“Tools for high throughput analyses of proteins and nucleic acids in biofluids and single cells”
Protein biomarker analyses promise early and more accurate diagnosis, as well as improved selection and monitoring of optimal therapy, but assay performance so far has been limiting for discovery and monitoring of biomarkers. Antibody-based proximity ligation or extension assays yield reporter DNA strands for convenient, highly sensitive and specific recording of target proteins. The DNA readout helps to avoid mounting problems with crossreactivity upon multiplexing, permitting high throughput protein detection in 1ųl aliquots of plasma samples. In Uppsala alone the method has now been used for several millions of protein determinations in large cohorts of patients and controls. We have also applied the assays to establish optimal conditions for collecting samples, including as dried blood spots on filter papers. The sensitivity of the assays permits multiplex protein measurements even in single cells, to better characterize their responses to therapeutic regimens. For particularly demanding applications, modified proximity assays provide further enhanced sensitivity and specificiity of detection of protein markers present at very low concentrations.
We are also developing a highly specific and sensitive method for digital detection of rare DNA molecules including tumor specific mutant sequences in plasma, revealing their origin in tumors from patients with malignant disease, in order to monitor the progress of disease and of therapy.
The molecular tools for both protein and DNA detection techniques also lend themselves for high-performance detection of infectious agents