dPCR rose out of an approach first published in 1988 by Cetus Corporation when researchers showed that a single copy of the β-globin gene could be detected and amplified by PCR. This was achieved by diluting DNA samples from a normal human cell line with DNA from a mutant line having a homozygous deletion of the β-globin gene, until it was no longer present in the reaction. In 1989, Peter Simmonds, AJ Brown et al. used this concept to quantify a molecule for the first time. Alex Morley and Pamela Sykes formally established the method as a quantitative technique in 1992.
In 1999, Bert Vogelstein and Kenneth Kinzler coined the term “digital PCR” and showed that the technique could be used to find rare cancer mutations. However, dPCR was difficult to perform; it was labor intensive, required a lot of training to do properly, and was difficult to do in large quantities. In 2003, Kinzler and Vogelstein continued to refine dPCR and created an improved method that they called BEAMing technology, an acronym for “beads, emulsion, amplification and magnetics.” The new protocol used emulsion to compartmentalize amplification reactions in a single tube. This change made it possible for scientists to scale the method to thousands of reactions in a single run.
Companies developing commercial dPCR systems have integrated technologies like automated partitioning of samples, digital counting of nucleic acid targets, and increasing droplet count that can help the process be more efficient. In recent years, scientists have developed and commercialized dPCR-based diagnostics for several conditions, including non-small cell lung cancer and Down’s Syndrome. The first dPCR system for clinical use was CE-marked in 2017 and cleared by the US Food and Drug Administration in 2019, for diagnosing chronic myeloid leukemia.