University of Pennsylvania

Stephen M Hahn

Gary D Kao

Jay F Dorsey

Emigdio Reyes

Arjun Gaurang Yodh

Harry Quon

Emile R Mohler, Iii

Turgut Durduran

Mark G Burnett

Joel H Greenberg

Guoqiang Yu

John A Detre

A method useful for identifying and isolating live circulating tumor cells is described. The method utilizes an adenoviral vector comprising a replication-competent adenovirus in which the E1 gene region is expressed under the control of a telomerase-specific promoter and further comprises a second expression cassette containing a marker protein, optionally fused to a detectable cell surface marker to permit detection of circulating tumor cells lacking cell surface markers. The method involves combining ex vivo a test sample from a patient suspected of having circulating tumor cells, an adenoviral probe system, and culture media for the cells. The test sample is incubated with the adenoviral system for a sufficient time to permit expression of the reporter protein. The marker gene expression can thereafter be quantitated and the marker-expressing cells may optionally be collected for further analysis.

Compositions and methods for isolation of circulating tumor cells (CTC)

A repeatable method for detecting circulating tumor cells in vitro is provided. The method involves combining a test sample from a patient suspected of having circulating tumor cells, and a non-lytic adenoviral system, and culture media for the cells. The adenoviral system utilizes (i) a first replication-defective adenoviral particle in which an expression cassette is packaged, said expression cassette comprising an adenoviral 5' and 3&#x2032; ITRs and a tumor-specific promoter; and (ii) a coding sequence for a reporter protein which is expressed in the presence of circulating tumor cells, and an adenoviral 3&#x2032; ITR. The test sample and the non-lytic adenoviral system are incubated for a sufficient time to permit expression of the reporter protein, and measuring reporter protein expression in the test samples, whereby presence of reporter expression indicates the presence of circulating tumor cells in the sample. Because the system is non-lytic, the testing can be repeated on the cells which remain viable in culture. Also provided is a method for enriching test samples having circulating tumor cells and a microfluidics device suitable for CTC-specification identification and enumeration.

Compositions, methods and microfluidics device for telomerase based in vitro diagnostic assays for detecting circulating tumor cells (CTC)

A repeatable method for detecting circulating tumor cells in vitro is provided. The method involves combining a test sample from a patient suspected of having circulating tumor cells, and a non-lytic adenoviral system, and culture media for the cells. The adenoviral system utilizes (i) a first replication-defective adenoviral particle in which an expression cassette is packaged, said expression cassette comprising an adenoviral 5' and 3&#x2032; ITRs and a tumor-specific promoter; and (ii) a coding sequence for a reporter protein which is expressed in the presence of circulating tumor cells, and an adenoviral 3&#x2032; ITR. The test sample and the non-lytic adenoviral system are incubated for a sufficient time to permit expression of the reporter protein, and measuring reporter protein expression in the test samples, whereby presence of reporter expression indicates the presence of circulating tumor cells in the sample.

An embodiment of the invention includes a device, system and method for determining the characteristics of deep tissue. The novel method includes measuring blood flow rate and oxygenation characteristics of the tissue, and determining oxygen metabolism of the tissue as a function of the measure blood flow rate and measure oxygenation. The blood flow rate characteristics are measured as a function of light fluctuations caused by the tissue, while the oxygenation characteristics are measured as a function of transmission of light through the tissue with respect to the wavelength of light. The tissue may be layered tissue, for example, a portion of a brain. The tissue characteristics may be measured during times of varying levels of exercise intensity.

Optical measurement of tissue blood flow, hemodynamics and oxygenation

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Glen Mills, PA, United States of America

Stephen M Hahn