Fully integrated point-of-care blood cell count using multi-frame morphology analysis.

Point-of-care testing (POCT) of blood cell count (BCC) is an emerging approach that allows laypersons to identify and count whole blood cells through simple manipulation. To date, POCTs for BCC were mainly achieved by "stationary" images through blood smears or single-laity arranged cells in the microwell, making it difficult to obtain statistically sufficient numbers of cells. In this work, we present a fully integrated POCT device solely using "in-flow" imaging of 3 µL fingertip whole blood for improved identification and counting accuracy of BCC analysis. A miniaturized magnetic stirring module was integrated to maintain the temporal stability of cell concentration. A relatively high throughput (∼8000 cells/min) with a 30-fold dilution ratio of whole blood can be tested for as long as 1 h to examine sufficient numbers of cells, and the subclass cell concentration keeps constant. To improve the identification accuracy, multi-frame "in-flow" imaging was used to track the cell motion trails with multi-angle morphology analysis. This proof-of-concept was then validated with healthy whole blood samples and 75 cases of clinical patients with abnormal concentrations of red blood cells (RBCs), white blood cells (WBCs), and platelets (PLT). The average precision (AP) value of WBCs identification was improved from 0.8622 to 0.9934 using the multi-frame analysis method. And the high fitting degrees (>0.98) between our POCT device and the commercial clinical equipment indicated good agreement. This POCT device is user-friendly and cost-effective, making it a potential tool for diagnosing abnormal blood cell morphology or concentration in the field setting.

Modeling pyramidal silicon nanopores with effective ion transport.

While the electrical models of the membrane-based solid-state nanopores have been well established, silicon-based pyramidal nanopores cannot apply these models due to two distinctive features. One is its 35.3° half cone angle, which brings additional resistance to the moving ions inside the nanopore. The other is its rectangular entrance, which makes calculating the access conductance challenging. Here, we proposed and validated an effective transport model (ETM) for silicon-based pyramidal nanopores by introducing effective conductivity. The impact of half cone angle can be described equivalently using a reduced diffusion coefficient (effective diffusion coefficient). Because the decrease of diffusion coefficient results in a smaller conductivity, effective conductivity is used for the calculation of bulk conductance in ETM. In the classical model, intrinsic conductivity is used. We used the top-down fabrication method for generating the pyramidal silicon nanopores to test the proposed model. Compared with the large error (≥25% in most cases) when using the classical model, the error of ETM in predicting conductance is less than 15%. We also found that the ETM is applicable when the ratio of excess ion concentration and bulk ion concentration is smaller than 0.2. At last, it is proved that ETM can estimate the tip size of pyramidal silicon nanopore. We believe the ETM would provide an improved method for evaluating the pyramidal silicon nanopores.

Ionic Current Rectification: A Result of the Series Connection of Nanochannels with Different Dukhin Numbers.

Originating from the ionic concentration polarization, ionic current rectification (ICR) is closely related to ion selectivity. Since it is the region with the greatest selectivity, the tip of the conical nanopore became the focus of research. However, even if the characteristic of the tip is fixed, the changes of pore length and cone angle still affect the magnitude of ICR─rectification factor (RF). This shows that only focusing on the selectivity of the tip is not comprehensive. Through the simulations based on the one-dimensional Poisson-Nernst-Planck model, it is found that the pore length and cone angle can influence the RF by changing the Dukhin number of pore base (Dubase). Here, Du is a parameter describing the ratio of excess ion concentration and bulk ion concentration. In addition, it is proved that the RF is determined by Dutip (Du of the pore tip) and Dubase together. On the basis of the results, we suggest that a uniformly charged conical nanopore can be equivalent to the series connection of many ultrashort nanochannels with different Du. The differences in Du between adjacent channels lead to unbalanced ion transport, ultimately leading to enrichment or depletion of ion concentration under different polarities. Besides, ICR in bipolar diodes also exhibits Du dependence. We anticipate that this work will provide help to understand the mechanism behind ICR.

The effect of laser irradiation on reducing the noise of solid-state nanopore.

The performance of solid-state nanopore is affected by the noise level. This study aimed to investigate the effect of laser irradiation on the noise performance of solid-state nanoporein situ. Laser irradiation is applied to fresh and contaminated nanopores. The measurement results show that the noise of fresh and contaminated nanopores decreases with the laser power and there is a threshold of laser power in reducing the noise of contaminated nanopores. The possible reasons for reducing noise in the laser irradiation process are discussed. The laser treatment is proven to provide a convenient method for reducing the noise of solid-state nanopore.

Confocal scanning photoluminescence for mapping electron and photon beam-induced microscopic changes in SiN x during nanopore fabrication.

Focused electron and laser beams have shown the ability to form nanoscale pores in SiN x membranes. During the fabrication process, areas beyond the final nanopore location will inevitably be exposed to the electron beams or the laser beams due to the need for localization, alignment and focus. It remains unclear how these unintended exposures affect the integrity of the membrane. In this work, we demonstrate the use of confocal scanning photoluminescence (PL) for mapping the microscopic changes in SiN x nanopores when exposed to electron and laser beams. We developed and validated a model for the quantitative interpretation of the scanned PL result. The model shows that the scanning PL result is insensitive to the nanopore size. Instead, it is dominated by the product of two microscopic material factors: quantum yield profile (i.e. variations in electronic structure) and thickness profile (i.e. thinning of the membrane). We experimentally demonstrated that the electron and laser beams could alter the material electronic structures (i.e. quantum yield) even when no thinning of the membrane occurs. Our results suggest that minimizing the unintended e-beam or laser beam to the SiN x during the fabrication is crucial if one desires the microscopic integrity of the membrane.

A novel flexible room temperature ethanol gas sensor based on SnO2 doped poly-diallyldimethylammonium chloride.

A novel flexible room temperature ethanol gas sensor was fabricated and demonstrated in this paper. The polyimide (PI) substrate-based sensor was formed by depositing a mixture of SnO2 nanopowder and poly-diallyldimethylammonium chloride (PDDAC) on as-patterned interdigitated electrodes. PDDAC acted both as the binder, promoting the adhesion between SnO2 and the flexible PI substrate, and the dopant. We found that the response of SnO2-PDDAC sensor is significantly higher than that of SnO2 alone, indicating that the doping with PDDAC effectively improved the sensor performance. The SnO2-PDDAC sensor has a detection limit of 10 ppm at room temperature and shows good selectivity to ethanol, making it very suitable for monitoring drunken driving. The microstructures of the samples were examined by scanning electron microscopy (SEM), X-ray diffraction (XRD), transmission electron microscope (TEM) and Fourier transform infrared spectra (FT-IR), and the sensing mechanism is also discussed in detail.