A high-efficiency superhydrophobic plasma separator

Abstract

To meet stringent limit-of-detection specifications for low abundance target molecules, a relatively large volume of plasma is needed for many blood-based clinical diagnostics. Conventional centrifugation methods for plasma separation are not suitable for on-site testing or bedside diagnostics. Here, we report a simple, yet high-efficiency, clamshell-style, superhydrophobic plasma separator that is capable of separating a relatively large volume of plasma from several hundred microliters of whole blood (finger-prick blood volume). The plasma separator consists of a superhydrophobic top cover with a separation membrane and a superhydrophobic bottom substrate. Unlike previously reported membrane-based plasma separators, the separation membrane in our device is positioned at the top of the sandwiched whole blood film to increase the membrane separation capacity and plasma yield. In addition, the device’s superhydrophobic characteristics (i) facilitates the formation of well-defined, contracted, thin blood film with a high contact angle; (ii) minimizes biomolecular adhesion to surfaces; (iii) increases blood clotting time; and (iv) reduces blood cell hemolysis. The device demonstrated a “blood in-plasma out” capability, consistently extracting 65±21.5 μL of plasma from 200 μL of whole blood in less than 10 min without electrical power. The device was used to separate plasma from Schistosoma mansoni genomic DNA-spiked whole blood with a recovery efficiency of > 84.5 ± 25.8 %. The S. mansoni genomic DNA in the separated plasma was successfully tested on our custom-made microfluidic chip by using loop mediated isothermal amplification (LAMP) method.

Multiplexed efficient on-chip sample preparation and sensitive amplification-free detection of Ebola virus

“…Fingerprick blood samples are easier to obtain than needle draws, can be collected from several sites on the body, and can be done with little training. Viral RNA extraction from whole blood can also be achieved on-chip by using a cell lysis reagent (Hui et al 2007) and filtering process (Liu et al 2016). In our own work, whole blood filtration and nucleic acid extraction have been demonstrated by using PDMS microfluidic devices in combination with ARROW chips for multiplex optical detection of cancer biomarkers (Cai et al 2016).…”

Microfluidic System for Detection of Viral RNA in Blood Using a Barcode Fluorescence Reporter and a Photocleavable Capture Probe

“…Although polymerase chain reaction (PCR) shows similar throughput, it often requires an off-chip plasma separation 47 and an RNA isolation step 48 before target amplification. In addition, PCR requires precise temperature control and expensive and sensitive enzymes.…”

Miniaturized devices for point of care molecular detection of HIV

“…Finger or heel-prick sampling is relatively simple, minimally invasive and more convenient [38,39], and has been validated against standard phlebotomy in HIV testing [40]. To this end, Liu et al [41] developed a superhydrophobic clamshell plasma separator (Fig. 1B) incorporating superhydrophobic coatings to reduce non-specific absorption and achieve high efficiency plasma separation.…”

“…The device is capable of extracting 65 μL of plasma from 200 μL of undiluted finger-prick blood (Maximum volume of finger-prick blood is 250–500 μL [42]). The plasma separated by the superhydrophobic separator was used for the detection of cell-free Schistosoma mansoni DNA [41] and HIV virus.…”