Biological tissue is  rarely transparent, presenting major challenges for deep tissue optical microscopy. Due to its high-resolution and viewing of live organisms, optical microscopy has become an important tool for biological research and continues to open new avenues in its capabilities. In recent years, image resolution and speed has dramatically improved. However, the resolution and penetration depth is still in great need of improvement. The problem is caused by light being absorbed, refracted and scattered as it passes through biological tissue, limiting the resolution and depth of optical imaging. Overcoming these challenges will benefit a wide range of applications from basic biological research to clinical investigations.

Genotoxic (DNA damage-inducing) chemicals often increase the risk of cancer. Genotoxicity testing is mandatory for approval of new drugs as an indicator of potential carcinogenicity and is therefore generally undesired. The Ames test is the most widely-used genotoxicity assay and is required by regulatory agencies for the registration and approval of new chemicals. This test uses Salmonella and E. coli as model organisms because of the exquisite conservation of DNA damage and repair mechanisms across kingdoms. The Ames Test is a mutation reversion test; the assay can be performed on solid plates (Ames plate incorporation test) or in a liquid version (Ames fluctuation assay). The primary difficulty is the large amount of compound required, and even the miniaturized versions of Ames (solid, mini-Ames), requires >10mg of test compound. Thus, the use of this assay to detect mutagenic activity during early stages of drug discovery (when typically, little amount of compound is available), or in complex mixtures of compounds (where the active compound may be a small fraction of the total), is limited. The high sample amount also limits the ability for biomonitoring of environmental mutagens in typical environmental mixtures. UCSC researchers have developed technology based on the same principles as the Ames test, but is far more sensitive and provides quantitative information. The inventors have developed a novel method for the detection of chemical mutagenesis that requires only a fraction of the sample used in Ames, at minimum 100-fold less. The information provided in a 96-well plate for the liquid Ames test could be obtained in one well, dramatically reducing the amount of test sample required, and the method can be used for both drug discovery and environmental biomonitoring. Also, it may be used to screen high-yield natural products libraries for compounds targeting DNA as potential antimicrobial, anti-inflammatory or antitumor agents.