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Circulating cell-free DNA (ccf-DNA) is becoming an important biomarker for cancer diagnostics and therapy monitoring. The isolation of ccf-DNA from plasma as a \"liquid biopsy\" may begin to replace more invasive tissue biopsies for the detection and analysis of cancer-related mutations. Conventional methods for the isolation of ccf-DNA from plasma are costly, time-consuming, and complex, preventing the use of ccf-DNA biomarkers for point-of-care diagnostics and limiting other biomedical research applications. We used an AC electrokinetic device to rapidly isolate ccf-DNA from 25 μL unprocessed blood. ccf-DNA from 15 chronic lymphocytic leukemia (CLL) patients and 3 healthy individuals was separated into dielectrophoretic (DEP) high-field regions, after which other blood components were removed by a fluidic wash. Concentrated ccf-DNA was detected by fluorescence and eluted for quantification, PCR, and DNA sequencing. The complete process, blood to PCR, required <10 min. ccf-DNA was amplified by PCR with immunoglobulin heavy chain variable region (IGHV)-specific primers to identify the unique IGHV gene expressed by the leukemic B-cell clone, and then sequenced. PCR and DNA sequencing results obtained by DEP from 25 μL CLL blood matched results obtained by use of conventional methods for ccf-DNA isolation from 1 mL plasma and for genomic DNA isolation from CLL patient leukemic B cells isolated from 15-20 mL blood. Rapid isolation of ccf-DNA directly from a drop of blood will advance disease-related biomarker research, accelerate the transition from tissue to liquid biopsies, and enable point-of-care diagnostic systems for patient monitoring.

Common epifluorescent microscopy does not provide the sensitivity to detect low levels of important analytes, such as drug delivery nanoparticles or disease biomarkers. Advanced optical elements may be used to improve performance, but greatly increase the cost of the system. In this thesis, an epifluorescent microscope has been combined with a microelectrode array employing dielectrophoresis (DEP) to concentrate and capture nanoparticulates into defined areas; this process shown to enable low level detection below a clinically significant level. The cost of the microscope and microelectrode array analytical system is substantially lower than other advanced optical detection systems.

Background Cancer stem cells (CSCs) are purported to be responsible for tumor initiation, treatment resistance, disease recurrence, and metastasis. CXCR1, one of the receptors for CXCL8, was identified on breast cancer (BC) CSCs. Reparixin, an investigational allosteric inhibitor of CXCR1, reduced the CSC content of human BC xenograft in mice. Methods In this multicenter, single-arm trial, women with HER-2-negative operable BC received reparixin oral tablets 1000 mg three times daily for 21 days before surgery. Primary objectives evaluated the safety of reparixin and the effects of reparixin on CSC and tumor microenvironment in core biopsies taken at baseline and at treatment completion. Signal of activity was defined as a reduction of ≥ 20% in ALDH + or CD24 − /CD44 + CSC by flow cytometry, with consistent reduction by immunohistochemistry. Results Twenty patients were enrolled and completed the study. There were no serious adverse reactions. CSC markers ALDH + and CD24 − /CD44 + measured by flow cytometry decreased by ≥ 20% in 4/17 and 9/17 evaluable patients, respectively. However, these results could not be confirmed by immunofluorescence due to the very low number of CSC. Conclusions Reparixin appeared safe and well-tolerated. CSCs were reduced in several patients as measured by flow cytometry, suggesting targeting of CXCR1 on CSC. Clinical trial registration Clinicaltrials.gov, NCT01861054. Registered on April 18, 2013.

An amendment to this paper has been published and can be accessed via the original article.