Quantitative detection of bioassays with a low-cost image-sensor array for integrated microsystems.

A considerable global need exists for simple, portable, inexpensive, and integrated assay and diagnostic approaches that are appropriate for use in minimal-infrastructure, resource-poor settings, such as those found in the developing world, as well as in resource-limited environments, such as those encountered by emergency first responders, primarycare physicians, patients at home, forensic investigators, and military field personnel. Continuing advances in microfluidics have enabled the demonstration of prototype lab-ona-chip devices that offer to help answer this challenge and improve access to chemical and biological sample analysis by paving the way for the introduction of low-cost, portable point-of-need assay systems. Although such systems would have immediate applications in many fields, there are at present relatively few commercially available examples of the technology. 5] In clinical and industrial laboratory analyses, the most widely used and generally accepted methods to quantify particulate chemical or biochemical analytes employ optical detection approaches based on absorbance, fluorescence, or luminescence. Although lab-on-a-chip implementations of optical methods have been demonstrated, detection is typically carried out off-chip by using conventional microscope optics and digital-camera systems or custom and relatively expensive chip-scale optoelectronics. 7] The translation of these established methods into truly portable total-analysis microsystems has been hindered in part by a lack of reasonably priced, sensitive, and compact optical detectors that can be interfaced readily with microfluidic sample handling. In response to this limitation, we demonstrate the feasibility of applying an inexpensive, readily available complementary metal–oxide–semiconductor (CMOS) image sensor, originally intended for use in mass-market digitalcamera applications, for integrated optical detection in a variety of microfluidic systems. Specifically, we report the direct integration of this chip-scale sensor with our digital fluid-handling system to track nanoliter-volume reagent droplets by contact imaging. We also show the more general application of the sensor as a quantitative photometer for the integrated optical detection of colorimetric and bioluminescence assays implemented in various lab-on-a-chip architectures. Point-of-need assay platforms will complement, rather than supplant, existing laboratory-based analysis methods and hardware that form the foundation of clinical diagnostics and academic research. Indeed, within the realm of analytical (and in particular, diagnostic) technology and instrumentation, the development of inexpensive point-of-need assays is a rather specific, but not inconsequential endeavor. Over 95% of deaths due to major infectious diseases occur in developing countries. Although these diseases are largely treatable with drug therapy, the lack of available, infrastructure-appropriate diagnostic assays means that healthcare workers in these settings are unable to identify who is, or—just as critically—is not, in need of treatment. Simple, portable, inexpensive assay systems are also of value in natural-disaster and other emergency situations that arise indiscriminately in all countries. Technology and instrumentation for performing chemical and biochemical analyses have, thus far, typically been advanced to meet the demands of comparatively wellfunded laboratories. State-of-the-art assay systems employing flow-injection analysis (FIA), automated microplate processors and readers, or other mechanized sample-handling technologies, 12] provide impressive capabilities for continuous or parallel processing and the assaying of hundreds or thousands of samples per hour (sample preparation and readout times combined can average well under one second per sample). Thus, they are especially useful in centralized laboratories where high-throughput is essential. Whereas such systems are currently the mainstay of clinical diagnostics, drug discovery, and many research laboratories (and will probably remain so for the foreseeable future), the primary target of lab-on-a-chip assay approaches is to provide “sample in, answer out” assay capabilities by integrating sample handling and processing steps into a closed microfluidic, often single-use, architecture that is more ideally suited for localized assay applications. It is probable that many analyses will remain the province of dedicated centralized laboratories, but it is also anticipated that therapies and biomarkers discovered with high-through[*] Dr. D. M. Vykoukal, Dr. G. P. Stone, Dr. P. R. C. Gascoyne, Dr. E. U. Alt, Dr. J. Vykoukal Department of Molecular Pathology, The University of Texas M. D. Anderson Cancer Center 7435 Fannin Street, Houston, TX 77054 (USA) Fax: (+ 1)713-834-6103 E-mail: jody@mdanderson.org