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Detailed combustion studies have historically been conducted in simplified reacting systems, such as shock-tubes and rapid compression machines. The reciprocating internal combustion engine presents many challenges when used to isolate the effects of fuel chemistry from thermodynamics. On the other hand, the conditions in such engines are the most representative in terms of pressure and temperature histories. This paper describes the use of a single-cylinder research engine as an advanced reactor to better determine fuel effects experimentally. In particular, a single-cylinder engine was operated in a manner that allowed the effects of changes in charge composition and temperatures to be isolated from changes in equivalence ratio. An example study is presented where the relative effects of low-temperature and high-temperature chemistry, and their effects on combustion phasing, are isolated and examined.