A microwell array cytometry system for high throughput single cell biology and bioinformatics

Recent advances in systems biology and bioinformatics have highlighted that no cell population is truly uniform and that stochastic behavior is an inherent property of many biological systems. As a result, bulk measurements can be misleading even when particular care has been taken to isolate a single cell type, and measurements averaged over multiple cell populations in a tissue can be as misleading as the average height at an elementary school. Unfortunately, there are relatively few experimental systems available at present that can provide a combination of single cell resolution, large cell populations, and the ability to track individual cells over multiple time points. Those systems that do exist are often difficult to automate and require extensive user intervention simply to generate the raw data sets for later analysis. The goal of this thesis project was to develop a powerful, inexpensive, and easy-to-use system that meets the above requirements and can serve as a platform for single cell bioinformatics. Our current system design is composed of two basic parts: 1) a customizable PDMS device consisting of one or more microwell arrays, each with associated alignment and identification features, and 2) a suite of custom software tools for automated image processing and data analysis. The system has a number of significant advantages over competing technologies such as flow cytometry and standard image cytometry. Unlike flow cytometry, the cells are not in suspension, and individual cells can be tracked across multiple time points or examined before and after a treatment.

Department dc:contributor.department

Harvard University--MIT Division of Health Sciences and Technology

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2009

Author dc:creator

• Roach, Kenneth L. (Kenneth Lee), 1979-

Advisor dc:contributor.advisor

• Mehmet Toner.

• Harvard University--MIT Division of Health Sciences and Technology.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/47850

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/47850