The rapidly growing field of micro and nanotechnology to measure living cells

L iving cells are complicated bioreactors with a plethora of multistage reaction sequences all occurring in concert to sustain the factory of life. As chemical engineers develop more sophisticated nanostructures and microdevices in coordination with electrical engineers and chemists, the ability to measure and monitor these cellular and subcellular processes is becoming a reality. Traditional cell analysis tools utilized over the last 25 years have predominantly been conducted at the macroscale. However, the trailing technology of the Silicon Revolution has been microfabricated laboratories on a chip (Lab-on-a-Chip), with the ability to interface micron-scale events and sensors with cell populations. The infusion of nanotechnology into this platform is even more recent and began after the National Nanotechnology Initiative’s (NNI) flurry of research in this area. Today, micro and nanoscale technologies are routinely used to probe and manipulate living cells. Although a few platforms are currently available on consumer markets, the potential for economic growth is significant. This perspective focuses primarily on the progress made utilizing microscale devices and nanotechnology to probe living cells for applications as diverse as medical diagnostics, pathogen or bioterrorism detection, pharmaceutical screening and cancer detection. Microdevices (also called Lab-on-a-Chip (LOC), and micro Total Analytical Systems (mTAS)) are under development in labs across the globe because they have the potential to provide high-resolution, low-cost, and rapid analysis with small sample volumes for a wide range of biological and chemical applications. Such microdevices are designed to mimic laboratory processes in micro and nanoliter volumes by utilizing microchannels and microchambers fabricated into polymer or glass chips. Living cells can be studied within this platform as precisely controlled environmental conditions and single-cell manipulations are now possible. Most cell manipulation technology takes advantage of the significantly different probability of object interactions that occur at the microscale. For example, examining a 10 cm section of an approximately 4 in. dia. (100 mm) pipe, one finds that the inner surface area of the pipe is 0.03 m with a corresponding volume of 0.0008 m. The surface to volume ratio for this large channel is only about 40 m, while for a microchannel with a diameter of 100 microns and the same 10 cm long, the surface area and volume are three and six orders of magnitude smaller, respectively, but the ratio of surface area to volume is three orders of magnitude larger (540,000 m). This trend is briefly captured in Table 1 for spherical particles, as well as for channels. This means that liquid/solid interactions are much more prevalent, and as such, the surfaces can be utilized to impart forces on the fluid and the cells within the channel. This surface to volume attribute can be exploited further when moving three orders of magnitude smaller to nanoparticles. For instance, one can coat a 1-micron spherical cell with over 3 million 1 nm particles (no void space 5 4 million). Functionalizing a nanoparticle is fairly straightforward, as well because over 300 1-Angstrom molecules can fit on a 1 nm particle (no void space 5 400). Molecules that are used to functionalize surfaces require a high affinity and specificity for their target molecules. Antibodies, a highly specialized biological (immunological) recognition tag, are the most commonly utilized molecules for these purposes. In this perspective, discussions will focus on microfluidic device technologies for probing cellular level processes, molecular influences on cell responses, and cell to nanoparticle interactions.