Biosensors

Micro- and nanoengineering technologies offer revolutionary possibilities for biosensors and sensor arrays for drug and chemical screening and environmental monitoring. When a cell membrane detects (senses) a target molecule, it can turn electrical currents on or off by opening or closing molecular channels. When the channels are open, charged ions can pass in or out of the cell. These ions would not pass through the otherwise insulating membrane. When these channels open, the ion flow creates a potential difference across the membrane, which in turn creates a current. Such ffiĆ­lffl

- lipid monolayer

- alkyl thiols sSi' I

Si I

lipid bilayer SiO2

lipid bilayer SiO2

-lipid bilayer

O-SrO-Sr

Figure 62. Architectures of supported membranes [126]. Three basic strategies are sketched here, together with some possibilities for their realization. (A) A phospholipid monolayer on a hydrophilic base layer, which in most cases consists of rigidly packed alkyl chains. This base layer may be produced by the self-assembly of alkylthiols on gold (a), of alkylsilanes on oxide surfaces (b), by the Langmuir-Blodgett (LB) transfer of a monolayer of fatty acid salts to a hydrophilic surface (c), or by the coupling of a rigid hydrophilic polymer to the surface (not shown). The phospholipid monolayer on top is either formed by entropy-driven self-assembly in solution or transferred horizontally from the air-water interface. This monolayer configuration is suited for the observation of processes on the membrane surface or for anchoring peripheral membrane proteins. (B) A phospholipid bilayer on a hydrophilic surface. This surface may be a clean glass, quartz, or silicon oxide surface on which bilayers may be formed by vesicle spreading or by two-step LB transfer. Gold surfaces must be functionalized with hydroxy-, carboxy-, or amino-terminated thiols to confer hydrophilicity; for bilayer spreading, surface charge can be exploited by using charged lipids (d). The formation of bilayers supported on a hydrophilic polymer is also possible (e). The incorporation of transmembrane proteins in such a "coating" bilayer has been demonstrated. (C) An anchored phospholipid bilayer on a hydrophilic surface. To mimic the natural situation more closely, phospholipid derivatives must be used as hydrophilic anchors for the membrane, and the interstices on the surface must either expose a hydrophilic material or be correspondingly functionalized. Anchor lipids may be thiolipids on gold (f), lipids coupled by a cross-linker to oxide surfaces (g), His-lipids, succinimidyl-lipids, etc. In this configuration, the membrane must be formed by self-assembly from vesicle suspensions or detergent solutions; it is well suited for the accommodation of transmembrane proteins. Courtesy of S. Heyse, Biochimica et Biophysica Acta.

biosensors have a huge range of potential uses, especially in medicine, for detecting drugs, hormones, viruses, and pesticides and to identify gene sequences for diagnosing genetic disorders. The ability to detect the modulation of cell membrane channel activity by the binding of therapeutic agents is considered crucial for rational and efficient drug discovery and design. Since combinatorial libraries of potential therapeutic compounds are rapidly growing, fast and highly

Au c

Au sensitive methods for functional drug screening are required. An attractive possibility is the use of self-assembled tethered membranes containing specific channel receptors as the sensing element in an otherwise solid-state biosensing device. Massive arrays of individually addressable microsensors with integrated fluid handling are conceivable. Even very simple sensor designs offer valuable advances in low-cost sensing for clinical medicine and the food and hygiene sectors. The much-discussed "artificial nose" containing a dense array of receptor sites affording unambiguous identification of molecular species could analyze the breath of patients for known chemical signatures of diseases such as liver cirrhosis and lung cancer.

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