Proteins and their byproducts play a critical role in nearly every event that takes place within living cells. The understanding of many of these events is furthered by the ability to profile the concentration of specific proteins as a function of time and various physiological conditions. However, the rate at which these parameters are measured by current methodology is often limited by requirements for large sample volumes and time-consuming modifications of the molecules under investigation. Here we address these limitations by proposing a detection system based on microfluidic channels whereby the channels themselves are the detectors. The key innovation is that the mechanical properties of a suspended microfluidic channel with a thickness near a micron will allow protein concentration to be determined by measuring a mass-dependent resonant frequency of the microchannel. The suspended channel mass is altered either by proteins that enter into the channel volume, or by specific binding of proteins to capture molecules on the channel walls. Successful development of the suspended microchannel detector will result in a real-time and labelfree method that will provide an alternative to fluorescence for protein detection. Specifically, suspended microchannel detectors will offer two advances. First, is scalability: ultimately 10[2]-10[3] detectors could be operated within a square centimeter with a volume of less than 100 pL per detector. Second, we estimate that the suspended microchannel will achieve a detection limit in the range of 10[-18] is to 10[-19] g/mu m 2. This limit, which corresponds to less than 10 proteins/mu m 2, is nearly 100-fold more sensitive than other label-free methods such as the quartz crystal microbalance. We anticipate that an array of suspended microchannel detectors will substantially increase the throughput and utility of protein assays that are used for furthering the predictive power of system-level modeling. The suspended microchannels will also be useful for enabling point-of-care medical diagnostics.
| Son, Sungmin; Grover, William H; Burg, Thomas P et al. (2008) Suspended microchannel resonators for ultralow volume universal detection. Anal Chem 80:4757-60 |
