Nano and micro technologies provide new solutions for increasing the speed and accuracy of identifying genes and genetic materials for drug discovery and development,and for treatment-linked disease diagnostics products.

Thousands of genes and their products (i.e. RNA and proteins) function in a complicated and orchestrated manner. Genetic testing technologies used for drug discovery and in diagnostic products make it possible to measure gene sequences (i.e. genes, gene mutations) and gene expression levels (abundance), which are important indicators of growth, metabolism, development, behavior and adaptation of living systems. With these tools, many different genes and expression patterns can be characterized as normal or diseased tissue, along with the various stage of disease.

There are many steps and processes involved in genetic testing. While the nature of the tests and nomenclature may vary, some of the key principals and related challenges are described below.

Step 1 – Create or obtain DNA arrays of “known” probes
Known probes of genetic sequences are prepared or obtained commercially for a desired test. These probes are typically in the form of cDNA or an array of oligonucleotides. While it is desirable to have as many probes as possible to maximize the search for possible results, there is currently a limited number of known specimens. This limits the range of experimentation for drug discovery and disease diagnostics. With advances in the human genome, gene cloning and molecular biology, a vast amount of new probes are increasingly available which could in time cover the entire genome, and potentially screen multiple targets in a single test.

DNA arrays are created by placing probes as individual spots in an orderly array arrangement on a glass microscope slide, a nylon membrane substrate or a silicon chip. The latter case is also referred to as a biochip.

Step 2 – Collect and assay “unknown” targets
Unknown cells or molecules of interest (called “targets”) need to be collected and then compared with the known probes in the DNA array. This begins with tissue, blood or other biological samples where nucleic acids (RNA or DNA) are isolated.

The nucleic acids are converted into labeled targets by tagging the DNA marker with an observable fluorescent or radioactive label. The labeled targets are incubated with the probes to permit hybridization and form stable DNA and/or RNA duplex. This is used for locating or identifying nucleotide sequences of interest. After the incubation, nonhybridized samples are washed away, and measurements are made of the signal produced when hybridization occurs at particular probe locations. The level of hybridization between a specific probe and a target indicates the level of the gene corresponding to that probe in the test solution.

Current assay technologies use fluorescent dyes to label molecules and require expensive equipment such as a laser to light up biological interactions, and an optical microscope to detect the binding sites. Fluorescent dyes are not always precise or sufficiently sensitive to detect every gene. Also, genes that are not distinguished separately can bleed together and result in a false or inconsistent result.

The hybridization may also require gene amplification or Polymerase Chain Reaction (PCR) which is used to produce millions of copies of a specific piece of DNA in a test tube from a single cell. Amplification could require a repetitive series of cycles making use of various chemical and processing stages.