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      Evaluation of In-Flow Magnetoresistive Chip Cell—Counter as a Diagnostic Tool

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          Inexpensive simple medical devices allowing fast and reliable counting of whole cells are of interest for diagnosis and treatment monitoring. Magnetic-based labs on a chip are one of the possibilities currently studied to address this issue. Giant magnetoresistance (GMR) sensors offer both great sensitivity and device integrability with microfluidics and electronics. When used on a dynamic system, GMR-based biochips are able to detect magnetically labeled individual cells. In this article, a rigorous evaluation of the main characteristics of this magnetic medical device (specificity, sensitivity, time of use and variability) are presented and compared to those of both an ELISA test and a conventional flow cytometer, using an eukaryotic malignant cell line model in physiological conditions (NS1 murine cells in phosphate buffer saline). We describe a proof of specificity of a GMR sensor detection of magnetically labeled cells. The limit of detection of the actual system was shown to be similar to the ELISA one and 10 times higher than the cytometer one.

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          Most cited references 62

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          Continuous cultures of fused cells secreting antibody of predefined specificity.

           G Köhler,  C Milstein (1975)
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            Rapid Prototyping of Microfluidic Systems in Poly(dimethylsiloxane).

            This paper describes a procedure that makes it possible to design and fabricate (including sealing) microfluidic systems in an elastomeric material [Formula: see text] poly(dimethylsiloxane) (PDMS) [Formula: see text] in less than 24 h. A network of microfluidic channels (with width >20 μm) is designed in a CAD program. This design is converted into a transparency by a high-resolution printer; this transparency is used as a mask in photolithography to create a master in positive relief photoresist. PDMS cast against the master yields a polymeric replica containing a network of channels. The surface of this replica, and that of a flat slab of PDMS, are oxidized in an oxygen plasma. These oxidized surfaces seal tightly and irreversibly when brought into conformal contact. Oxidized PDMS also seals irreversibly to other materials used in microfluidic systems, such as glass, silicon, silicon oxide, and oxidized polystyrene; a number of substrates for devices are, therefore, practical options. Oxidation of the PDMS has the additional advantage that it yields channels whose walls are negatively charged when in contact with neutral and basic aqueous solutions; these channels support electroosmotic pumping and can be filled easily with liquids with high surface energies (especially water). The performance of microfluidic systems prepared using this rapid prototyping technique has been evaluated by fabricating a miniaturized capillary electrophoresis system. Amino acids, charge ladders of positively and negatively charged proteins, and DNA fragments were separated in aqueous solutions with this system with resolution comparable to that obtained using fused silica capillaries.
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              Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer.

              As treatment options expand for metastatic colorectal cancer (mCRC), a blood marker with a prognostic and predictive role could guide treatment. We tested the hypothesis that circulating tumor cells (CTCs) could predict clinical outcome in patients with mCRC. In a prospective multicenter study, CTCs were enumerated in the peripheral blood of 430 patients with mCRC at baseline and after starting first-, second-, or third-line therapy. CTCs were measured using an immunomagnetic separation technique. Patients were stratified into unfavorable and favorable prognostic groups based on CTC levels of three or more or less than three CTCs/7.5 mL, respectively. Patients with unfavorable compared with favorable baseline CTCs had shorter median progression-free survival (PFS; 4.5 v 7.9 months; P = .0002) and overall survival (OS; 9.4 v 18.5 months; P < .0001). Differences persisted at 1 to 2, 3 to 5, 6 to 12, and 13 to 20 weeks after therapy. Conversion of baseline unfavorable CTCs to favorable at 3 to 5 weeks was associated with significantly longer PFS and OS compared with patients with unfavorable CTCs at both time points (PFS, 6.2 v 1.6 months; P = .02; OS, 11.0 v 3.7 months; P = .0002). Among nonprogressing patients, favorable compared with unfavorable CTCs within 1 month of imaging was associated with longer survival (18.8 v 7.1 months; P < .0001). Baseline and follow-up CTC levels remained strong predictors of PFS and OS after adjustment for clinically significant factors. The number of CTCs before and during treatment is an independent predictor of PFS and OS in patients with metastatic colorectal cancer. CTCs provide prognostic information in addition to that of imaging studies.

                Author and article information

                Biosensors (Basel)
                Biosensors (Basel)
                31 August 2019
                September 2019
                : 9
                : 3
                [1 ]SPEC, CEA, CNRS, Université Paris-Saclay, CEA Saclay, CEDEX, 91191 Gif-sur-Yvette, France
                [2 ]Service de Pharmacologie et Immunoanalyse (SPI), Laboratoire d’Etudes et de Recherches en Immunoanalyse, CEA, INRA, Université Paris-Saclay, 91191 Gif-sur-Yvette, France
                [3 ]Direction des Programmes et des Partenariats Publics, Département de la Recherche Fondamentale, CEA, 91191 Gif-sur-Yvette, France
                Author notes

                These authors contributed equally to this work.

                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (


                diagnostic, gmr sensor, whole cell


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