Creatv Microtech, Inc.

USA As Represented by Secretary of the Navy

Other

Government of the United States of America, As Represented by the Secretary of Commerce

Creative Micro Tech, Inc.

Cha-Mei Tang

Daniel E Adams

Olga V Makarova

Platte T Amstutz

Peixuan Zhu

Thomas A Swyden

Shuhong Li

Antonio C Ting

Daniel Adams

Yunqi Zhang

Cha-Min Tang

Richard D Deslattes

Guohua Yang

Platte T Amstulz, Iii

Daniel L Adams

Methods of using detection of PD-L1 expression by circulating cancer cells in the screening, monitoring, treatment and diagnosis of cancer in subjects are disclosed. The methods are based on assaying one or more of circulating tumor cells (CTCs), epithelial to mesenchymal transition CTCs (EMTCTCs), cancer associated macrophage-like cells (CAMLs), and cancer associated vascular endothelial cells (CAVEs) isolated from a subject having cancer for PD-L1 expression.

Methods of using PD-L1 expression in treatment decisions for cancer therapy

Circulating tumor cells (CTCs) are associated with metastasis of malignant solid tumors in a patient. Presented here is evidence that CTCs exhibit cell cycle phase variability and that there is a strong correlation between the number of CTCs in a mitotic cell cycle phase and the prospects for long term survival of the subject from which the cells were obtained. Also presented herein are methods of determining the mitotic cell cycle phase of CTCs from a patient having cancer and using the information in grading malignant solid tumors and predicting the likelihood of survival of the patient.

Use of circulating tumor cell mitotic index in cancer stratification and diagnostics

A microfilter having a hydrophilic surface and suited for size-based capture and analysis of cells, such as circulating cancer cells, from whole blood and other human fluids is disclosed. The filter material is photo-definable, allowing the formation of precision pores by UV lithography. Exemplary embodiments provide a device that combines a microfilter with 3D nanotopography in culture scaffolds that mimic the 3D in vivo environment to better facilitate growth of captured cells.

Polymer microfilters, devices comprising the same, methods of manufacturing the same, and uses thereof

A microfilter comprising a polymer layer formed from epoxy-based photo-definable dry film, and a plurality of apertures each extending through the polymer layer. A method of forming a microfilter is also disclosed. The method includes providing a first layer of epoxy-based photo-definable dry film disposed on a substrate, exposing the first layer to energy through a mask to form a pattern, defined by the mask, in the first layer of dry film, forming, from the exposed first layer of dry film, a polymer layer having a plurality of apertures extending therethrough, the plurality of apertures having a distribution defined by the pattern, and removing the polymer layer from the substrate.

Polymer microfilters and methods of manufacturing the same

A new sensitive cell biomarker of solid tumors is identified in blood. This biomarker can be used to determine presence of solid tumors, rapid determination of treatment response, early detection of cancer, early detection of cancer recurrence, and may be used to determine therapy.

Capture, identification and use of a new biomarker of solid tumors in body fluids

A new sensitive cell biomarker of solid tumors and viral infection is identified in blood. This biomarker can be used to determine presence of carcinomas, sarcomas, and viruses, rapid determination of treatment response, early detection of cancer, early detection of cancer recurrence, and may be used to determine therapy.

Use of circulating cell biomarkers in the blood for detection and diagnosis of diseases and methods of isolating them

A preservative reagent for urine is disclosed that increases the stability of cells, such as tumor cells, in urine for a period of several weeks. The preservative reagent comprises polyethylene glycol (PEG), ethanol, paraformaldehyde (PFA), and ethylenediaminetetraacetic acid (EDTA), and optionally pH stabilizing reagents.

Urine preservative reagent for microfiltration

A new sensitive cell biomarker of solid tumors is identified in blood. This biomarker can be used to determine presence of carcinomas, rapid determination of treatment response, early detection of cancer, early detection of cancer recurrence, and may be used to determine therapy.

Micro- and nanofilters with precision pore sizes and pore layout have applications in many fields including capturing circulating tumor cells and fetal cells in blood, water treatment, pathogen detection in water, etc. Methods to fabricate micro- and nanofilters not using track etching or reactive ion etching are provided, allowing easy fabrication of single layer or stack of films simultaneously, and/or stack of films on rolls. Microfilter can be made using one or more layers of material. Invention enables mass production of microfilters with lithographic quality at low cost. Isolation, enumeration and characterization of circulating tumor cells using microfilters provides (i) guides to cancer treatment selection and personalize dosage, (ii) low cost monitoring for treatment response, disease progression and recurrence, (iii) assessment of pharmacodynamic effects, (iv) information on mechanisms of resistance to therapy, and (v) cancer staging. Microfabrication methods are also applicable to fabrication of any free standing patterned polymeric films.

Fabrication of microfilters and nanofilters and their applications

A microfilter comprising a polymer layer formed from epoxy-based photo-definable dry film, and a plurality of apertures each extending through the polymer layer. A microfilter comprising two or more polymer layers formed from epoxy-based photo-definable dry film, and a plurality of apertures or open areas each extending through the polymer layer. A method of forming a microfilter is also disclosed. The method includes providing a first layer of epoxy-based photo-definable dry film disposed on a substrate, exposing the first layer to energy through a mask to form a pattern, defined by the mask, in the first layer of dry film, forming, from the exposed first layer of dry film, a polymer layer having a plurality of apertures extending therethrough, the plurality of apertures having a distribution defined by the pattern, and removing the polymer layer from the substrate. Unique filter holder designs and methods appropriate to hold microfilters to collect the rare cells and allow performing assays in the filter holder are provided. The invention also describes the use of the microfilter and filter holder to collect rare cells from body fluids and perform assays. Rare cells collected on the microfilter in accordance with embodiments of the present invention can be used for medical and biological research applications.

Polymer microfiltration devices, methods of manufacturing the same and the uses of the microfiltration devices

A method of detecting fluorescence/absorbance/luminescence from 24-well, 48-well, 96-well, 384-well and 1536-well microplates and other sample containers. The sample is pumped into a waveguide. The waveguide efficiently gathers and guides the emission light to the end of the waveguide. The emission light exits the ends of the waveguide and is focused into a detector. To minimize background caused by the excitation light used for fluorescence, the excitation illuminates the waveguides at 90 degrees. To facilitate reuse, the waveguide assembly can be configured to be washed by an appropriate wash solution.

Sensitive emission light gathering and flow through detection system

Grids and collimators, for use with electromagnetic energy emitting devices, include at least a metal layer that is formed, for example, by electroplating/electroforming or casting. The metal layer includes top and bottom surfaces, and a plurality of solid integrated walls. Each of the solid integrated walls extends from the top to bottom surface and has a plurality of side surfaces. The side surfaces of the solid integrated walls are arranged to define a plurality of openings extending entirely through the layer. At least some of the walls also can include projections extending into the respective openings formed by the walls. The projections can be of various shapes and sizes, and are arranged so that a total amount of wall material intersected by a line propagating in a direction along an edge of the grid is substantially the same as another total amount of wall material intersected by another line propagating in another direction substantially parallel to the edge of the grid at any distance from the edge. Methods to fabricate these grids using copper, lead, nickel, gold, any other electroplating/electroforming materials, metal composites or low melting temperature metals are described.

Growing community of inventors

Potomac, MD, United States of America

Cha-Mei Tang