An integrated chip for rapid, sensitive, and multiplexed detection of cardiac biomarkers from fingerprick blood.

Cardiovascular diseases are the major cause of death among adults worldwide. Electrocardiogram (ECG) is a first test when a patient suffering from chest pain sees a doctor, however, it is lack of the required sensitivity. Standard assays to detect cardiac biomarkers, like enzyme-linked immunosorbent assay (ELISA) are sensitive, but suffer from important sample and reagent consumption in large-scale studies. Moreover they are performed in central laboratories of clinics and hospitals and take a long time, which is highly incompatible with the quick decisions needed to save a heart attack patient. Herein, we describe an integrated chip allowing rapid, sensitive, and simultaneous analysis of three cardiac biomarkers in fingerprick blood. The integrated chip is composed of a filtration chip for plasma separation from blood and a silicon nanowire (SiNW) array sensor chip for protein detection. These two chips are fabricated separately and bonded to form a single unit after alignment. The integrated chip is capable of reducing the dead volume of the sample by eliminating the tubing between the two chips. After the plasma is filtrated by the filtration chip, the SiNW sensor, spotted with three different antibodies, enabled us to detect three cardiac biomarkers, troponin T (cTnT), creatine kinase MM (CK-MM) and creatine kinase MB (CK-MB), simultaneously. The integrated chip is able to attain a low detection limit of 1 pg/ml for the three cardiac biomarkers from 2 µl blood in 45 min.

Multiplexed detection and differentiation of the DNA strains for influenza A (H1N1 2009) using a silicon-based microfluidic system.

Pandemic influenza by the swine-origin influenza virus (H1N1 2009) has attracted considerable concern worldwide. A convenient and accurate diagnostic approach that can be deployed at the point of care, such as in a doctor's office or at an airport, is critical for disease control. Here we report the development of a silicon-based microfluidic system for subtype differentiation of the novel H1N1 2009 strain vs. the seasonal influenza A (FluA) strain. The proposed system included two functional modules: a multiplexed PCR module for amplification of nucleic acid targets and a multiplexed silicon nanowire (SiNW) module for sequence determination. The PCR module consisted of a microfluidic PCR chamber and an electrical controller to perform a multiplexed protocol that simultaneously enriched specific segments of both H1N1 and FluA strains (if present), with 10(4)-10(5) amplification efficiency. The PCR amplicon was subsequently denatured and transferred to the SiNW sensing module for a label-free, multiplexed detection. A control SiNW was implemented, for the first time, in order to eliminate background interference. The detection module demonstrated a 10× change in the magnitude of differential current when the target DNA was injected. Overall, the system achieved a sensitivity of 20-30 fg/µl for H1N1 and seasonal FluA nucleic acids in a 10 µl sample. The low sample consumption, high sensitivity and high specificity render it a potential point-of-care (POC) platform to help doctors reach a yes/no decision for infectious diseases.

A 64-channel readout ASIC for nanowire biosensor array with electrical calibration scheme.

A 1.8-mW, 18.5-mm(2) 64-channel current readout ASIC was implemented in 0.18-µm CMOS together with a new calibration scheme for silicon nanowire biosensor arrays. The ASIC consists of 64 channels of dedicated readout and conditioning circuits which incorporate correlated double sampling scheme to reduce the effect of 1/f noise and offset from the analog front-end. The ASIC provides a 10-bit digital output with a sampling rate of 300 S/s whilst achieving a minimum resolution of 7 pA(rms). A new electrical calibration method was introduced to mitigate the issue of large variations in the nano-scale sensor device parameters and optimize the sensor sensitivity. The experimental results show that the proposed calibration technique improved the sensitivity by 2 to 10 times and reduced the variation between dataset by 9 times.

Oxygen plasma treatment for reducing hydrophobicity of a sealed polydimethylsiloxane microchannel.

Rapid prototyping of polydimethylsiloxane (PDMS) is often used to build microfluidic devices. However, the inherent hydrophobic nature of the material limits the use of PDMS in many applications. While different methods have been developed to transform the hydrophobic PDMS surface to a hydrophilic surface, the actual implementation proved to be time consuming due to differences in equipment and the need for characterization. This paper reports a simple and easy protocol combining a second extended oxygen plasma treatments and proper storage to produce usable hydrophilic PDMS devices. The results show that at a plasma power of 70 W, an extended treatment of over 5 min would allow the PDMS surface to remain hydrophilic for more than 6 h. Storing the treated PDMS devices in de-ionized water would allow them to maintain their hydrophilicity for weeks. Atomic force microscopy analysis shows that a longer oxygen plasma time produces a smoother surface.

Plasma separation from blood: the 'lab-on-a-chip' approach.

Component analysis of blood is a key diagnostic step in the detection of diseases. The separation of plasma from blood cells is therefore critical for the accuracy of diagnostic tests because cellular fractions can create discrepancies in analysis. The conventional method for separating the cellular fraction from whole blood is by centrifugation, which requires a laboratory infrastructure. In the last decade, intensive research to scale down experimental processes has seen unprecedented advances in microfabrication and related techniques that have led to utilization of the micro-level phenomenon to accomplish a myriad of physicochemical separation processes. Salient features of these devices include small sample size, faster reaction times, precise control of reaction environments, and affordability. Various plasma-separation devices have also been designed based on microfluidic platforms. The challenges associated with these devices are manifold: particle clogging, necessity for sample preparation, flow-rate maintenance, low reproducibility, and optimization of output. Further, quality, reliability, and consistency remain a huge issue with micromedical devices. The present article reviews current developments in the field of plasma separation from blood implementing innovative microtechnologies to achieve high-throughput plasma separation.