Shape Memory Alloy Capsule Micropump for Drug Delivery Applications.

We introduce a shape memory alloy (SMA) actuated micropump optimized for drug delivery applications. The proposed novel design integrates a built-in replaceable drug reservoir within the pump package forming a self-contained preloaded capsule pump with an overall pump volume of 424.7 µL. The new design results in a compact, simple, and inexpensive micropump and reduces the probability of contamination with attained almost zero dead volume values. The pump consists of NiTi-alloy SMA wires coiled on a flexible polymeric enclosure and actuated by joule heating. Unlike diaphragm and peristaltic SMA micropump designs that actuate transversely, our design is actuated longitudinally along the direction of the highest mechanical compliance resulting in large strokes in the order of 5.6 mm at 27% deflection ratio, actuation speed up to 11 mm/s, and static head pressures up to 14 kPa (105 mmHg) at 7.1 W input power; thus, high throughputs exceeding 2524 µL/min under free convention conditions could be achieved. A model was developed to optimize the pump's geometrical parameters and the enclosure material. The model concluded that low stiffness enclosure material combined with thinner SMA wire diameter would result in the maximum deflection at the lowest power rating. To prove its viability for drug delivery applications, the pump was operated at a constant discharge volume at a relatively constant static head pressure. Furthermore, a design of bicuspid-inspired polymeric check-valves is presented and integrated onto the pump to regulate the flow. Since the built-in reservoir is replaceable, the pump capsule can be reused multiple times and for multiple drug types.

Integrative functional genetic-epigenetic approach for selecting genes as urine biomarkers for bladder cancer diagnosis.

Early screening for bladder cancer (BC) holds the key to combat and control the increasing global burden of BC mortality. We presented a simple approach to characterize, analyze, and validate a panel of biomarkers in BC and their relationship to bilharziasis. We investigated voided urine and blood samples from patients with bladder cancer (n = 94), benign bladder lesions (n = 60), and age-matched normal controls (n = 56). This study was divided into the following phases. (1) We analyzed the expression of urinary Hyaluronoglucosaminidase 1 (HYAL1) protein in BC and control samples by zymography. (2) We performed bioinformatics analysis to retrieve a set of epigenetic regulators of HYAL1. (3) This set of three selected genes [long non-coding RNA-urothelial cancer associated 1(lncRNA-UCA1), microRNA-210, and microRNA-96] was then analyzed in the same urine samples used in phase I by quantitative real-time PCR. (4) A high reproducibility of gene selection results was also determined from statistical validation. The urinary expression of HYAL1 protein and its epigenetic regulators were higher in BC patients (P < .001). The receiver-operating characteristic curve analyses demonstrated that each one had good sensitivity and specificity for distinguishing BC patients from non-BC ones (HYAL1, 89.4 and 91.2 %; miR-210, 76.6 and 93 %; miR-96, 76.6 and 89.4 %; and lncRNA-UCA1, 91.5 and 96.5 %). There was a significant positive correlation between HYAL1 and the selected epigenetic biomarkers. The performance of this urine biomarker panel reached 100 % sensitivity and 89.5 % specificity for bladder cancer diagnosis.

Rapid detection of urinary long non-coding RNA urothelial carcinoma associated one using a PCR-free nanoparticle-based assay.

We developed a specific hybridization assay for direct detection of long non-coding RNA urothelial carcinoma associated-1 (lncRNA-UCA1). Total RNA was extracted from urine pellet samples (bladder carcinoma patients and controls). Then, we compared the developed nanoassay with quantitative real time polymerase chain reaction (qRT-PCR) results in detection of urine UCA1 in bladder cancer and control samples. The sensitivity and the specificity of UCA1 nanoassay were 92.1% and 93.3%, respectively. The concordance of the two methods was 98%. Interestingly, all bilharzial benign cases showed negative lncRNA-UCA1 using both methods. UCA1-nanoassay is a valid test for direct detection of urine UCA1 for bladder cancer detection.

Evaluation of urinary microRNA panel in bladder cancer diagnosis: relation to bilharziasis.

We assessed the differential expression of a urinary panel of microRNAs (miRs) in terms of potential application as diagnostic markers of bladder cancer (BC) and relationship to bilharziasis. We investigated voided urine samples and blood from patients with BC (n = 188), benign bladder lesions (n = 88), and age-matched controls (n = 92). Five miRs (miR-210, miR-10b, miR-29c, miR-221, and miR-23a) were selected from previous microarray signature profiling (released by miR2Disease). Afterward, they were validated using polymerase chain reaction array. The expression levels of miR-210, miR-10b, and miR-29c in the urine samples were significantly higher in BC (P < 0.001). The receiver-operating characteristic curve analyses demonstrated that each miR had good sensitivity and specificity for distinguishing patients with BC from patients without BC (miR-210, 71.3% and 91.1%; miR-10b, 80.9% and 91.1%; and miR-183, 71.3% and 88.9%). On combining the 3 miR detection data with the urinary cytology, the results sensitivity increased to 95.2%. Relative quantity mean rank of the miR-29c was significantly higher in the bilharzial-positive patients compared with bilharzial-negative patients. To conclude, urine miR-210, miR-10b, and miR-29c are promising tumor markers for BC: bilharzial and nonbilharzial.

Evaluation of urinary HURP mRNA as a marker for detection of bladder cancer: relation to bilharziasis.

This study was carried out to assess the efficacy of urinary hepatoma up-regulated protein (HURP) RNA in bladder cancer diagnosis and its relation to bilharziasis. Voided urine samples and blood were collected from 344 consecutive participants: 211 patients diagnosed with bladder cancer, 71 patients with benign urological disorders and 62 healthy volunteers. Serologic assessment of schistosomiasis antibody in sera, urine cytology and estimation of HURP RNA by reverse transcription polymerase chain reaction in urothelial cells was carried out in all samples. HURP RNA expression showed a significant difference among the three investigated groups. The best cutoff point for HURP RNA was determined as 0.0132 at 78.67 % sensitivity and 94 % specificity. The sensitivity of urine cytology was improved when combined with HURP RNA in detection of early stage (77.3 %), low grade (85.3 %) and bilharzial bladder cancer (78.1 %). Detection of urinary HURP RNA is a useful non-invasive test for early detection of bladder cancer and bilharzial bladder cancer and it improves sensitivity of urine cytology up to 91 %.