Blood Plasma Separation in Microfluidic Channels Using Flow Rate Control SUNG YANG,*AKIF ÜNDAR,† JEFFREY D. ZAHN* Several studies have clearly shown that cardiac surgery in- duces systemic inflammatory responses, particularly when cardiopulmonary bypass (CPB) is used. CPB induces complex inflammatory responses. Considerable evidence suggests that systemic inflammation causes many postoperative complica- tions. Currently, there is no effective method to prevent this systemic inflammatory response syndrome in patients under- going CPB. The ability to clinically intervene in inflammation, or even study the inflammatory response to CPB, is limited by the lack of timely measurements of inflammatory responses. In this study, a microfluidic device for continuous, real-time blood plasma separation, which may be integrated with downstream plasma analysis device, is introduced. This de- vice is designed to have a whole blood inlet, a purified plasma outlet, and a concentrated blood cell outlet. The device is designed to separate plasma with up to 45% hematocrit of the inlet blood and is analyzed using computational fluid dynamics simulation. The simulation results show that 27% and 25% of plasma can be collected from the total inlet blood volume for 45% and 39% hematocrit, respectively. The de- vice’s functionality was demonstrated using defibrinated sheep blood (hematocrit  39%). During the experiment, all the blood cells traveled through the device toward the con- centrated blood outlet while only the plasma flowed towards the plasma outlet without any clogging or lysis of cells. Be- cause of its simple structure and control mechanism, this microdevice is expected to be used for highly efficient, real- time, continuous cell-free plasma separation. ASAIO Journal 2005; 51:585–590. M icrofluidic platforms have the great potential to change the way medicine and biology is conducted in hospitals and lab- oratories. Such platforms have attracted considerable research interest due to the opportunity to fabricate a highly integrated system that is able to perform parallel sample handling and analysis on a single chip (i.e., lab-on-a-chip). Although mi- crofluidics promises to have an impact in many research fields, one of the more attractive applications of microfluidics has been toward biomedical and life science diagnostics. 1–3 Mi- crofluidic devices are attractive because they offer many ad- vantages such as smaller reagent volume consumption, shorter reaction times, and the possibility of parallel operation. These advantages result not only in time and cost savings for diag- nostic tests, but can also be life-saving in time-critical environ- ments such as critical medical diagnostics. For instance, when performing blood analysis in medical laboratories, the blood cells are separated from whole blood by centrifugation, and plasma is analyzed for electrolyte concentration, glucose, lac- tate, and total cholesterol, among other parameters. These sequential procedures can take up to several hours. However, there is a need for a system that can separate blood plasma from whole blood and measure the concentration of the clin- ically relevant proteins in real time. For example, several studies have clearly shown that cardiac surgery induces sys- temic inflammatory responses, particularly when cardiopul- monary bypass (CPB) is used. 4 –13 These systemic responses are attributed to several factors, including exposure of blood to nonphysiologic surfaces of the heart-lung circuit, ischemia- reperfusion of the involved tissues, surgical trauma, and hypo- thermia. 4,13,14 Currently, there is no effective method to pre- vent this systemic inflammatory response syndrome in patients undergoing CPB. The ability to clinically intervene in inflam- mation, or even study the inflammatory response to CPB, is limited by the lack of timely measurements of inflammatory responses. Current technology provides measurements of the effects of CPB on activation of complements, neutrophils, platelets, and cytokines hours or days after surgery. However, more immediate measurements would help us to understand the mechanisms of cellular activation, and to modify surgical and perfusion protocols that would minimize the adverse ef- fects of CPB. Currently, there are several reports related to blood-handling microdevices. 15,16 In this study, a microfluidic device for continuous, real-time blood plasma separation, which may be integrated with a downstream plasma analysis device, is presented. The device is made out of polydimethyl- siloxane (PDMS), which is considered to be a hemocompatible material. Even though no truly hemocompatible biomaterial has yet been found, PDMS is assumed to be a suitable bioma- terial for the experimental devices because it causes minimal endotoxin contamination, leukocyte activation, and comple- ment activation. 17,18 It is also assumed that the activation of inflammatory responses caused by the PDMS (foreign surface) itself can be ignored when the blood exposure time to PDMS is short (i.e., seconds). Principle of the Blood Plasma Separation Microdevice The principle of the plasma separation device is based on the bifurcation law, 19,20 also called the Zweifach-Fung effect. The bifurcation law describes that, in the microcirculation, when From the *Department of Bioengineering, Pennsylvania State Uni- versity, University Park, PA; and †Departments of Pediatrics, Surgery, and Bioengineering, Pennsylvania State University, College of Medi- cine, Penn State Children’s Hospital, Hershey, PA. Submitted for consideration April 2005; accepted in revised form July 2005.Presented in part at the First International Conference on Pediatric Mechanical Circulatory Support Systems and Pediatric Car- diopulmonary Perfusion, May 19 –22, Hershey, PA, USA. DOI: 10.1097/01.mat.0000178962.69695.b0 ASAIO Journal 2005 585