The Lodder Group at UK

a dividing line...

The science of chemical analysis is currently being redefined in light of a few simple observations:

1. Interactions between matter and energy can be identified, quantified, and reproduced, even though these interactions are not necessarily perfectly specific in the chemical sense.

2. Therefore, an instrument that measures enough interactions between matter and energy with a sufficiently high signal-to-noise ratio collects enough information to become specific in the chemical sense.

3. Combinations of simple sensing devices that can be constructed with high S/N, such as light reflectance and sound-wave propagation, allow enormous amounts of useful information about the interactions between matter and energy to be collected very quickly.

4. The analytical burden is thus shifted from high tech (and high priced) physics and chemistry, intended to reduce interferences and make the instrument more specific in the chemical sense, to the computer, which is able to sift through the enormous volumes of information about the interactions between matter and energy with ease.

Antibody chemistry and immunoassays represent the exact opposite of this approach. While a single antibody assay may be far less expensive than an analytical instrument, the assay has become so specific that huge batteries of such assays must be assembled in order to measure many analytes of interest. Often the assay kit, costing a few hundred dollars, can be used only once. In many ways much of the analytical instrumentation itself has become this specific (witness the arrival of pentaquadrupole mass spectrometers with high performance liquid chromatograph inputs and interchangeable monodisperse aerosol generators or electrospray or fast atom bombardment interfaces).

The advantages to the new approach are clear. Every year physics and chemistry and personnel and antibodies get more and more expensive and fragile and difficult to use. Every year computers get cheaper and faster and easier to repair and easier to use. The chase to measure a new analyte under the old paradigm meant the birth of a large development program culminating in the creation of an even larger monument to high technology that most labs could not afford. Measuring a new analyte under the new paradigm usually only means adding a few lines of code to a computer program.

Atherosclerosis is a difficult disease to study in terms of the growth and development of an atherosclerotic plaque or lesion. Most available methods for study of this disease use tissue removed from the site of a lesion. The major limitation of this method is that it is very difficult to examine the progression of the disease. Experiments being conducted in my laboratory use a novel method to examine the progression of an atherosclerotic lesion, with particular attention to the presence and role of oxidized LDL in lesion growth and maintenance. One method is the use of an implant which is somewhat permanently placed outside of the blood vessel where a lesion is occurring. This implant uses near-infrared light to determine the chemical constituents of an atherosclerotic lesion. This is the first developed method to study the disease as it progresses. Additionally, these experiments also examine the effect of an antioxidant drug, probucol, which prevents the chemical modification of LDL, to determine if this drug will prevent the development of an atherosclerotic lesion. These studies will greatly expand our current knowledge of atherosclerosis, and potentially serve to identify new drug therapies as well.

These distinct projects are all related by their ties to the "false-sample" problem in thought-like processes. The ubiquitousness of this problem in analytical chemistry provides endless opportunities to explore.

a divider...

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