Ting Wen

Skin biothermomechanics for medical treatments

Electromagnetic heating, such as microwave, radiofrequency, and laser etc., is widely used in medical treatments. Recent advances in these technologies resulted in remarkable developments of thermal treatments for a multitude of diseases and injuries involving skin tissue. The comprehension of heat transfer and related thermomechanics in skin tissue during these treatments is thus of great importance, and can contribute to the further developments of these medical applications. Biothermomechanics of skin is highly interdisciplinary, involving bioheat transfer, burn damage, biomechanics, and physiology. The aim of this study is to develop a computational approach to examine the heat transfer process, heat-induced mechanical response, as well as the associated pain level, so that the differences among the clinically applied heating modalities can be quantified. In this paper, numerical simulation with the finite difference method (FDM) was used to analyze the temperature, burn damage, and thermal stress distributions in the skin tissue subjected to various thermal treatments. The results showed that the thermomechanical behavior of skin tissue is very complex: blood perfusion has little effect on thermal damage, but a large influence on skin temperature distribution, which, in turn, influences significantly the resulting thermal stress field; for laser heating, the peak temperature is higher for lasers with shorter wavelengths, but the peak is closer to the skin surface; the thermal stress due to laser and microwave heating is mainly limited to the top epidermis layer due to the exponential decrease of heat generation along skin depth; the thin (and commonly overlooked) stratum corneum layer dominates the thermomechanical response of skin tissue.

Portable microfluidic and smartphone-based devices for monitoring of cardiovascular diseases at the point of care.

Cardiovascular diseases (CVDs) are the main causes of morbidity and mortality in the world where about 4 in every 5 CVD deaths happen in low- and middle-income countries (LMICs). Most CVDs are preventable and curable, which is largely dependent on timely and effective interventions, including diagnosis, prognosis and therapeutic monitoring. However, these interventions are high-cost in high income countries and are usually lacking in LMICs. Thanks to the rapid development of microfluidics and nanotechnology, lots of portable analytical devices are developed for detection of CVDs at the point-of-care (POC). In the meantime, smartphone, as a versatile and powerful handheld tool, has been employed not only as a reader for microfluidic assays, but also as an analyzer for physiological indexes. In this review, we present a comprehensive introduction of the current status and potential development direction on POC diagnostics for CVDs. First of all, we introduce some main facts about CVDs and their standard diagnostic procedures and methods. Second, we discuss about both commercially available POC devices and developed prototypes for detection of CVDs via immunoassays. Subsequently, we report the advances in smartphone-based readout for microfluidic assays. Finally, we present some examples using smartphone, individually or combined with other components or devices, for CVD monitoring. We envision an integrated smartphone-based system capable of functioning blood tests, disease examination, and imaging will come in the future.

Household Fluorescent Lateral Flow Strip Platform for Sensitive and Quantitative Prognosis of Heart Failure Using Dual-Color Upconversion Nanoparticles

Heart failure (HF) is the end-stage of cardiovascular diseases, which is associated with a high mortality rate and high readmission rate. Household early diagnosis and real-time prognosis of HF at bedside are of significant importance. Here, we developed a highly sensitive and quantitative household prognosis platform (termed as UC-LFS platform), integrating a smartphone-based reader with multiplexed upconversion fluorescent lateral flow strip (LFS). Dual-color core-shell upconversion nanoparticles (UCNPs) were synthesized as probes for simultaneously quantifying two target antigens associated with HF, i.e., brain natriuretic peptide (BNP) and suppression of tumorigenicity 2 (ST2). With the fluorescent LFS, we achieved the specific detection of BNP and ST2 antigens in spiked samples with detection limits of 5 pg/mL and 1 ng/mL, respectively, both of which are of one order lower than their clinical cutoff. Subsequently, a smartphone-based portable reader and an analysis app were developed, which could rapidly quantify the result and share prognosis results with doctors. To confirm the usage of UC-LFS platform for clinical samples, we detected 38 clinical serum samples using the platform and successfully detected the minimal concentration of 29.92 ng/mL for ST2 and 17.46 pg/mL for BNP in these clinical samples. Comparing the detection results from FDA approved clinical methods, we obtained a good linear correlation, indicating the practical reliability and stability of our developed UC-LFS platform. Therefore, the developed UC-LFS platform is demonstrated to be highly sensitive and specific for sample-to-answer prognosis of HF, which holds great potential for risk assessment and health monitoring of post-treatment patients at home.

Polydimethylsiloxane-Paper Hybrid Lateral Flow Assay for Highly Sensitive Point-of-Care Nucleic Acid Testing

In nucleic acid testing (NAT), gold nanoparticle (AuNP)-based lateral flow assays (LFAs) have received significant attention due to their cost-effectiveness, rapidity, and the ability to produce a simple colorimetric readout. However, the poor sensitivity of AuNP-based LFAs limits its widespread applications. Even though various efforts have been made to improve the assay sensitivity, most methods are inappropriate for integration into LFA for sample-to-answer NAT at the point-of-care (POC), usually due to the complicated fabrication processes or incompatible chemicals used. To address this, we propose a novel strategy of integrating a simple fluidic control strategy into LFA. The strategy involves incorporating a piece of paper-based shunt and a polydimethylsiloxane (PDMS) barrier to the strip to achieve optimum fluidic delays for LFA signal enhancement, resulting in 10-fold signal enhancement over unmodified LFA. The phenomena of fluidic delay were also evaluated by mathematical simulation, through which we found the movement of fluid throughout the shunt and the tortuosity effects in the presence of PDMS barrier, which significantly affect the detection sensitivity. To demonstrate the potential of integrating this strategy into a LFA with sample-in-answer-out capability, we further applied this strategy into our prototype sample-to-answer LFA to sensitively detect the Hepatitis B virus (HBV) in clinical blood samples. The proposed strategy offers great potential for highly sensitive detection of various targets for wide application in the near future.

Lateral Flow Assay Based on Paper-Hydrogel Hybrid Material for Sensitive Point-of-Care Detection of Dengue Virus.

Paper-based devices have been broadly used for the point-of-care detection of dengue viral nucleic acids due to their simplicity, cost-effectiveness, and readily observable colorimetric readout. However, their moderate sensitivity and functionality have limited their applications. Despite the above-mentioned advantages, paper substrates are lacking in their ability to control fluid flow, in contrast to the flow control enabled by polymer substrates (e.g., agarose) with readily tunable pore size and porosity. Herein, taking the benefits from both materials, the authors propose a strategy to create a hybrid substrate by incorporating agarose into the test strip to achieve flow control for optimal biomolecule interactions. As compared to the unmodified test strip, this strategy allows sensitive detection of targets with an approximately tenfold signal improvement. Additionally, the authors showcase the potential of functionality improvement by creating multiple test zones for semi-quantification of targets, suggesting that the number of visible test zones is directly proportional to the target concentration. The authors further demonstrate the potential of their proposed strategy for clinical assessment by applying it to their prototype sample-to-result test strip to sensitively and semi-quantitatively detect dengue viral RNA from the clinical blood samples. This proposed strategy holds significant promise for detecting various targets for diverse future applications.

Improved Analytical Sensitivity of Lateral Flow Assay using Sponge for HBV Nucleic Acid Detection

Hepatitis B virus (HBV) infection is a serious public health problem, which can be transmitted through various routes (e.g., blood donation) and cause hepatitis, liver cirrhosis and liver cancer. Hence, it is necessary to do diagnostic screening for high-risk HBV patients in these transmission routes. Nowadays, protein-based technologies have been used for HBV testing, which however involve the issues of large sample volume, antibody instability and poor specificity. Nucleic acid hybridization-based lateral flow assay (LFA) holds great potential to address these limitations due to its low-cost, rapid, and simple features, but the poor analytical sensitivity of LFA restricts its application. In this study, we developed a low-cost, simple and easy-to-use method to improve analytical sensitivity by integrating sponge shunt into LFA to decrease the fluid flow rate. The thickness, length and hydrophobicity of the sponge shunt were sequentially optimized, and achieved 10-fold signal enhancement in nucleic acid testing of HBV as compared to the unmodified LFA. The enhancement was further confirmed by using HBV clinical samples, where we achieved the detection limit of 103 copies/ml as compared to 104 copies/ml in unmodified LFA. The improved LFA holds great potential for diseases diagnostics, food safety control and environment monitoring at point-of-care.

Pen-on-paper strategy for point-of-care testing: Rapid prototyping of fully written microfluidic biosensor

Paper-based microfluidic biosensors have recently attracted increasing attentions in point-of-care testing (POCT) territories benefiting from their affordable, accessible and eco-friendly features, where technologies for fabricating such biosensors are preferred to be equipment free, easy-to-operate and capable of rapid prototyping. In this work, we developed a pen-on-paper (PoP) strategy based on two custom-made pens, i.e., a wax pen and a conductive-ink pen, to fully write paper-based microfluidic biosensors through directly writing both microfluidic channels and electrodes. Particularly, the proposed wax pen is competent to realize one-step fabrication of wax channels on paper, as the melted wax penetrates into paper during writing process without any post-treatments. The practical applications of the fabricated paper-based microfluidic biosensors are demonstrated by both colorimetric detection of Salmonella typhimurium DNA with detection limit of 1nM and electrochemical measurement of glucose with detection limit of 1mM. The developed PoP strategy for making microfluidic biosensors on paper characterized by true simplicity, prominent portability and excellent capability for rapid prototyping shows promising prospect in POCT applications.

Improved LFIAs for highly sensitive detection of BNP at point-of-care

Heart failure (HF) has become a major cause of morbidity and mortality with a significant global economic burden. Although well-established clinical tests could provide early diagnosis, access to these tests is limited in developing countries, where a relatively higher incidence of HF is present. This has prompted an urgent need for developing a cost-effective, rapid and robust diagnostic tool for point-of-care (POC) detection of HF. Lateral flow immunoassay (LFIA) has found widespread applications in POC diagnostics. However, the low sensitivity of LFIA limits its ability to detect important HF biomarkers (e.g., brain natriuretic peptide [BNP]) that are normally present in low concentration in blood. To address this issue, we developed an improved LFIA by optimizing the gold nanoparticle (GNP)–antibody conjugate conditions (e.g., the conjugate pH and the amount of added antibody), the diameter of GNP and the concentration of antibody embedded on the test line and modifying the structure of test strip. Through these improvements, the proposed test strip enabled the detection of BNP down to 0.1 ng/mL within 10–15 min, presenting ~15-fold sensitivity enhancement over conventional lateral flow assay. We also successfully applied our LFIA in the analysis of BNP in human serum samples, highlighting its potential use for clinical assessment of HF. The developed LFIA for BNP could rapidly rule out HF with the naked eye, offering tremendous potential for POC test and personalized medicine.

Capillary blood for point-of-care testing

Abstract Clinically, blood sample analysis has been widely used for health monitoring. In hospitals, arterial and venous blood are utilized to detect various disease biomarkers. However, collection methods are invasive, painful, may result in injury and contamination, and skilled workers are required, making these methods unsuitable for use in a resource-limited setting. In contrast, capillary blood is easily collected by a minimally invasive procedure and has excellent potential for use in point-of-care (POC) health monitoring. In this review, we first discuss the differences among arterial blood, venous blood, and capillary blood in terms of the puncture sites, components, sample volume, collection methods, and application areas. Additionally, we review the most recent advances in capillary blood-based commercial products and microfluidic instruments for various applications. We also compare the accuracy of microfluidic-based testing with that of laboratory-based testing for capillary blood-based disease diagnosis at the POC. Finally, we discuss the challenges and future perspectives for developing capillary blood-based POC instruments.

Geometric Optimization of 2D Cellular Metals Cooled by Forced Convection Subjected to Fixed Pumping Power, Pressure Drop or Mass Flowrate

An analytical approach for the optimal design of 2D cellular metallic structures for heat sink applications is proposed. By integrating fin analogy model into intersection-of-asymptotes method, both the conjugate conduction-convection heat transfer mechanism and the developing flow/temperature fields are considered in this approach. Results are reported nondimensionally for three different flow configurations: fixed mass flowrate, fixed pressure drop and fixed pumping power.