Correlation between X-ray tube current exposure time and X-ray photon number in GATE.

BACKGROUND: X-ray image quality relies heavily on the emitted X-ray photon number which depends on X-ray tube current and exposure time. To accurately estimate the absorbed dose in an imaging protocol, it is better to simulate the X-ray imaging with a Monte Carlo platform such as GATE (Geant4 Application for Tomographic Emission). Although input of GATE is the X-ray photon number of the simulated X-ray tube, it lacks a good way to setup the photon number for a desired X-ray tube current setting. OBJECTIVE: To provide a method to correlate the experimental X-ray tube current exposure time and the X-ray photon number in GATE. METHODS: The accumulated radiation dose of a micro-computed tomography (CT) X-ray tube was recorded at different current exposure times with a general-purpose ion chamber. GATE was used to model the experimental microCT imaging system and calculate the total absorbed dose (cGy) in the sensitive volume of the ion chamber with different X-ray photon numbers. Linear regression models are used to establish a correlation between the estimated X-ray photon number and the X-ray tube settings. At first, one model establishes the relationship between the experimentally measured dose and the X-ray tube setting. Then, another model establishes a relationship between the simulated dose and the X-ray number in GATE. At last, by correlating these two models, a regression model to estimate the X-ray output number from an experimental X-ray tube setting (mAs) is obtained. RESULTS: For a typical micro-CT scan, the X-ray tube is operated at 50 kVp and 0.5 mA for a 500 ms exposure time per projection (0.25 mAs). For these X-ray imaging parameters, the X-ray number per projection is estimated to be 3.613×106 with 1.0 mm Al filter. CONCLUSION: The findings of this work provide an approach to correlate the experimental X-ray tube current exposure time to the X-ray photon number in the GATE simulation of the X-ray tube to more accurately determine radiation dose for an imaging protocol.

Contrast agents for x-ray luminescence computed tomography.

Imaging probes are an important consideration for any type of contrast agent-based imaging method. X-ray luminescence imaging (XLI) and x-ray luminescence computed tomography (XLCT) are both contrast agent-based imaging methods that employ x-ray excitable scintillating imaging probes that emit light to be measured for optical imaging. In this work, we compared the performance of several select imaging probes, both commercial and self-synthesized, for application in XLI/XLCT imaging. Commercially available cadmium telluride quantum dots (CdTe QDs) and europium-doped gadolinium oxysulfide (GOS:Eu) microphosphor as well as synthesized NaGdF4 nanophosphors doped with either europium or terbium were compared through their x-ray luminescence emission spectra, luminescence intensity, and also by performing XLCT scans using phantoms embedded with each of the imaging probes. Each imaging probe displayed a unique emission spectrum that was ideal for deep-tissue optical imaging. In terms of luminescence intensity, due to the large particle size, GOS:Eu had the brightest emission, followed by NaGdF4:Tb, NaGdF4:Eu, and finally the CdTe QDs. Lastly, XLCT scans showed that each imaging probe could be reconstructed with good shape and location accuracy.

QuickAnalysis: A Software Designed and Developed for a Portable On-Site Pathogen Detection System.

To develop a software program used for controlling the portable on-site pathogen detection system which is based on real-time PCR, this software is developed by C# over the Microsoft Visual Studio 2013 and used on local computers which are equipped with Windows systems. Taking the actual demand as the guidance, it constructs according to the framework design and unifies the barcode technology, the cloud service, and the Bluetooth technology. Based on the above methods, this software can meet the demands of the system such as free experiment design, auto-control of the hardware and efficient data management. During the operation of this program, the serial port and network communication between it and the device and web server remains stable, no matter it is processing the data collection or data analysis and display. It is feasible and practical to apply this software to the portable on-site pathogen detection system in clinical practices and research work.

The Liquid Level Detection System Based on Pressure Sensor.

Micro-liquid distribution operation has been a core part of the fully automatic liquid handling platform in clinical testing. Accurate and fast automatic detection of liquid level with disposable tip is the precondition to ensure the stability of the whole operation of liquid handling platform. By further research on the liquid level sensing technology of pressure sensor, in this paper we designed a new type of accurate and stable micro-liquid level detection system and verified its stability, instantaneity and accuracy by setting up a small reagent distribution platform. It was shown that the liquid level detection system designed in this paper has reliable stability, good instantaneity and high accuracy, with the liquid level detecting accuracy up to 100%, the response speed after detecting the liquid level reaching millisecond and the depth in the liquid level less than 0.3 mm. Besides, there is no limit on the physical and chemical properties of the liquids to be tested, which is consistent with the technical indicators of the liquid handling platform.

Emerging mRNA Technology for Liver Disease Therapy.

Liver diseases have consistently posed substantial challenges to global health. It is crucial to find innovative methods to effectively prevent and treat these diseases. In recent times, there has been an increasing interest in the use of mRNA formulations that accumulate in liver tissue for the treatment of hepatic diseases. In this review, we start by providing a detailed introduction to the mRNA technology. Afterward, we highlight types of liver diseases, discussing their causes, risks, and common therapeutic strategies. Additionally, we summarize the latest advancements in mRNA technology for the treatment of liver diseases. This includes systems based on hepatocyte growth factor, hepatitis B virus antibody, left-right determination factor 1, human hepatocyte nuclear factor α, interleukin-12, methylmalonyl-coenzyme A mutase, etc. Lastly, we provide an outlook on the potential of mRNA technology for the treatment of liver diseases, while also highlighting the various technical challenges that need to be addressed. Despite these difficulties, mRNA-based therapeutic strategies may change traditional treatment methods, bringing hope to patients with liver diseases.

Emerging platelet-based drug delivery systems.

Drug delivery systems are becoming increasingly utilized; however, a major challenge in this field is the insufficient target of tissues or cells. Although efforts with engineered nanoparticles have shown some success, issues with targeting, toxicity and immunogenicity persist. Conversely, living cells can be used as drug-delivery vehicles because they typically have innate targeting mechanisms and minimal adverse effects. As active participants in hemostasis, inflammation, and tumors, platelets have shown great potential in drug delivery. This review highlights platelet-based drug delivery systems, including platelet membrane engineering, platelet membrane coating, platelet cytoplasmic drug loading, genetic engineering, and synthetic/artificial platelets for different applications.

From biogenesis to aptasensors: advancements in analysis for tumor-derived extracellular vesicles research.

Extracellular vesicles (EVs) are enclosed by a nanoscale phospholipid bilayer membrane and typically range in size from 30 to 200 nm. They contain a high concentration of specific proteins, nucleic acids, and lipids, reflecting but not identical to the composition of the parent cell. The inherent characteristics and variety of EVs give them extensive and unique advantages in the field of cancer identification and treatment. Recently, EVs have been recognized as potential tumor markers for the detection of cancer. Aptamers, which are molecules of single-stranded DNA or RNA, demonstrate remarkable specificity and affinity for their targets by adopting distinct tertiary structures. Aptamers offer various advantages over their protein counterparts, such as reduced immunogenicity, the ability for convenient large-scale synthesis, and straightforward chemical modification. In this review, we summarized EVs biogenesis, sample collection, isolation, storage and characterization, and finally provided a comprehensive survey of analysis techniques for EVs detection that are based on aptamers.

Cell-SELEX and application research of a DNA aptamer against esophageal squamous cell carcinoma (ESCC) cell line TE-1.

Esophageal cancer is a common cancer with high morbidity and mortality that severely threatens the safety and quality of human life. The strong metastatic nature of esophageal cancer enables it to metastasize more quickly and covertly, making it difficult for current diagnostic and treatment methods to achieve efficient early screening, as well as timely and effective treatment. As a promising solution, nucleic acid aptamers, a kind of special single-stranded DNA or RNA oligonucleotide selected by the Systematic Evolution of Ligands by Exponential Enrichment (SELEX) technology, can specifically bind with different molecular targets. In this paper, random DNA single-stranded oligonucleotides were used as the initial library. Using TE-1 cells and HEEC cells as targets, specific binding sequences were selected by 15 rounds of the cell-SELEX method, and the aptamer sequence that binds to TE-1 cells with the most specificity was obtained and named Te4. The Te4 aptamer was further validated for binding specificity, binding affinity, type of target, in vitro cytotoxicity when conjugated with DOX(Te4-DOX), and in vivo distribution. Results of in vitro validation showed that Te4 has outstanding binding specificity with a Kd value of 51.16 ± 5.52 nM, and the target type of Te4 was preliminarily identified as a membrane protein. Furthermore, the cytotoxicity experiment showed that Te4-DOX has specific cytotoxicity towards cultured TE-1 cells. Finally, the results of the in vivo distribution experiment showed that the Te4 aptamer is able to specifically target tumor regions in nude mice, showing great potential to be applied in future diagnosis and targeted therapy of esophageal cancer.

Superfast Scan of Focused X-Ray Luminescence Computed Tomography Imaging.

X-ray luminescence computed tomography (XLCT) is a hybrid molecular imaging modality having the high spatial resolution of x-ray imaging and high measurement sensitivity of optical imaging. Narrow x-ray beam based XLCT imaging has shown promise for high spatial resolution imaging of luminescent targets in deep tissues, but the slow acquisition speed limits its applications. In this work, we have introduced a superfast XLCT scan scheme based on the photon counter detector and a fly-scanning method. The new scan scheme is compared with three other scan methods. We have also designed and built a single-pixel x-ray detector to detect object boundaries automatically. With the detector, we can perform the parallel beam CT imaging with the XLCT imaging simultaneously. We have built the prototype XLCT imaging system to verify the proposed scan scheme. A phantom embedded with a set of four side-by-side cylindrical targets was scanned. With the proposed superfast scan scheme, we have achieved 43 seconds per transverse scan, which is 28.6 times faster than before with slightly better XLCT image quality. The superfast scan allows us to perform 3D pencil beam XLCT imaging in the future.

Oxygenation imaging in deep tissue with X-Ray luminescence computed tomography (XLCT).

Oxygenation concentration of tissue is an important factor in culturing stem cells and in studying the therapy response of cancer cells. The hypoxia bone marrow is the site to harbor cancer cells. Thus, direct high-resolution measurements of molecular 𝑂2 would provide powerful means of monitoring cultured stem cells and therapied cancer cells. We proposed an imaging approach to measure oxygenation concentration in deep tissues, based on the XLCT, with combined strengths of high chemical sensitivity and high spatial resolution. We have developed different biosensing films for oxygenation measurements and tested these films with X-ray luminescent experiments. We have also performed phantom experiments with multiple targets to validate the XLCT imaging system with measurements at two channels.

A miniaturized and integrated dual-channel fluorescence module for multiplex real-time PCR in the portable nucleic acid detection system.

A portable nucleic acid detection (PNAD) system based on real-time polymerase chain reaction (real-time PCR) has been developed for point-of-care testing (POCT) of infectious disease pathogens. In order to achieve "sample-in, result-out" while keeping the system compact, the hardware system integrates optical, thermal and motion control modules in a limited space for nucleic acid extraction, purification, amplification and detection. Among these hardware modules, the fluorescence module is one of the most important modules, because its performance directly affects the accuracy and sensitivity of the testing results. In this paper, a miniaturized, high-sensitivity and integrated dual-channel fluorescence module have been proposed for the homemade PNAD system. Based on the principle of confocal optical path, two group of excitation-emission optical paths of different wavelengths are integrated in a small space. In terms of circuitry, a current-light dual negative feedback light emitting diode (LED) drive circuit is applied to improve the stability of the excited light source. All optical and electronic components are integrated in a metal box of 55 mm × 45 mm × 15 mm, that helps miniaturize the detection system. Two different modules have been assembled to fit various fluorescent dyes or probes with the set of excitation and emission as follow: module 1#: 470 nm/525 nm, 570 nm/630 nm; module 2#: 520 nm/570 nm, 630 nm/690 nm. Finally, hepatitis B virus (HBV) concentration gradient detection and multiplex detection of different gene targets of SARS-CoV-2 are carried out on the PNAD system equipped with these two fluorescence modules for evaluating their performances. Compared with the commercial real-time PCR instrument, our fluorescence module has good stability and detection sensitivity.

A Highly Integrated and Diminutive Fluorescence Detector for Point-of-Care Testing: Dual Negative Feedback Light-Emitting Diode (LED) Drive and Photoelectric Processing Circuits Design and Implementation.

As an important detection tool in biochemistry, fluorescence detection has wide applications. Quantitative detection can be achieved by detecting fluorescence signals excited by excitation light at a specific wavelength range. Therefore, the key to fluorescence detection is the stable control of the excitation light and the accurate acquisition of weak photoelectric signals. Moreover, to improve portability and instantaneity, devices are developing in miniaturization and integration. As the core of such devices, fluorescence detectors should also have these features. Under this circumstance, we designed a highly integrated and diminutive fluorescence detector and focused on its excitation light driving and photoelectric signal processing. A current-light dual negative feedback light-emitting diode (LED) driving circuit was proposed to obtain constant current and luminance. In addition, a silicon photodiode (PD) was used to receive and convert the fluorescence signal to an electric signal. Then, amplifying, filtering, and analog-to-digital (A/D) converting were applied to make the detection of weak fluorescence signals possible. The test results showed that the designed circuit has wonderful performance, and the detector shows good linearity (R2 = 0.9967) and sensitivity (LOD = 0.077 nM) in the detection of fluorescein sodium solution. Finally, a real-time fluorescence polymerase chain reaction (real-time PCR) of Legionella pneumophila was carried out on a homemade platform equipped with this detector, indicating that the detector met the requirements of real-time PCR detection.

Super-Fast Three-Dimensional Focused X-ray Luminescence Computed Tomography with a Gated Photon Counter.

X-ray luminescence computed tomography (XLCT) is a hybrid molecular imaging modality combining the merits of both x-ray imaging (high spatial resolution) and optical imaging (high sensitivity to tracer nanophosphors). Narrow x-ray beam based XLCT imaging has shown promise for high spatial resolution imaging, but the slow acquisition speed limits its applications for in vivo imaging. We introduced a continuous scanning scheme to replace the selective excitation scheme to improve imaging speed in a previous study. Under the continuous scanning scheme, the main factor that limits the scanning speed is the data acquisition time at each interval position. In this work, we have used a gated photon counter (SR400, Stanford Research Systems) to replace the high-speed oscilloscope (MDO3104, Tektronix) to acquire measurement data. The gated photon counter only counts the photon peaks in each measurement interval, while the oscilloscope records the entire waveform including both background noise data and photon peak data. The photon counter records much less data without losing any relevant information, which makes it ideal for super-fast three-dimensional (3D) imaging. We have built prototype XLCT imaging systems of both types and performed both single target and multiple target phantom experiments in 3D. The results have verified the feasibility of our proposed photon counter based system and good 3D imaging capabilities of XLCT within a reasonable time, yielding a 14 times faster scanning time compared with the oscilloscope based XLCT system. Now, the total scan time is reduced to 27 seconds per transverse section.

A New Hematocrit Measurement Method Using a Chemiluminescence Biosensor and Its Application in a Chemiluminescence Immunoassay Platform for Myocardial Markers Detection with Whole Blood Samples.

The accuracy and precision of analyte concentrations measured in whole blood by chemiluminescence immunoassay (CLIA) have been significantly affected by erythrocytes, which leads to poor application of whole blood CLIA in clinical practice. In this work, a chemiluminescence biosensing optical platform for blood hematocrit (HCT) analysis using MAGICL 6000 (Getein Biotechnology, Nanjing, China) was designed, implemented, and fully characterized. The developed method was successfully applied to determine various HCT levels of human blood from 0% to 65%, with a correlation coefficient of 0.9885 compared with the conventional method (Sysmex XE 5000, Kobe, Japan). A mathematical model was developed to quantitatively evaluate the impact of HCT on the results of two sample types (whole blood vs. plasma). Combining the established HCT method and mathematical model with CLIA on MAGICL 6000, the precision was significantly improved by almost 20%. Comparison studies using whole blood samples and corresponding plasma samples showed that the square of the correlation coefficients of troponin I (cTnI), myoglobin (MYO), creatine kinase MB (CK-MB), and N-terminal pro-hormone brain natriuretic peptide (NT-proBNP) were increased to 0.9992, 0.9997, 0.9996, and 0.9994, respectively, showing a great potential for clinical application.

A Detection-Service-Mobile Three-Terminal Software Platform for Point-of-Care Infectious Disease Detection System.

The traditional infectious disease detection process is cumbersome, and there is only a single application scenario. In recent years, with the development of the medical industry and the impact of the epidemic situation, the number of infectious disease detection instruments based on nursing point detection has been increasing. Due to this trend, many detection instruments and massive detection data urgently need to be managed. In addition, the experiment failed due to the abnormal fluorescence curve generated by a human operator or sample impurities. Finally, the geographic information system has also played an active role in spreading and preventing infectious diseases; this paper designs a "detection-service-mobile" three-terminal system to realize the control of diagnostic instruments and the comprehensive management of data. Machine learning is used to classify the enlarged curve and calculate the cycle threshold of the positive curve; combined with a geographic information system, the detection results are marked on the mobile terminal map to realize the visual display of the positive results of nucleic acid amplification detection and the early warning of infectious diseases. In the research, applying this system to portable field pathogen detection is feasible and practical.

Fast and Accurate Control Strategy for Portable Nucleic Acid Detection (PNAD) System Based on Magnetic Nanoparticles.

Portable nucleic acid detection (PNAD) systems are performed for sample processing, amplification and detection automatically in an individual device realizing "sample in, answer out." For this goal, numerous function modules should be integrated in a diminutive device, in which temperature controller is one of the most important modules. In a nucleic acid detection process, both sample processing and polymerase chain reaction (PCR) require fast and accurate temperature control to increase concentration and purity of the extraction product and to improve amplification efficiency. In this paper, a dual-channel temperature controller for PNAD systems is developed, which contains a printed circuit board (PCB) and an integrated control program with a fast and accurate control strategy. According to the principle of nucleic acid detection based on magnetic nanoparticles, the controller can work in different modes such as high-precision heating control for nucleic acid extraction, rapid thermal cycle control for PCR, and rate adjustable constant heating/cooling control for melting curve. Evaluatively, the average heating/cooling rate of the module can exceed about 6 C/s, while the temperature fluctuation was less than ± 0.1°C, which can meet the demands of PNAD systems very well.

Improvement and Application of qPCR (Real-Time Quantitative Polymerase Chain Reaction) Data Processing Method for Home-Made Integrated Nucleic Acid Detection System.

Because it has many advantages such as rapidity and accuracy, nucleic acid detection is applied to infectious disease diagnosis more and more. An automatic integrated nucleic acid detection system based on real-time PCR is developed by our research group to conduct point-of-care testing of infectious pathogens. The home-made detection system collects fluorescence data in each PCR cycle through an integrated dual-channel fluorescence detection module and then real-time fluorescence curves are drawn by the software, which can tell the results of the diagnostics after some processing and analysis. However, owing to the disturbance of the environment or the imperfect of nucleic acid extraction before PCR, the fluorescence curves sometimes may contain several abnormal points. For the purpose of enhancing its ability to deal with these iffy curves and improve the accuracy of the testing results, in this study, the SDM-based qPCR data processing algorithm was studied and 11 groups of qPCR data that have different flaws from the clinical samples detected by this system were chosen to prove the practicability of the method. In comparison with the conventional threshold-based method, the Cq values calculated by the SDM-based method were more close to the actual values, meaning it can overcome the shortcomings of the conventional methods such as being unable to accommodate noise and being unable to avoiding abnormal data. With the improvement of this data processing algorithm, the stability of our system and the reliability and accuracy of the results are greatly improved.

Performance Evaluation of a Novel Sample In-Answer Out (SIAO) System Based on Magnetic Nanoparticles.

In recent years, the prevention, control, diagnosis and treatment of infectious diseases has become a global focus for public health. Traditional methods for pathogen testing have some major disadvantages including the need for highly skilled staff and expensive instrumentation, while procedural aspects are complex and sensitive to the environment. These shortcomings have greatly limited the application of traditional testing in on site pathogen detection. In this paper, we present a new point-of-care-testing (POCT) system based on magnetic nanoparticles that enable sample in-answer out (SIAO) automated real-time testing for pathogens. Various performance tests were conducted on the instrument. Nucleic acid extraction efficiencies of SIAO versus manual systems were 95.49% and 84.33%, respectively. Real-time PCR by two methods (TaqMan-based probe and SYBR green dye) in the SIAO system was achievable, with comparable results to the manual method. Nucleic acid testing with the SIAO system was repeatable and better than with manual testing. The SIAO system had good anti-pollution performance with easy avoidance of inter-assay cross contamination. Finally, use of the SIAO system for adenovirus detection produced similar results to LightCycler2.0 system assay findings. The amplification plots and Ct values suggested similar amplification plots shapes for adenovirus testing with the SIAO system and with real-time fluorescence PCR testing and commercial instrument post-manual nucleic acid extraction. Collectively, these findings indicate that testing with the SIAO system is virtually equivalent to that of manual extraction with commercial system testing.

Mathematical modeling the pathway of human breast cancer.

In order to understand the mechanism of human breast cancer we use the growth rates of clonal expansion of intermediate cells and mutation rates as parameters and build two-six stage models to fit the age-specific incidence of breast cancers in the surveillance, epidemiology, and end results (SEER) registry. We propose four types of different mechanisms for the human breast cancer and test those mechanisms by Chi-square test. Our results suggest that loss of functions of instability genes is an early event in the tumorigenesis, which is useful for early diagnosis of breast cancer. The clonal expansion of intermediate cells must depend on the hormone expression level of females, which implies that it may be effective for females to receive hormone blocking therapy for breast cancer before their menopause.