SBIR-STTR Award

We propose to develop a dynamic quantitative phase-imaging interference 4D microscope system operating in reflection to enable creating phase image movies and quantifying motion of live cells and cellular processes in vitro without the need for adding contrast agents, ultimately having application to clinical measurements in vivo. The primary use of this microscope is to study the structure and mechanics of cells, cellular processes and tissues. This interference microscope will enable looking at cellular morphology, cellular development and structures within cells and tissues over periods of time. It is intended to have a flexible design that enables options of different magnifications, resolutions, and wavelengths. The Phase I project focuses on development of a dynamic polarization Michelson interference microscope with a 10-20X objective providing an optical resolution of 2.0 5m. Polarization states will be used to differentiate object and reference beams. Technology originally developed for dynamically measuring the seeing quality of large telescopes in situ will be utilized for imaging on the microscopic level. This technology utilizes a pixilated single-shot phase-measurement camera to enable instantaneous quantitative determination of optical phase and refractive index variations in real time to create movies of dynamic motions. Goals for Phase I include design of a modular polarization microscope and Michelson interferometer with the integrated pixilated phase-measurement camera, development of basic software algorithms to extract and create topographic and optical thickness movies of biological objects, testing the optical performance of the system and demonstrating dynamic 4D measurements on a number of in vitro cell cultures.

Public Health Relevance:
This dynamic quantitative phase-imaging technology implemented within an interferometric microscope system represents a key element in advancing the ability to image tissues, cells, and cellular components in real-time without the need for toxic contrasts agents to observe the motion and growth of cells in living biological objects, and discern differences between types of cells. This instrument will create dynamic 4D phase image movies of cellular events for studying in vitro cellular structure and morphology, motion, motility and mechanics.

Public Health Relevance Statement:


Project narrative:
This dynamic quantitative phase-imaging technology implemented within an interferometric microscope system represents a key element in advancing the ability to image tissues, cells, and cellular components in real-time without the need for toxic contrasts agents to observe the motion and growth of cells in living biological objects, and discern differences between types of cells. This instrument will create dynamic 4D phase image movies of cellular events for studying in vitro cellular structure and morphology, motion, motility and mechanics.

Project Terms:
4-dimensional; Algorithms; Analysis, Data; Area; Biological; Body Tissues; Cell Components; Cell Culture Techniques; Cell Function; Cell Locomotion; Cell Migration; Cell Movement; Cell Process; Cell Structure; Cell physiology; Cells; Cellular Expansion; Cellular Function; Cellular Growth; Cellular Migration; Cellular Morphology; Cellular Physiology; Cellular Process; Cellular Structures; Clinical; Complex; Computer Programs; Computer software; Contrast Agent; Contrast Drugs; Contrast Media; Data; Data Analyses; Data Quality; Dental; Dental Enamel; Detection; Development; Device or Instrument Development; Diagnosis; Dimensions; Electronics; Elements; Enamel; Endoscopes; Engineering; Engineerings; Ensure; Environment; Evaluation; Event; Four-dimensional; Freedom; Frequencies (time pattern); Frequency; Future; Goals; Government; Head; Height; Holography; Illumination; Image; Imagery; Imaging technology; In Situ; In Vitro; In element; Indium; Interferometry; Label; Laboratory Research; Legal patent; Length; Liberty; Life; Light; Lighting; Magnetism; Masks; Measurement; Measures; Mechanics; Methods; Methods and Techniques; Methods, Other; Microscope; Microscopic; Microscopy; Modality; Morphology; Motility; Motility, Cellular; Motion; Operating System; Optics; Patents; Pattern; Performance; Persons; Phase; Photoradiation; Property; Property, LOINC Axis 2; Quality, Data; Radiopaque Media; Refractive Indices; Research; Research Specimen; Research, Laboratory; Resolution; Rotation; Sampling; Scanning; Side; Software; Source; Specimen; Structure; Structure of nail of toe; Subcellular Process; Surface; System; System, LOINC Axis 4; Techniques; Technology; Testing; Thick; Thickness; Time; Tissues; Toe Nail; Toenail; Variant; Variation; Vibration; Vibration - physical agent; Visualization; Work; base; cell growth; cell morphology; cell motility; cell type; cellular development; computer program/software; cost; demineralization; design; designing; device development; digital; experience; flexibility; fungus; imaging; in vivo; innovate; innovation; innovative; instrument; instrument development; lithography; magnetic; millimeter; movie; novel; prototype; public health relevance; reconstruction; sensor; tissue culture; tool; tooth enamel; vibration

This project will develop a dynamic quantitative phase-imaging interference 4D microscope system to enable creating phase image movies and quantifying motion of live cells and cellular processes in vitro using harmless light levels without the need for adding contrast or labeling agents. The primary use of this microscope is to study the structure and mechanics of cells, cellular processes and tissues. This interference microscope will enable looking at cellular morphology, cellular development and structures within cells and tissues over periods of time. It is intended to have a flexible design that enables options of different magnifications, resolutions, and wavelengths. The Phase II project focuses on developing a production prototype for a commercial dynamic phase imaging interference microscope system using interchangeable interference objectives and low coherence sources with fiber delivery. Polarization states will be used to differentiate object and reference beams. Technology originally developed for dynamically measuring the seeing quality of large telescopes in situ will be utilized for imaging on the microscopic level. This technology utilizes a pixilated single-shot phase-measurement camera to enable instantaneous quantitative determination of optical phase and refractive index variations in real time to create movies of dynamic motions. Goals for Phase II include 1) designing, building and testing a production prototype microscope system with multiple magnifications, 2) development of software and algorithms to display optical thickness data in real time relative to a background surface and capture bursts of data to quantify cellular motion, morphology and volume, 3) demonstrating quantitative measurements on dynamic living cells at multiple beta sites with research partners, and to obtain written user feedback for implementation in Phase III.

Public Health Relevance:
This dynamic quantitative phase-imaging technology implemented within an interferometric microscope system represents a key element in advancing the ability to rapidly image tissues, cells, and cellular components in real-time without the need for toxic contrasts agents using harmless light levels to observe cellular processes in living biological objects, and track changes among and within cells. This instrument will create dynamic 4D phase image movies of cellular events for studying in vitro cellular structure and morphology, motion, motility and mechanics.

Thesaurus Terms:
Algorithms;Arizona;Biological;Body Tissues;Breast Cancer Cell;Buffers;Cancer Center;Cell Components;Cell Culture Techniques;Cell Function;Cell Locomotion;Cell Migration;Cell Movement;Cell Nucleus;Cell Process;Cell Structure;Cell Physiology;Cells;Cellular Function;Cellular Migration;Cellular Morphology;Cellular Physiology;Cellular Process;Cellular Structures;Computer Programs;Computer Software;Contrast Agent;Contrast Drugs;Contrast Media;Data;Ensure;Environment;Event;Feedback;Fiber;Glass;Goals;Human Breast Cancer Cell;Image;Imaging Technology;In Situ;In Vitro;In Element;Indium;Label;Laboratory Research;Legal Patent;Life;Light;Marketing;Masks;Measurement;Measures;Mechanics;Methods;Microscope;Microscopic;Morphology;Motility;Motility, Cellular;Motion;Msec;Nucleus;Optics;Patents;Performance;Phase;Photochemotherapy;Photodynamic Therapy;Photoradiation;Production;Quantitative Evaluations;Radiopaque Media;Refractive Indices;Relative;Relative (Related Person);Research;Resolution;Sample Size;Sampling;Scanning;Site;Software;Source;Staining And Labeling;Structure;Subcellular Process;Surface;System;System, Loinc Axis 4;Technology;Testing;Thick;Thickness;Time;Tissues;Universities;Variant;Variation;Vibration;Vibration - Physical Agent;Writing;Base;Cell Morphology;Cell Motility;Cellular Development;Computer Program /Software;Computer Program/Software;Computerized Data Processing;Cost;Data Processing;Design;Designing;Develop Software;Developing Computer Software;Flexibility;Imaging;Improved;Instrument;Meetings;Migration;Millisecond;Movie;Neoplasm /Cancer Photoradiation Therapy;Neoplasm/Cancer Photoradiation Therapy;Processing Speed;Prototype;Signal Processing;Software Development;Tool;University;Usability;Vibration