Point-of-Care Systems for Cellular Analysis

Abstract

Cellular analysis is a vital part of diagnostics testing for most diseases. The development of modern technologies has led to great advancement in this task. However, the use of cellular analysis systems is limited mainly to laboratories and clinics due to their high cost and large size. Providing affordable and accessible diagnostic testing to the majority of population in the developing world and resources-limited regions remains a technical challenge. To overcome this challenge, cost-effective and portable point-of-care (POC) systems have emerged in recent years as a priming approach. This thesis focuses on the development of such POC systems for the purpose of cellular analysis. These systems include sub-pixel resolution holographic imager for cellular profiling and microfluidic platforms for sorting cell populations in clinical samples and capturing single cells. First, a new lens-free holographic system is reported as a portable imaging tool for fast screening and profiling of individual cells. Compared to conventional microscopy, this system is cheaper in cost, and portable; it can provide fast automatic detection over a large field-of-view and profile cells for in terms of their molecular properties. To enhance the resolution of the lens-free holographic system, a novel sub-pixel resolution enhancement method has been developed. Typical lens-free holographic systems are limited in resolution by the pixel size of their inherent image sensors. The developed method can overcome this limitation by applying compressive sensing strategy to the reconstruction process. Compared to other resolution enhancement methods for lens-free holography, this method does not require additional hardware or multiple exposures in measurement, thus provides the potential for fast imaging of sub-pixel targets. It can also be further applied to other nonlinear holographic imaging systems. In addition to cell imaging, novel microfluidic platforms were also developed to address the challenges in separating and capturing scant cells in blood or other fluid samples from patients. A single-cell capturing system is developed for the detection of lymphoma from cerebral spinal fluid (CSF) samples. Compared to existing single-cell capturing systems, this chip offers the advantage of antibody-free trapping mechanism, large number of sites for high throughput screening, and special geometry that size-selectively captures lymphoid cells. Blood sample usually contains a variety of cell populations which makes it difficult to sort low abundant cell for clinical diagnosis. To achieve high efficiency separation of cell populations in blood stream, a hybrid magnetic-microfluidic cell sorting system was developed. Compared with previous work, the new system achieved higher separation efficiency without damaging target cells; it is also easier to assemble and thus eliminates additional training needed for device operation. These POC systems provide versatile approach for fast, cheap and accurate disease diagnosis. With further customization specific to the diseases and more clinical testing, they can be applied as powerful tools for more accessible healthcare in low-income and resources limited regions.