Lens-Free, High-Throughput Imaging Developed for Cell Phones

The distance between people in many Third World and developing countries in need of healthcare and the facilities capable of providing it constitutes a major hurdle to improving healthcare. One solution involves devising medical diagnostic applications small enough to fit into objects already in common use, such as cell phones--in effect, bringing the hospital to the patient.

Researchers from the University of California, Los Angeles (UCLA) have developed an innovative lens-free, high-throughput imaging technique for potential use in such medical diagnostics, which has the potential to improve global disease monitoring, particularly in resource-limited environments such as in Africa. The research, which was published in September 2008 in the journal Cellular and Molecular Bioengineering (CMBE), outlined improvements to a technique known as LUCAS (lensless ultra-wide-field cell monitoring array platform based on shadow imaging).

First published in the Royal Society of Chemistry's journal Lab Chip in 2007, the LUCAS technique, developed by UCLA researchers, demonstrated a lens-free technique for rapidly and accurately counting targeted cell types in a homogenous cell solution. Removing the lens from the imaging process allows LUCAS to be scaled down to the point that it can eventually be incorporated into a regular wireless cell phone. Samples could be loaded into a specially equipped phone using a disposable microfluidic chip.

The UCLA researchers have now improved the LUCAS technique to the point that it can categorize a significantly larger sample volume than previously shown--up to 5 ml, from an earlier volume of less than 0.1 ml--representing a key step toward portable medical diagnostic applications.

The research team was led by Dr. Aydogan Ozcan, assistant professor of electrical engineering at the UCLA Henry Samueli School of Engineering and Applied Science. Dr. Ozcan envisions individuals one day being able to draw a blood sample into a chip the size of a U.S. quarter, which could then be inserted into a LUCAS-equipped cell phone that would quickly identify and count the cells within the sample. The read-out could be sent wirelessly to a hospital for further analysis. "This on-chip imaging platform may have a significant impact, especially for medical diagnostic applications related to global health problems such as HIV or malaria monitoring,” Dr. Ozcan said.

LUCAS functions as an imaging strategy in which the shadow of each cell in an entire sample volume is detected in less than a second. The acquired shadow image is then digitally processed using a custom-developed "decision algorithm” to enable both the identification of the cell/bacteria location in three-dimensional (3D) and the classification of each microparticle type within the sample volume.

Various cell types--such as red blood cells, fibroblasts, and hepatocytes--or other microparticles, such as bacteria, all exhibit uniquely different shadow patterns and therefore can be rapidly identified using the decision algorithm.

The new study demonstrates that the use of narrowband, short-wavelength illumination significantly improves the detection of cell shadow images. Furthermore, by varying the wavelength, the two-dimensional pattern of the recorded cell signatures can be tuned to enable automated identification and counting of a target cell type within a mixed cell solution. "This is the first demonstration of automated, lens-free counting and characterization of a mixed, or heterogeneous, cell solution on a chip and holds significant promise for telemedicine applications,” Dr. Ozcan said.

Another improvement detailed in the UCLA research is the creation of a hybrid imaging scheme that combines two different wavelengths to further improve the digital quality of shadow images. This new cell classification scheme has been termed "multicolor LUCAS.” As the team demonstrated, additional improvement in image quality can also be achieved using adaptive digital filtering. As result of these upgrades, the volume of the sample solution that can be imaged has been increased, as mentioned, from less than 0.1-5 ml.

"This is a significant advance in the quest to bring advanced medical care to all reaches of the planet,” said Dr. Leonard H. Rome, senior associate dean for research at the David Geffen School of Medicine at UCLA. "The implications for medical diagnostic applications are in keeping with CNSI [California NanoSystems Institute at UCLA] initiatives for new advances toward improving global health.”

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