles and other cytoplasmic components. "The cytosol potential change modulates the carrier density of the SiNW FET, thereby changing its conductance," Duan continues. "This is how our probe works for bioelectronics recording." The contact area between the cytosol and the SiNW – defined by the inner diameter of the nanotube – determines conductance modulation effectiveness. In other words, if the nanotube inner diameter is too small, the SiNW FET gate area will be too small as well.
Moving forward, says Duan, the researchers' are planning to scale up their work to integrate the probes into high-density, large-scale array for large-scale mapping of neural activities; use the probes to record neural signals from small subcellular structures/organelles; and investigate other applications in which the probes will provide substantially greater spatial resolution and minimal invasiveness than other techniques.
In addition, the scientists might consider developing other innovations. "For example," Duan illustrates, "a major challenge in using our ultra-small probes for recording from small subcellular structures is to accurately position them with respect to the subcellular structures of interest. We're looking at either labeling our probe with fluorescence dye – or other biocompatible materials – to mark the nanotube at high resolution, or using specific targeting in which the probe's biochemical surface groups define the specific cell location being studied."