Erhan Ermek

Microcantilever based disposable viscosity sensor for serum and blood plasma measurements

This paper proposes a novel method for measuring blood plasma and serum viscosity with a microcantilever-based MEMS sensor. MEMS cantilevers are made of electroplated nickel and actuated remotely with magnetic field using an electro-coil. Real-time monitoring of cantilever resonant frequency is performed remotely using diffraction gratings fabricated at the tip of the dynamic cantilevers. Only few nanometer cantilever deflection is sufficient due to interferometric sensitivity of the readout. The resonant frequency of the cantilever is tracked with a phase lock loop (PLL) control circuit. The viscosities of liquid samples are obtained through the measurement of the cantilevers frequency change with respect to a reference measurement taken within a liquid of known viscosity. We performed measurements with glycerol solutions at different temperatures and validated the repeatability of the system by comparing with a reference commercial viscometer. Experimental results are compared with the theoretical predictions based on Saders theory and agreed reasonably well. Afterwards viscosities of different Fetal Bovine Serum and Bovine Serum Albumin mixtures are measured both at 23°C and 37°C, body temperature. Finally the viscosities of human blood plasma samples taken from healthy donors are measured. The proposed method is capable of measuring viscosities from 0.86 cP to 3.02 cP, which covers human blood plasma viscosity range, with a resolution better than 0.04 cP. The sample volume requirement is less than 150 μl and can be reduced significantly with optimized cartridge design. Both the actuation and sensing are carried out remotely, which allows for disposable sensor cartridges.

Simultaneous self-sustained actuation and parallel readout with MEMS cantilever sensor array

Parallel readout of a microcantilever array using single magnetic actuator and a single photo detector for concurrent detection is reported. The system includes MEMS cantilever array designed for different resonance frequencies, optical elements for laser beam shaping and focusing, one detector and feedback electronics, and single broadband actuator for parallel excitation. The cantilevers are made using a simple one-mask fabrication process with embedded amplitude gratings at the tips. A line shaped laser beam is used to illuminate the cantilevers. A single readout photodiode is placed at the first order diffraction beam location on the Fourier plane. The amplified photodiode signal is fed back into the magnetic actuation using a preamplifier and a broadband current amplifier. In this paper, we report for the first time parallel monitoring of the thermal resonance peaks of inherently frequency-multiplexed MEMS cantilevers. We demonstrated simultaneous self-sustained oscillations of seven cantilevers by using a single actuator and detector in air environment. The method is suitable for low-cost multiplexed portable biosensors.

MEMS based blood plasma viscosity sensor without electrical connections

A MEMS based viscometer is reported. The device has a disposable cartridge and a reader. The cartridge contains microfluidic channels and a MEMS cantilever sensor. The reader contains the actuator and the readout optics and electronics. A unique feature of the system is that both the actuation and the sensing are remote; therefore, no electrical connections are required between the reader and the cartridge. The reported sensor is capable of measuring viscosity with better than 0.01 cP resolution in a range of 0.8-14.1 cP, with less than 50 μl sample requirement. This range and sensitivity are sufficient for blood plasma viscosity measurements, which are in between 1.1-1.3 cP for healthy individuals and can be elevated to 3cP in certain diseases[1].

LoC sensor array platform for real-time coagulation measurements

This paper reports a MEMS-based sensor array enabling multiple clot-time tests in one disposable microfluidic cartridge using plasma. The versatile LoC (Lab-on-Chip) platform technology is demonstrated here for real-time coagulation tests (activated Partial Thrompoblastin Time (aPTT) and Prothrombin Time (PT)). The system has a reader unit and a disposable cartridge. The reader has no electrical connections to the cartridge, which consists of multiple microfluidic channels and MEMS microcantilevers placed in each channel. Microcantilevers are made of electro-plated nickel and actuated remotely using an external electro-coil. The read-out is also conducted remotely by a laser and the phase of the MEMS oscillator is monitored real-time. The system is capable of monitoring coagulation time with a precision estimated at 0.1sec.

MEMS biosensor for parallel and highly sensitive and specific detection of hepatitis

A label-free biosensor array that offers highly sensitive, high-dynamic-range and highly specific detection of Hepatitis A antigen is reported. Sensor array consists of Ni cantilevers with surfaces functionalized with Hepatitis A antibody. Cantilevers are self-actuated at resonance using a single electromagnetic drive coil. Detection of resonance frequency is optical and facilitated by diffraction gratings embedded on cantilevers. All antibody-antigen interactions take place within undiluted bovine serum providing a high background noise due to unspecific molecules. A minimum detection limit of less than 0.1 ng/ml target molecule concentration is demonstrated. A high dynamic range is achieved, which is greater than 1000∶1 concentration range. The proposed sensor array is shown to be compatible with most of the requirements of a hand-held biosensor including label-free, robust and real-time measurement with well integrated components.

Haemodynamic Recovery Properties of the Torsioned Testicular Artery Lumen

Testicular artery torsion (twisting) is one such severe vascular condition that leads spermatic cord injury. In this study, we investigate the recovery response of a torsioned ram testicular artery in an isolated organ-culture flow loop with clinically relevant twisting modes (90°, 180°, 270° and 360° angles). Quantitative optical coherence tomography technique was employed to track changes in the lumen diameter, wall thickness and the three-dimensional shape of the vessel in the physiological pressure range (10–50 mmHg). As a control, pressure-flow characteristics of the untwisted arteries were studied when subjected to augmented blood flow conditions with physiological flow rates up to 36 ml/min. Both twist and C-shaped buckling modes were observed. Acute increase in pressure levels opened the narrowed lumen of the twisted arteries noninvasively at all twist angles (at ∼22 mmHg and ∼35 mmHg for 360°-twisted vessels during static and dynamic flow experiments, respectively). The association between the twist-opening flow rate and the vessel diameter was greatly influenced by the initial twist angle. The biomechanical characteristics of the normal (untwisted) and torsioned testicular arteries supported the utilization of blood flow augmentation as an effective therapeutic approach to modulate the vessel lumen and recover organ reperfusion.

Increased Energy Loss Due to Twist and Offset Buckling of the Total Cavopulmonary Connection

The hemodynamic energy loss through the surgically implanted conduits determines the postoperative cardiac output and exercise capacity following the palliative repair of single-ventricle congenital heart defects. In this study, the hemodynamics of severely deformed surgical pathways due to torsional deformation and anastomosis offset are investigated. We designed a mock-up total cavopulmonary connection (TCPC) circuit to replicate the mechanically failed inferior vena cava (IVC) anastomosis morphologies under physiological venous pressure (9, 12, 15 mmHg), in vitro, employing the commonly used conduit materials: Polytetrafluoroethylene (PTFE), Dacron, and porcine pericardium. The sensitivity of hemodynamic performance to torsional deformation for three different twist angles (0 deg, 30 deg, and 60 deg) and three different caval offsets (0 diameter (D), 0.5D, and 1D) are digitized in three dimensions and employed in computational fluid dynamic (CFD) simulations to determine the corresponding hydrodynamic efficiency levels. A total of 81 deformed conduit configurations are analyzed; the pressure drop values increased from 80 to 1070% with respect to the ideal uniform diameter IVC conduit flow. The investigated surgical materials resulted in significant variations in terms of flow separation and energy loss. For example, the porcine pericardium resulted in a pressure drop that was eight times greater than the Dacron conduit. Likewise, PTFE conduit resulted in a pressure drop that was three times greater than the Dacron conduit under the same venous pressure loading. If anastomosis twist and/or caval offset cannot be avoided intraoperatively due to the anatomy of the patient, alternative conduit materials with high structural stiffness and less influence on hemodynamics can be considered. [DOI: 10.1115/1.4035981]

Time-Series Interactions of Gene Expression, Vascular Growth and Hemodynamics during Early Embryonic Arterial Development

The role of hemodynamic forces within the embryo as biomechanical regulators for cardiovascular morphogenesis, growth, and remodeling is well supported through the experimental studies. Furthermore, clinical experience suggests that perturbed flow disrupts the normal vascular growth process as one etiology for congenital heart diseases (CHD) and for fetal adaptation to CHD. However, the relationships between hemodynamics, gene expression and embryonic vascular growth are poorly defined due to the lack of concurrent, sequential in vivo data. In this study, a long-term, time-lapse optical coherence tomography (OCT) imaging campaign was conducted to acquire simultaneous blood velocity, pulsatile micro-pressure and morphometric data for 3 consecutive early embryonic stages in the chick embryo. In conjunction with the in vivo growth and hemodynamics data, in vitro reverse transcription polymerase chain reaction (RT-PCR) analysis was performed to track changes in transcript expression relevant to histogenesis and remodeling of the embryonic arterial wall. Our non-invasive extended OCT imaging technique for the microstructural data showed continuous vessel growth. OCT data coupled with the PIV technique revealed significant but intermitted increases in wall shear stress (WSS) between first and second assigned stages and a noticeable decrease afterwards. Growth rate, however, did not vary significantly throughout the embryonic period. Among all the genes studied, only the MMP-2 and CASP-3 expression levels remained unchanged during the time course. Concurrent relationships were obtained among the transcriptional modulation of the genes, vascular growth and hemodynamics-related changes. Further studies are indicated to determine cause and effect relationships and reversibility between mechanical and molecular regulation of vasculogenesis.

Two cantilever based sytem for viscosity and density monitoring

Viscosity and density measurements in liquids in real-time is challenging. Previous MEMS based approaches use frequency sweeps for the purpose and those methods are slow and not real-time. We show that high precision viscosity and density measurements are possible using two cantilevers with different widths and by tracking their frequencies with a Phase-Locked-Loop in real-time.