Biological fluids (such as blood, saliva, and urine) contain a large amount of information that can be used for medical diagnostic purposes. This information is encoded within biological molecules (i.e., proteins and DNA) and cells with sizes ranging from a few nanometers to ~20μm. Precise extraction and timely processing of this information can ensure efficient medical diagnosis. Traditionally, analysis of biological fluids is carried out in specialized laboratories that require highly trained personnel and access to sophisticated instruments. However, such facilities are not always available in remote areas or underdeveloped countries. Therefore, development of simple and efficient devices is needed for fundamental processing of biological fluids for medical diagnosis.
Many diseases and illnesses are characterized by abnormal variations in the amounts of molecules and cells in biological fluids. Detecting these small variations, especially during the early stages of disease progression, can be achieved by ultrahighly sensitive optical or electrochemical detection methods.1 Alternatively, less sensitive devices can be used if these biological molecules are transported and concentrated in a confined region within the fluid sample. We (as well as other colleagues) previously developed a variety of microsystems for transportation and concentration of biological molecules for disease detection.2,3 Despite the versatility of these microsystems, external power sources are required for their operation, which increases the size and weight of such systems and may limit their applicability in remote areas.
The coffee-ring phenomenon offers a novel avenue for transportation and concentration of molecules without requiring external power sources. A coffee ring forms when a liquid droplet containing suspended particles evaporates. These particles are transported to the droplet's edge by the evaporation-induced capillary flow.4 Once all liquid has evaporated, most particles are concentrated at the edge, forming a ring pattern (see Figure 1). Coffee-ring formation is a natural process that has great potential for biomolecular sensing and processing on micro- and nanoscales. However, before we can take advantage of this phenomenon on smaller length scales, its natural size limit must be understood more fully.
Figure 1. Microscale coffee ring.
To determine the size of the smallest droplet that results in a coffee ring, we manufactured a surface engineered with alternating hydrophilic and hydrophobic regions.5 We then washed the surface with a water-based solution containing latex particles of 20 to 100nm in size (similar to the biological molecules of interest). We placed water droplets on the hydrophilic regions and coffee rings formed upon evaporation. We repeated the experiments with smaller hydrophilic patterns until the coffee-ring phenomenon was no longer evident (see Figure 2).
Figure 2. Coffee-ring formation for decreasing droplet sizes.
We showed that droplets containing 100nm-sized particles can produce well-defined coffee rings down to 10μm in circumference, which is 10 times smaller than the width of a single human hair. For smaller droplets, water evaporates faster than the particles can move: rather than forming a ring pattern, the particles will be dispersed uniformly within the droplet region, since they do not have enough time to move to the droplet's edges.6 Physical understanding of coffee-ring formation on small scales will guide us to design engineering devices for effective biomolecular transportation and concentration.
Thus far, we have shown that the coffee-ring phenomenon can be used as a simple yet effective mechanism for particle transportation and concentration on small scales. Now that we better understand the definitive size limit of coffee-ring formation, we are exploring the capabilities of these microscale coffee rings for novel biomolecular-processing devices. We believe that coffee-ring-based bioprocessing techniques, when integrated with suitable protocols for detection of disease-specific biological markers, can offer a novel, simple, and low-cost solution for biodetection and diagnostic testing in remote areas and underdeveloped countries.
This research is funded by the Center for Cell Control through the National Institutes of Health's Roadmap for Nanomedicine and by the Center for Scalable and Integrated Nanomanufacturing through the National Science Foundation.
University of California at Los Angeles (UCLA)
Los Angeles, CA
Chih-Ming Ho is the Ben Rich-Lockheed Martin professor. He is a member of the National Academy of Engineering and the Academia Sinica, as well as an elected fellow of the American Physical Society and the American Institute of Aeronautics and Astronautics for his contributions in bio-nanotechnology, micro/nanofluidics, and turbulence.
Mechanical and Aerospace Engineering, UCLA
Los Angeles, CA
Tak-Sing Wong is a postdoctoral research scholar. He received his PhD from UCLA under the guidance of Chih-Ming Ho. His work focuses on micro/nanomanufacturing science and technology for advanced materials and biomedical applications.
Institute of Microelectronics
Xiaoying Shen is an undergraduate student majoring in electronics engineering. She was an exchange research student at UCLA under the guidance of Chih-Ming Ho. Her research interests include micro- and nanotechnology for bio-inspired applications. She will pursue a PhD degree at Stanford University from 2010.