Comprehensive quantitative analysis of erythrocytes and leukocytes using trace volume of human blood using microfluidic-image cytometry and machine learning.

A diagnostic test based on microfluidic image cytometry and machine learning has been designed and applied for accurate classification of erythrocytes and leukocytes, including a unique fully-automated 5-part quantitative differentiation into neutrophils, lymphocytes, monocytes, eosinophils, and basophils, using minute amounts of whole blood in a single counting chamber. A low-cost disposable multilayer microdevice for microfluidic image cytometry was developed that comprises a 1 mm × 22 mm × 70 µm (w × l × h) rectangular microchannel, allowing the analysis of trace volume of blood (20 µL) for each assay. Automated analysis of digitized binary images applying a border following algorithm was performed allowing the qualitative analysis of erythrocytes. Bright-field imaging was used for the detection of erythrocytes and fluorescence imaging for 5-part differentiation of leukocytes after acridine orange staining, applying a convolutional neural network enabling unparalleled speed for identification and automated morphology classification yielding 98.57% accuracy. Blood samples were obtained from 30 volunteers and count values did not significantly differ from data obtained using a commercial automated hematology analyzer.

High-Efficiency Inertial Separation of Microparticles Using Elevated Columned Reservoirs and Vortex Technique for Lab-on-a-Chip Applications.

The discovery of circulating tumor cells (CTCs) has envisioned an excellent outlook for cancer diagnosis and prognosis. Among numerous efforts proposed for CTCs isolation, vortex separation is a well-known method for capturing CTCs from blood due to its applicability, low sample volume requirement, and ability to retain cell viability. It is a label-free, passive, low-cost, and automated method, making it an ideal solution for lab-on-a-chip applications. The previous designs that employed vortex technology have shown reaching high throughput and 70% separation efficiency although it was after three processing cycles which are not desired. Inspired by our earlier design, in this work, we redesigned the chip geometry by elevating the columned reservoir height to capture more particles and consequently reduce particle-particle collision, eventually improving efficiency. So, a height-variable chip with fewer elevated columned reservoirs (ECRs) was employed to isolate 20 µm microparticles representing CTCs from 8 µm microparticles. Also, numerical simulations were conducted to investigate the third axis contribution to the separation mechanism. The new design with ECRs resulted in a 14% increase in average efficiency, reaching ∼80% ± 8.3% in microparticle separation and 61% purity. Moreover, the proposed chip geometry demonstrated more than three times higher capacity in retaining orbiting particles up to 1300 in peak performance without sacrificing efficiency compared to earlier single-layer designs. We came up with an upgraded injection system to facilitate this chip characterization. We also presented an effortless and straightforward approach for purging air bubbles trapped inside the reservoirs to preserve regular chip operation, especially where there is a mismatch between channel and reservoir heights.

Clinical Validation of a Smartphone-based Handheld ECG Device: A Validation Study.

BACKGROUND: Remote cardiac monitoring and screening have already become an integral telemedicine component. The wide usage of several different wireless electrocardiography (ECG) devices warrants a validation study on their accuracy and reliability. METHODS: Totally, 300 inpatients with the Nabz Hooshmand-1 handheld ECG device and the GE MAC 1200 ECG system (as the reference) were studied to check the accuracy of the devices in 1 and 6-limb lead performance. Simultaneous 10-second resting ECGs were assessed for the most common ECG parameters in lead I. Afterward, 6-lead ECGs (limb leads), were performed immediately and studied for their morphologies. RESULTS: Of the 300 patients, 297 had acceptable ECG quality in both devices for simultaneous lead I ECGs. The ECGs were inspected on-screen by a cardiologist for their rhythms, rates, axes, numbers, morphologies of premature atrial and ventricular beats, morphologies and amplitudes of PQRST waves, P-wave durations, QRS-wave durations, P-R intervals, and QT intervals. No significant differences were detected between the devices, and no major abnormalities were missed. Six-limb lead ECGs were obtained in 284 patients, of whom 281 had acceptable quality in ECGs by both devices. The morphology matching evaluation of the ECGs demonstrated an overall 98% compatibility rate, with the highest compatibility in lead I and the lowest in lead augmented vector foot. CONCLUSIONS: The diagnosis of critical pathological rhythms, including atrial fibrillation and high-grade atrioventricular node block, was not missed by the Nabz Hooshmand-1 and GE MAC 1200 ECG devices. Accordingly, rhythm detection as the primary purpose of handheld ECG devices was highly accurate. Both devices had acceptable sensitivity to diagnose long P-R and long and short QT intervals. Although the modern technology of smartphones and the physical inability for the 6-limb mode might cause old patients difficulty in utilizing such devices, their use for screening and follow-up is safe.

Buried-Gate MWCNT FET-Based Nanobiosensing Device for Real-Time Detection of CRP.

C-reactive protein (CRP), an acute-phase protein synthesized in the liver in response to inflammation, is one of the biomarkers used for the detection of several diseases. Sepsis and cardiovascular diseases are two of the most important diseases for which detection of CRP at very early stages in the clinical range can help avert serious consequences. Here, a CNT-based nanobiosensing system, which is portable and reproducible, is used for label-free, online detection of CRP. The system consists of an aptameric CNT-based field-effect transistor benefiting from a buried gate geometry with Al2O3 as a high dielectric layer and can reflect the pro-cytokine concentration. Test results show that the device responds to CRP changes within 8 min, with a limit of detection as low as 150 pM (0.017 mg L-1). The device was found to have a linear behavior in the range of 0.43-42.86 nM (0.05-5 mg L-1). The selectivity of the device was tested with TNF-α, IL-6, and BSA, to which the nanosensing system showed no significant response compared with CRP. The device showed good stability for 14 days and was completely reproducible during this period. These findings indicate that the proposed portable system is a potential candidate for CRP measurements in the clinical range.

Point of care testing: The impact of nanotechnology.

Point-of-care (POC) diagnostic devices are integral in the health care system and particularly for the diagnosis and monitoring of diseases. POC testing has a variety of advantages including the ability to provide rapid and accurate results, ease of use, low cost, and little need for specialized equipment. One of the goals of POC testing is the development of a chip-based, miniaturized, portable, and self-containing system that allows for the assay of different analytes in complex samples. To achieve these goals, many researchers have focused on paper-based and printed electrode technologies as the material for fabricating POC diagnostic systems. These technologies are affordable, sensitive, user-friendly, rapid, and scalable for manufacturing. Moreover, the combination such devices with nanomaterials provide a path for the development of highly sensitive and selective biosensors for future generation POC tools. This review article discusses present technologies in on-site or at home POC diagnostic assays implemented in paper-based microfluidic and screen printing devices over the past decade as well as in the near future. In addition, recent advances in the application of nanomaterials such as gold nanoparticles, carbon nanotubes (CNTs), magnetic nanoparticles, and graphene in POC devices will be reviewed. The factors that limit POC testing to become real world products and future directions are also identified.

Observation and measurement of negative differential resistance on PtSi Schottky junctions on porous silicon.

Nanosize porous Si is made by two step controlled etching of Si. The first etching step is carried on the Si surface and the second is performed after deposition of 75 Å of platinum on the formed surface. A platinum silicide structure with a size of less than 25 nm is formed on the porous Si surface, as measured with an Atomic Forced Microscope (AFM). Differential resistance curve as a function of voltage in 77 K and 100 K shows a negative differential resistance and indicates the effect of quantum tunneling. In general form, the ratio of maximum to minimum tunneling current (PVR) and the number of peaks in I-V curves reduces by increasing the temperature. However, due to accumulation of carriers behind the potential barrier and superposition of several peaks, it is observed that the PVR increases at 100 K and the maximum PVR at 100 K is 189.6.

Low Magnetic Field Detection Using a CuPt Nano Structure Made on a SiO(2)/Si Structure.

A Si/SiO(2)/CuPt structure is formed by depositing a very thin SiO(2) layer between CuPt and P-type Si layers using e-beam evaporation. SEM images show the formation of CuPt nano clusters with an average size of less than 100 nm. This structure shows high sensitivity to applied magnetic fields at 77K and at low and high dc voltages such that magnetic field as low as 6 mT is detected using I-V and I-B measurements. The variation of current with various magnetic field strength at the constant voltage shows also an oscillatory behavior. The sensitivity of this structure to magnetic fields is believed to be due to small nano size of the platinum-copper structures as well as their discrete energy states and the tunneling of carriers into the insulating layer. Our results indicate that this structure may be a good candidate for small, simple, low cost and sensitive low magnetic field detectors.