September 28, 2008


By Shelley, Suzanne

Innovations in Micro- and Nanotechnology to Measure Living Cells Living cells are complicated bioreactors with a plethora of multi- stage reaction sequences occurring simultaneously to sustain life. Through the development of more-sophisticated nanostructures and microdevices, chemical engineers are better able to measure and monitor these cellular and subcellular processes. Cell analysis over the last 25 years has traditionally been performed at the macro scale. However, today's microfabricated laboratories on a chip are able to interface micronscale events and sensors with cell populations.

Micro- and nanoscale technologies are now routinely used to probe and manipulate living cells. Dr. Adrienne R. Minerick, of Mississippi State Univ., describes in the September AIChE Journal perspective, "The Rapidly Growing Field of Micro and Nanotechnology to Measure Living Cells," the progress that has been made in utilizing microscale devices and nanotechnology to probe living cells in applications such 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, [mu]TAS) have the potential to provide high resolution, low cost, and rapid analysis of small samples and are under development for a wide range of biological and chemical applications. Such devices are designed to mimic laboratory processes in microliter and nanoliter volumes by utilizing microchannels and microchambers fabricated into polymer or glass chips. Living cells can easily be studied within this platform because precisely controlled environmental conditions and single cell manipulations are now possible.

The Silicon Revolution developed technology that has provided the foundation for many of today's microfluidic systems. Fabrication techniques for micro- and nanoscale features are diverse, and include soft photolithography, injection molding, glass acid etching, laser ablation, hydrophobic surface patterning, and LiGA (which combines lithography, electroplating and molding), among others. Cell culture, cell population analysis, and single cell manipulation have been accomplished in systems fabricated by these methods. Polymers are the most common platform for microfluidic devices due to the ease of channel fabrication, their tunable chemical, mechanical, electrical and optical properties, and lower material costs.

In order for microfluidic devices to achieve the goal of fully inclusive tiny laboratories on a chip, they must mimic multi-step analytical procedures with nanoliter volumes of reagents and samples. From a chemical engineering perspective, it is necessary to re-engineer key unit operations at the microscale by taking advantage of forces that are much more significant at these small length scales. These unit operations include transport, dilution, mixing, thermal control, concentration, separation and detection.

Nanotechnology for mechanical, biochemical and electrical probing of living cells and subcellular-level events is diverse. In the article, Minerick discusses single particle interactions with cells that influence or change cell properties for greater contrast, optical tagging, changes in susceptibility to forces, or penetration of the cell membrane. Structures with nanoscale features can play a significant role in the manipulation and characterization of living cells. Also, nanoscaffolds can provide a framework for tissue growth and can have a significant impact on tissue properties, regeneration and strength, and the controlled release of drugs.

Nanoscale structures exhibit different properties than their bulk counterparts. Many nanoparticles utilized with living cells are functionalized with antibodies or other biological molecules exhibiting high levels of specificity and selectivity. These antibody interactions have been previously characterized by immunologists, cloned, amplified within animals or in vitro, harvested, and then purified. For most nanoparticle binding, a linker molecule is required, such as mercaptopropyltriethoxysilane (MPTS), which has an affinity for gold nanoparticles and also has exposed functional groups with an affinity for desired antibodies.

Noninvasive imaging of living cells or tissues is possible with nanoparticles or quantum dots as contrast agents; they can be incorporated into the cells via endocytotic mechanisms or simply linked onto the cell surfaces.

Nanoparticles can also be bound to cells for subsequent magnetic or electrical manipulation. For example, superparamagnetic beads were bound to transmembrane receptors of target cells with monovalent ligands. When placed in a magnetic field, the beads became magnetized and caused the cells to aggregate. Due to the proximity of the transmembrane receptors, biological responses such as calcium influx into the cell occurred only when exposed to the field.

Minerick believes that the future will produce even more creative strategies for chemical engineers to study and manipulate living cells that rely on both microfluidics and nanoscale probes. Microanalytical LOC devices are the key platform that will enable single cell analysis and impact medical diagnostics, biowarfare detection, pharmaceutical testing and many other chemical analysis applications.

Copyright American Institute of Chemical Engineers Sep 2008

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