Among the remaining challenges facing chemical analysis is the capability of extending to micro-scale samples the spectacular detection limits that have been achieved for a variety of spectroscopic methods. In such samples, a vanishingly small quantity of target analyte material, relative to background, presents a serious obstacle to achieving the rate of detection improvement that the scientific community has come to expect over the past two decades. However, a variety of problems from cell biology, electronics technology, and materials science continue to require what is best described as micro-trace composition determination. In addition, the efforts to determine the properties of single discrete entities (cells, for example) have attracted substantial interest, with much remaining room for improvement. The direction for research seeking to make this improvement is suggested from the lessons derived from successful single-atom and single-molecule detection. These milestones of spectroscopy have been achieved almost entirely by using readily available detection technology while minimizing background levels. The lesson from the progress in both fields is the axiom "Anything can be detected if the background is low enough."

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