We describe a new optical detection technique, termed ''spatially modulated fluorescence emission,'' that delivers high signal-to-noise discrimination without precision optics to enable a flow cytometer that can combine high performance, robustness, compactness, low cost, and ease of use. The detection technique is demonstrated with measurements of absolute CD41 and percentage CD4 counts in human blood. Benchmarking against a commonly used commercial instrument for this test yields excellent agreement for both absolute CD4 and percentage CD4. ' 2011 International Society for
Advancement of CytometryKey terms flow cytometer; optofluidics; microfluidics; optical detection; CD4; AIDS diagnostics; point of care testing THE strategic landscape for biological and biomedical testing is undergoing a truly disruptive transformation. Today, the majority of tests are performed at major, centralized clinical laboratories due to the enormous costs associated with typical instruments and the high level of skill required to operate the sophisticated systems. Unfortunately, this centralization often leads to inconvenient and sometimes even unacceptably long times for notification of the results. As soon as compact, robust, fast, and inexpensive instruments for sophisticated diagnostic at point of need are available, the current health-diagnostics-delivery model will change dramatically (1). The principal drivers for this development are reducing costs, timely delivery of test results, lowering mortality rates, and reducing morbidity. Improved point-of-care (POC) diagnostics is urgently needed to enhance patient survival and recovery through rapid decision-making by doctors, nurses, and emergency response teams at the bedside in hospitals, in critical-care units, emergency rooms, community hospitals, and disaster-response sites. Another main driver for POC devices is medical diagnostics and screening for diseases in the developing world where the current health-diagnostics-delivery model established in the western world is not practical or does not exist (2). POC testing appears to be the only practical solution in this setting. Currently, the prime critical need for a POC device is a field deployable CD4 monitor for screening and treatment of HIV infections. Most CD4 tests are carried out on dedicated flow cytometers (e.g., BD FACSCount, Partec CyFlow Counter, and Guava/Merck Easy CD4), which fulfill the needs at acceptable costs as long as they can be performed in well-controlled environments by well-trained operators, but are typically not suited for routine testing in remote areas. Several alternatives to flow cytometry have been developed [e.g., LabNow (3), PIMA, Alere/Invernes (4), Daktari (5), and StarCount (6,7)] to address the need in regions without access to central laboratory testing, but none of the developed tests have yet proven to meet the challenging requirements in locations without reliable supply of electricity or clean water,