Miniaturized PCR systems for cancer diagnosis

PCR retains a pivotal role in making accessible marker nucleic acid sequences for ready analysis in cancer diagnosis. For certain cancers such as acute lymphoblastic leukaemia, the application of quantitative procedures to assess and subsequently direct therapy has given rise to the slowly maturing field of MRD (minimal residual disease) management. Although excellent protocols exist for performing these analyses, akin to all PCR procedures the limit of detection can vary markedly between laboratories. The present paper is an overview that describes how the analytical field relating to miniaturization is likely to identify the missing link that integrates sample processing with downstream PCR, analysis and eventual therapy. Miniaturized devices are suited to the multi-parallelized handling of defined numbers of cells, and PCR-based microfluidic procedures have become reasonably established. The integration of sample processing and PCR in microfluidic devices is beginning to offer reproducible quantitative data that relate the number of biomarker nucleic acids to the defined analysed cell or cells for meaningful clinical assessment. The application of MRD may, through integrated miniaturized PCR, become more reliable and routine with additional applications in defining disease threshold levels for other cancer types. These enabling integrated platforms may facilitate biomarker measurements to predict the response and outcome, which are also of current interest for personalized medical care.