Commentary pubs.acs.org/accounts
Advancing Ultrasensitive Molecular and Cellular Analysis Methods to Speed and Simplify the Diagnosis of Disease Published as part of the Accounts of Chemical Research special issue “Holy Grails in Chemistry”. Shana O. Kelley* Departments of Chemistry, Biochemistry, and Pharmaceutical Sciences and the Institute for Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Canada M5S 3M2 ABSTRACT: Diagnosing disease at the molecular level rapidly and with a high level of sensitivity and specificity is a critical capability for modern medicine. Rapid detection of small numbers of biomarkers of early disease in complex, heterogeneous clinical specimens represents a Holy Grail that will have a significant impact on human health.
O
and (iii) establishing versatile and cost-effective ($10) methods that will make routine molecular testing available for personalized medicine to be implemented. Realizing these advances will have profound implications, including the realization of significant decreases in deaths from metastatic cancer, the control of antimicrobial resistance, and improved outcomes for patients in need of organ transplants. In this Commentary, the challenging problems that must be solved (Figure 1) are outlined and the solutions and benefits they would bring are highlighted.
ur understanding of the molecular-level basis of human disease is progressing at an impressive pace. The molecular properties of different cancer subtypes are increasingly known and exploited to produce new, tailormade therapies.1 The genetic fingerprints of infectious pathogens can be identified and used to develop effective treatments and control outbreaks.2 Personalized medicine based on genetic-level information is becoming a reality for the treatment of many rare and common diseases.3 Nevertheless, there exist many diseases today that are not diagnosed early or rapidly enough to enable effective treatments to be administered. Infectious diseases like Ebola, SARS, and Zika cause public health crises that are difficult to control. Other types of infections are treated empirically based on symptoms, rather than molecular-level information, and this contributes to the growing prevalence of antibiotic-resistant infections. Cancer is often diagnosed once already metastatic and difficult to treat. As well, the use of genetic information to predict individual patients’ responses to therapeutics is not routine, which limits the effectiveness of the management of many different types of disease. Disease diagnosis, if performed at the molecular level rather than empirically based on symptoms, relies on detecting trace levels of biomarkers and on capturing rare cells and infectious organisms with high levels of sensitivity and specificity. It is essential that we continue to advance the performance and availability of new analytical methods that will enhance our ability to detect the markers of disease at early stages when curative therapies are most effective. The Holy Grails related to earlier and faster disease diagnosis include (i) developing new noninvasive screening methods that detect cancerous tumors at an early stage while they are localized, (ii) making available molecular-level tests that allow infectious disease to be diagnosed rapidly (
