Detection of adhesion resistance in cells or lipid membranes by noise analysis
Sensoren, Geräte und Komponenten
The voltage fluctuations in the adhesion area of nerve cells from rat brain, which are cultured on oxidized silicon. As a probe, an electrolyte oxide-silicon field-effect transistor is used as sketched in Fig. 2(b). It consists of an open gate between source and drain contacts and is insulated from the electrolyte by 10 nm silicon dioxide. A local change of voltage in the electrolyte layer between cell and chip gives rise to a modulation of source-drain current. Because of a buried channel configuration, the transistor has a particularly low 1/f noise. The gate with a dimension of 6µm × 7µm is small enough to be completely covered by a mammalian nerve cell, but large enough to avoid a dominance of the 1/f noise that increases with decreasing gate area.
This method allows the direct electrical interfacing of a semiconductor device to an individual mammalian nerve cell. The firing neuron directly controls the source-drain current of a buried channel electrolyte-oxide-silicon (EOS) field-effect transistor. Experiments demonstrate the feasibility of noninvasive monitoring of neuronal systems by semiconductor chips at the level of individual cells and lay the foundation for applications of very large scale integration technology in neuroscience and pharmacology.
The recording and analysis of voltage noise can be applied not only for cell adhesion, but also for other contacts of organic films and solids in electrolyte, such as supported lipid membranes without or with membrane proteins.
Experiments demonstrate that thermal noise can be used as a probe for the electrical properties of cell adhesion. In comparison to other methods, this approach does not require a perturbation of the cells, e.g., staining with a dye or contacting with a pipette, nor any external stimulation. This novel technique is non-invasive, does not rely on molecular probes and does not require any intra or extracellular stimulation.
In addition to the observation of cell adhesion, the adhesion noise has a general relevance for extracellular recording; as for frequencies above 1.5 kHz the observed adhesion noise is larger than all other noise sources combined, which means that the thermodynamic limit of extracellular recording has been reached.
Modern semiconductor technology could provide suitable tools for massive parallel monitoring of neuronal activity at high spatial and temporal resolution.
Patent DE 102005019191, Priority Date April 4, 2005.
- M. Voelker and P. Fromherz. Nyquist noise of cell adhesion detected in a neuron-silicon transistor. Phys. Rev. Lett. 96, 228102 (2006)
- M. Voelker and P. Fromherz. Signal transmission from individual mammalian nerve cell to field-effect transistor. Small 1, 206-210 (2005)
- Ref.-No.: 0204-3316-WT (314,4 KiB)
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