Publications by authors named "Anne E Jensen"

5 Publications

  • Page 1 of 1

Development and validation of a cellular host response test as an early diagnostic for sepsis.

PLoS One 2021 15;16(4):e0246980. Epub 2021 Apr 15.

Louisiana State University Health Sciences Center, Baton Rouge, Louisiana, United States of America.

Sepsis must be diagnosed quickly to avoid morbidity and mortality. However, the clinical manifestations of sepsis are highly variable and emergency department (ED) clinicians often must make rapid, impactful decisions before laboratory results are known. We previously developed a technique that allows the measurement of the biophysical properties of white blood cells as they are stretched through a microfluidic channel. In this study we describe and validate the resultant output as a model and score-the IntelliSep Index (ISI)-that aids in the diagnosis of sepsis in patients with suspected or confirmed infection from a single blood draw performed at the time of ED presentation. By applying this technique to a high acuity cohort with a 23.5% sepsis incidence (n = 307), we defined specific metrics-the aspect ratio and visco-elastic inertial response-that are more sensitive than cell size or cell count in predicting disease severity. The final model was trained and cross-validated on the high acuity cohort, and the performance and generalizability of the model was evaluated on a separate low acuity cohort with a 6.4% sepsis incidence (n = 94) and healthy donors (n = 72). For easier clinical interpretation, the ISI is divided into three interpretation bands of Green, Yellow, and Red that correspond to increasing disease severity. The ISI agreed with the diagnosis established by retrospective physician adjudication, and accurately identified subjects with severe illness as measured by SOFA, APACHE-II, hospital-free days, and intensive care unit admission. Measured using routinely collected blood samples, with a short run-time and no requirement for patient or laboratory information, the ISI is well suited to aid ED clinicians in rapidly diagnosing sepsis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246980PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049231PMC
April 2021

Enhanced Isolation and Release of Circulating Tumor Cells Using Nanoparticle Binding and Ligand Exchange in a Microfluidic Chip.

J Am Chem Soc 2017 02 9;139(7):2741-2749. Epub 2017 Feb 9.

Department of Chemistry, Sahmyook University , Seoul, 01795, Korea.

The detection of rare circulating tumor cells (CTCs) in the blood of cancer patients has the potential to be a powerful and noninvasive method for examining metastasis, evaluating prognosis, assessing tumor sensitivity to drugs, and monitoring therapeutic outcomes. In this study, we have developed an efficient strategy to isolate CTCs from the blood of breast cancer patients using a microfluidic immune-affinity approach. Additionally, to gain further access to these rare cells for downstream characterization, our strategy allows for easy detachment of the captured CTCs from the substrate without compromising cell viability or the ability to employ next generation RNA sequencing for the identification of specific breast cancer genes. To achieve this, a chemical ligand-exchange reaction was engineered to release cells attached to a gold nanoparticle coating bound to the surface of a herringbone microfluidic chip (NP-CTC-Chip). Compared to the use of the unmodified CTC-Chip, our approach provides several advantages, including enhanced capture efficiency and recovery of isolated CTCs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/jacs.6b12236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5506378PMC
February 2017

NF2/Merlin mediates contact-dependent inhibition of EGFR mobility and internalization via cortical actomyosin.

J Cell Biol 2015 Oct 19;211(2):391-405. Epub 2015 Oct 19.

Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA 02129 Department of Pathology, Massachusetts General Hospital, Charlestown, MA 02129 Department of Pathology, Harvard Medical School, Boston, MA 02115

The proliferation of normal cells is inhibited at confluence, but the molecular basis of this phenomenon, known as contact-dependent inhibition of proliferation, is unclear. We previously identified the neurofibromatosis type 2 (NF2) tumor suppressor Merlin as a critical mediator of contact-dependent inhibition of proliferation and specifically found that Merlin inhibits the internalization of, and signaling from, the epidermal growth factor receptor (EGFR) in response to cell contact. Merlin is closely related to the membrane-cytoskeleton linking proteins Ezrin, Radixin, and Moesin, and localization of Merlin to the cortical cytoskeleton is required for contact-dependent regulation of EGFR. We show that Merlin and Ezrin are essential components of a mechanism whereby mechanical forces associated with the establishment of cell-cell junctions are transduced across the cell cortex via the cortical actomyosin cytoskeleton to control the lateral mobility and activity of EGFR, providing novel insight into how cells inhibit mitogenic signaling in response to cell contact.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1083/jcb.201503081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4621825PMC
October 2015

Biodegradable nano-films for capture and non-invasive release of circulating tumor cells.

Biomaterials 2015 Oct 20;65:93-102. Epub 2015 Jun 20.

Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.

Selective isolation and purification of circulating tumor cells (CTCs) from whole blood is an important capability for both clinical medicine and biological research. Current techniques to perform this task place the isolated cells under excessive stresses that reduce cell viability, and potentially induce phenotype change, therefore losing valuable information about the isolated cells. We present a biodegradable nano-film coating on the surface of a microfluidic chip, which can be used to effectively capture as well as non-invasively release cancer cell lines such as PC-3, LNCaP, DU 145, H1650 and H1975. We have applied layer-by-layer (LbL) assembly to create a library of ultrathin coatings using a broad range of materials through complementary interactions. By developing an LbL nano-film coating with an affinity-based cell-capture surface that is capable of selectively isolating cancer cells from whole blood, and that can be rapidly degraded on command, we are able to gently isolate cancer cells and recover them without compromising cell viability or proliferative potential. Our approach has the capability to overcome practical hurdles and provide viable cancer cells for downstream analyses, such as live cell imaging, single cell genomics, and in vitro cell culture of recovered cells. Furthermore, CTCs from cancer patients were also captured, identified, and successfully released using the LbL-modified microchips.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biomaterials.2015.06.036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4827098PMC
October 2015

Tunable nanostructured coating for the capture and selective release of viable circulating tumor cells.

Adv Mater 2015 Mar 15;27(9):1593-9. Epub 2015 Jan 15.

Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, Building 114, 16th Street, Charlestown, MA, 02129, USA; Shriners Hospital for Children, Harvard Medical School, 51 Blossom Street, Boston, MA, 02114, USA; Department of Surgery, Massachusetts General Hospital, Harvard Medical School 55, 55 Fruit Street, Boston, MA, 02114, USA.

A layer-by-layer gelatin nanocoating is presented for use as a tunable, dual response biomaterial for the capture and release of circulating tumor cells (CTCs) from cancer patient blood. The entire nanocoating can be dissolved from the surface of microfluidic devices through biologically compatible temperature shifts. Alternatively, individual CTCs can be released through locally applied mechanical stress.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/adma.201404677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4492283PMC
March 2015