nanotechnology Bioassays

A second area of intense study in nanomedicine is that of developing new diagnostic tools. Motivation for this work ranges from fundamental biomedical research at the level of single genes or cells to point-of-care applications for health delivery services. With advances in molecular biology, much diagnostic work now focuses on detecting specific biological “signatures.” These analyses are referred to as bioassays. Examples include studies to determine which genes are active in response to a particular disease or drug therapy. A general approach involves attaching fluorescing dye molecules to the target biomolecules in order to reveal their concentration.

Another approach to bioassays uses semiconductor nanoparticles, such as cadmium selenide, which emit light of a specific wavelength depending on their size. Different-size particles can be tagged to different receptors so that a wider variety of distinct colour tags are available than can be distinguished for dye molecules. The degradation in fluorescence with repeated excitation for dyes is avoided. Furthermore, various-size particles can be encapsulated in latex beads and their resulting wavelengths read like a bar code. This approach, while still in the exploratory stage, would allow for an enormous number of distinct labels for bioassays.

Another nanotechnology variation on bioassays is to attach one half of the single-stranded complementary DNA segment for the genetic sequence to be detected to one set of gold particles and the other half to a second set of gold particles. When the material of interest is present in a solution, the two attachments cause the gold balls to agglomerate, providing a large change in optical properties that can be seen in the colour of the solution. If both halves of the sequence do not match, no agglomeration will occur and no change will be observed.

Approaches that do not involve optical detection techniques are also being explored with nanoparticles. For example, magnetic nanoparticles can be attached to antibodies that in turn recognize and attach to specific biomolecules. The magnetic particles then act as tags and “handlebars” through which magnetic fields can be used for mixing, extracting, or identifying the attached biomolecules within microlitre- or nanolitre-sized samples. For example, magnetic nanoparticles stay magnetized as a single domain for a significant period, which enables them to be aligned and detected in a magnetic field. In particular, attached antibody–magnetic-nanoparticle combinations rotate slowly and give a distinctive magnetic signal. In contrast, magnetically tagged antibodies that are not attached to the biological material being detected rotate more rapidly and so do not give the same distinctive signal.

Microfluidic systems, or “labs-on-chips,” have been developed for biochemical assays of minuscule samples. Typically cramming numerous electronic and mechanical components into a portable unit no larger than a credit card, they are especially useful for conducting rapid analysis in the field. While these microfluidic systems primarily operate at the microscale (that is, millionths of a metre), nanotechnology has contributed new concepts and will likely play an increasing role in the future. For example, separation of DNA is sensitive to entropic effects, such as the entropy required to unfold DNA of a given length. A new approach to separating DNA could take advantage of its passage through a nanoscale array of posts or channels such that DNA molecules of different lengths would uncoil at different rates.

Other researchers have focused on detecting signal changes as nanometre-wide DNA strands are threaded through a nanoscale pore. Early studies used pores punched in membranes by viruses; artificially fabricated nanopores are also being tested. By applying an electric potential across the membrane in a liquid cell to pull the DNA through, changes in ion current can be measured as different repeating base units of the molecule pass through the pores. Nanotechnology-enabled advances in the entire area of bioassays will clearly impact health care in many ways, from early detection, rapid clinical analysis, and home monitoring to new understanding of molecular biology and genetic-based treatments for fighting disease.