The objective of this proposal is to develop novel instruments for measurements not possible using existing techniques. The unique properties of acousto-optic tunable filters (AOTFs) are to be exploited. Specifically, the ability of the AOTF to give diffracted light at more than one wavelength with each wavelength modulated at a different frequency will be synergistically combined with the thermal lens technique to make a multiwavelength infrared thermal lens detector for capillary electrophoresis (CE) with virtually zero background, high sensitivity, and universality. Additionally, the detector will be capable of identifying functional groups in a sample through their IR chromophores. The detector may be particularly useful for sequencing of macromolecules such as DNA. A sensitive and universal chiral detector for HPLC and CE will be developed by combining the thermal lens effect with the AOTF to measure vibrational circular dichroism. An AOTF for the UV and visible regions will be made for subsequent construction of a rapid scanning absorption and circular dichroism (CD) detector for HPLC. Advantages of the recently developed integrated-AOTF will then be taken to miniaturize the instruments and to provide them with additional features such as faster scan capability and elimination of realignment. Finally, the AOTF's ability to diffract light coming from different positions of an object with different wavelengths will be exploited to make a detector for gel and capillary array electrophoresis (GE and CAE) that has true supermultispectral imaging capability (i.e., it is capable of recording spectra for each point of an object with spatial resolution so high that it is comparable to the spectral resolution). Because this detector has high sensitivity and higher throughput the other detectors, it may provide a major breakthrough for DNA sequencing. Collectively, results obtained will provide the necessary instruments that scientists can easily use to detect sensitively and rapidly and (chemically and stereochemically) to determine chemical and biochemical samples (e.g., carcinogenic compounds, drugs, DNA, proteins) as they are separated by HPLC, CE, and GE. The contribution of these instruments to the human genome project will be invaluable because they will provide substantial increases in the throughputs of the GE and CAE techniques.
