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Simple Summary: Solitary fibrous tumors (SFTs) are tumors that can vary greatly in how they behave, with some being harmless while others become aggressive and life-threatening. This study evaluated 52 fusion-confirmed SFTs with clinical follow-up. The aim was to analyze the immune intratumoral infiltrate and correlate the presence of specific immune cells and risk stratification systems to see if the presence or absence of certain cells could help predict how the tumor will behave or correlate with other clinicopathologic characteristics. The research found that, while certain immune cells were associated with specific tumor features with prognostic significance, these immune cells did not reliably predict the tumor's overall risk level. This suggests that the immune environment within SFTs is complex and may not be useful on its own for determining the tumor progression risk. Nonetheless, the presented results give an insight into the relationship between immune tumor cells and histologic characteristics such as necrosis, proliferation index, and neoplastic cell morphology. Background and objectives: Solitary fibrous tumors (SFTs) are morphologically heterogeneous tumors characterized by the NAB2::STAT6 gene fusion. Clinical outcomes may vary widely, and while most cases have favorable outcomes, some can progress to aggressive disease, manifesting as recurrence and metastasis, and ultimately resulting in patient death. Herein, we analyze the immunological tumor microenvironment (ITME) of SFTs, aiming to determine its prognostic value and correlation with established risk stratification systems (RSSs). Methods: A retrospective observational multicenter study of 52 fusion-confirmed SFTs with clinical follow-up data. Immunohistochemical analysis including CD163, CD68, CD3, CD8, CD20, PDL-1, PD-1, and LAG1 were evaluated in tissue microarrays, using an analog scale with scores ranging from 0 to 3 (0 = ≤9, 1 = 10–49, 2 = 50–99, and 3 = >100 positive cells per 10 high-power fields). The expression of these markers was correlated with clinical outcomes, morphological characteristics previously evaluated in whole slide tissue sections (hypercellularity/hypocellularity, round–oval or spindle dominant constituent cell (DCC) morphology, and necrosis), Ki67, overall survival, and RSS. Results: Only one of the fifty-two cases studied showed progression. In the multivariate analysis, neither the presence nor absence of immune cells (B-lymphocytes, T-lymphocytes, and macrophages) showed any association with the assessed RSSs (Demicco, Sugita, G-score, and Huang). Interestingly, the case that showed progression had high immune infiltrate with expression of CD68, CD163, CD8, and CD20 markers (score of 3). Round–oval cell morphology was associated with the presence of higher levels of CD163 macrophages. Lastly, the scant presence of CD20+ lymphocytes correlated with less necrosis, and cases with higher PDL-1 expression correlated with increased Ki67 values. All cases were negative for LAG-1 and PD-1. Conclusions: SFT ITME components correlated with independent variables with prognostic significance. Nevertheless, ITME did not correlate with RSS scores. [ABSTRACT FROM AUTHOR]

Simple Summary: This study explores whether Escherichia coli carrying the polyketide synthetase (pks) gene cluster in colorectal cancer (CRC) liver metastasis tissues influence immune responses and cancer recurrence patterns. Analyzing tissues from 239 patients, we found that pks+ E. coli was present in 66.7% of liver metastasis cases. Higher levels of pks+ E. coli were associated with lower levels of the serum C-reactive protein, fewer densities of CD4+ cells and CD163+ cells in the tumor microenvironment, and a reduction in the number of organs affected by recurrent metastasis. These findings suggest that pks+ E. coli may influence both systemic and local immune responses, potentially reducing the diversity of affected metastatic organs. Colibactin, a genotoxin produced by Escherichia coli strains harboring the polyketide synthetase (pks) gene cluster, causes DNA damage and somatic mutations. pks+ E. coli is enriched in primary colorectal cancer (CRC) and is associated with clonal driver mutations, but its role in CRC liver metastasis is unclear. We assessed the association of pks+ E. coli in CRC liver metastasis tissues with systemic and local immune responses and the number of organs involved in recurrence using specimens and clinicopathological data from 239 patients with CRC liver metastasis who underwent metastasectomy. The levels of pks+ E. coli in fresh-frozen specimens were quantified as "very low" (<50th percentile), "low" (50th to 75th percentiles), and "high" (>75th percentile) using a digital PCR. Immunohistochemical analysis of tumor-infiltrating immune cells was performed using tissue microarrays. Systemic inflammation was evaluated using serum C-reactive protein (CRP) levels. pks+ E. coli was detected in 66.7% (157 of 239) liver metastasis tissues. Higher levels of pks+E. coli were associated with decreased serum CRP levels and reduced densities of CD4+ cells and CD163+ cells in the tumor-immune microenvironment. The "high" pks+ E. coli group had fewer metastatic organs involved than the "very low" pks+ E. coli group (mean number of organs: 1.00 vs. 1.23). These findings suggest that pks+ E. coli play a modulating role in CRC metastasis. [ABSTRACT FROM AUTHOR]

Flow-based microfluidic biochips (FMBs) are widely used in biomedical research and diagnostics. However, their security against potential material-level cyber-physical attacks remains inadequately explored, posing a significant future challenge. One of the main components, polydimethylsiloxane (PDMS) microvalves, is pivotal to FMBs' functionality. However, their fabrication, which involves thermal curing, makes them susceptible to chemical tampering-induced material degradation attacks. Here, we demonstrate one such material-based attack termed “BioTrojans,” which are chemically tampered and optically stealthy microvalves that can be ruptured through low-frequency actuations. To chemically tamper with the microvalves, we altered the associated PDMS curing ratio. Attack demonstrations showed that BioTrojan valves with 30:1 and 50:1 curing ratios ruptured quickly under 2 Hz frequency actuations, while authentic microvalves with a 10:1 ratio remained intact even after being actuated at the same frequency for 2 days (345,600 cycles). Dynamic mechanical analyzer (DMA) results and associated finite element analysis revealed that a BioTrojan valve stores three orders of magnitude more mechanical energy than the authentic one, making it highly susceptible to low-frequency-induced ruptures. To counter BioTrojan attacks, we propose a security-by-design approach using smooth peripheral fillets to reduce stress concentration by over 50% and a spectral authentication method using fluorescent microvalves capable of effectively detecting BioTrojans. [ABSTRACT FROM AUTHOR]

Simple Summary: The development and use of migrastatic drugs could help improve the outcomes for patients with high-grade non-muscle-invasive bladder cancer and muscle-invasive bladder cancer by inhibiting bladder cancer cell invasion and thereby decreasing the likelihood of disease progression and metastasis. A key barrier to this is the lack of suitable models to assess bladder cancer cell invasiveness. Here, we describe a bladder cancer-on-a-chip model. We demonstrate that our model supports the retention of the bladder cancer cell phenotype and can be used to reproducibly assess and quantify the invasiveness of live bladder cancer cells. Treatment with ATN-161, a well-known migrastatic drug, caused a dose-dependent decrease in bladder cancer cell invasiveness thereby validating the ability of our model to test migrastatic drugs. To our knowledge, a bladder cancer-on-a-chip model that can specifically assess bladder cancer invasiveness has not previously been described. We have developed a bladder cancer-on-a-chip model which supports the 3D growth of cells and can be used to assess and quantify bladder cancer cell invasiveness in a physiologically appropriate environment. Three bladder cancer cell lines (T24, J82, and RT4) were resuspended in 50% Matrigel® and grown within a multi-channel organ-on-a-chip system. The ability of live cells to invade across into an adjacent 50% Matrigel®-only channel was assessed over a 2-day period. Cell lines isolated from patients with high-grade bladder cancer (T24 and J82) invaded across into the Matrigel®-only channel at a much higher frequency compared to cells isolated from a patient with low-grade cancer (RT4) (p < 0.001). The T24 and J82 cells also invaded further distances into the Matrigel®-only channel compared to the RT4 cells (p < 0.001). The cell phenotype within the model was maintained as assessed by cell morphology and immunohistochemical analysis of E-cadherin. Treatment with ATN-161, an α5β1 integrin inhibitor and well-known migrastatic drug, caused a dose-dependent decrease in the invasiveness of the J82 cells (p < 0.01). The combined data demonstrate that our bladder cancer-on-a-chip model supports the retention of the bladder cancer cell phenotype and can be used to reproducibly assess and quantify the invasiveness of live bladder cancer cells. [ABSTRACT FROM AUTHOR]

Most extrauterine high-grade serous carcinomas (HGSCs) are thought to develop first in the distal fallopian tube. Most models of HGSC assume origin from relatively stable, noninvasive serous tubal intraepithelial carcinomas. However, widespread tumor involvement in the absence of a serous tubal intraepithelial carcinoma could occur after catastrophic genomic events (CGEs; such as chromothripsis or polyploidy). Twenty-six HGSCs assigned to fallopian tube (n = 9, group 1) and/or ovary (n = 9, group 2), and primary peritoneal (n = 8, group 3) were assessed by microarray (Oncoscan). CGEs were identified in 15/26 (57.7%); chromothripsis-like pattern in 13/26 (50.0%) and polyploidy in 6/26 (23.1%). CGE was seen in 4/9 (44.4%), 9/9 (100%), and 2/8 (25%) cases in groups 1. 2, and 3, respectively. Overall, CGEs were seen in 9/9 (100%) cases with grossly evident ovarian parenchymal involvement versus 6/17 (35.3%) without (P = 0.0024). Ovarian size (measured on the long axis) correlated with CGE positivity (P = 0.016). CGEs are significantly more common in HGSCs with ovarian parenchymal involvement compared with those limited to the fallopian tube and/or extraovarian tissues. These associations suggest geographically different tumor growth patterns and support the subdivision of HGSCs according to not only the stage but also tumor distribution. They have implications for clinical and pathologic presentation, trajectory of tumor evolution, and in the case of primary peritoneal HGSCs, potentially unique precursors to tumor transitions that could inform or influence cancer prevention efforts. [ABSTRACT FROM AUTHOR]

Abstract Flow-based microfluidic biochips (FMBs) are widely used in biomedical research and diagnostics. However, their security against potential material-level cyber-physical attacks remains inadequately explored, posing a significant future challenge. One of the main components, polydimethylsiloxane (PDMS) microvalves, is pivotal to FMBs' functionality. However, their fabrication, which involves thermal curing, makes them susceptible to chemical tampering-induced material degradation attacks. Here, we demonstrate one such material-based attack termed “BioTrojans,” which are chemically tampered and optically stealthy microvalves that can be ruptured through low-frequency actuations. To chemically tamper with the microvalves, we altered the associated PDMS curing ratio. Attack demonstrations showed that BioTrojan valves with 30:1 and 50:1 curing ratios ruptured quickly under 2 Hz frequency actuations, while authentic microvalves with a 10:1 ratio remained intact even after being actuated at the same frequency for 2 days (345,600 cycles). Dynamic mechanical analyzer (DMA) results and associated finite element analysis revealed that a BioTrojan valve stores three orders of magnitude more mechanical energy than the authentic one, making it highly susceptible to low-frequency-induced ruptures. To counter BioTrojan attacks, we propose a security-by-design approach using smooth peripheral fillets to reduce stress concentration by over 50% and a spectral authentication method using fluorescent microvalves capable of effectively detecting BioTrojans.

Single‐cell multiomic and exosome analyses are potent tools in various fields, such as cancer research, immunology, neuroscience, microbiology, and drug development. They facilitate the in‐depth exploration of biological systems, providing insights into disease mechanisms and aiding in treatment. Single‐cell isolation, which is crucial for single‐cell analysis, ensures reliable cell isolation and quality control for further downstream analyses. Microfluidic chips are small lightweight systems that facilitate efficient and high‐throughput single‐cell isolation and real‐time single‐cell analysis on‐ or off‐chip. Therefore, most current single‐cell isolation and analysis technologies are based on the single‐cell microfluidic technology. This review offers comprehensive guidance to researchers across different fields on the selection of appropriate microfluidic chip technologies for single‐cell isolation and analysis. This review describes the design principles, separation mechanisms, chip characteristics, and cellular effects of various microfluidic chips available for single‐cell isolation. Moreover, this review highlights the implications of using this technology for subsequent analyses, including single‐cell multiomic and exosome analyses. Finally, the current challenges and future prospects of microfluidic chip technology are outlined for multiplex single‐cell isolation and multiomic and exosome analyses. [ABSTRACT FROM AUTHOR]

We introduce a novel approach for highly parallel droplet dispensing with precise control over the droplet parameters such as droplet volume, droplet velocity, etc. This approach facilitates the fabrication of homogeneous and precise thin layers with uniform coverage on defined small areas (e.g., a specific area of 1 × 1.4 mm2 in microfluidic channels or microwells). The presented approach ensures layer uniformity and high precision in X/Y extent and edge resolution, making it well suited for achieving precise and controlled coating for a variety of applications such as homogeneous coatings for lateral flow tests, ELISA plates, and biosensors for continuous glucose monitoring (CGM) devices. Our approach is based on direct liquid displacement employing a piston that is in direct contact with the liquid and an array of nozzles. Considering a variety of nozzle chip designs (i.e., varying nozzle diameter and pitch), we evaluated a multitude of parameters to derive general design rules for the nozzle chip design. Thus, we achieved a tunable droplet volume from 200 to 800 pL and droplet velocities from 0.5 to 2.5 m/s, applying a nozzle diameter of 50 μm and a nozzle pitch of 165 μm. The presented results showcase the versatility of the approach, offering precise dispensing capabilities. [ABSTRACT FROM AUTHOR]

A method has been developed for manufacturing biological microchips on an aluminum substrate with hydrophilic cells from brush copolymers with the formation of a matrix of cells using photolithography. The surface of aluminum substrates was previously coated with a thin, durable, moderately hydrophobic layer of cross-linked polymer to prevent contact with the aluminum surface of the components used in the analysis of nucleic acids. Aluminum biochip substrates have high thermal conductivity and low heat capacity, which is important for the development of methods for multiplex PCR analysis on a chip. Oligonucleotide probes were covalently immobilized in the cells of the biochip. The preservation of the hybridization activity of the immobilized DNA probes was demonstrated in a hybridization analysis with a synthetic DNA target representing a section of the sequence of the seventh exon of the human ABO gene. The methods developed can be used in the development of a technology for parallel multiple rapid microanalysis of nucleic acids "lab on a chip" for the detection of human somatic and infectious diseases. [ABSTRACT FROM AUTHOR]

A wide variety of biomaterials has been developed to assist in wound healing, including acellular animal and human‐derived protein matrices. However, millions of patients worldwide still suffer from non‐healing chronic wounds, demonstrating a need for further innovation in wound care. To address this need, a novel biomaterial, the human keratin matrix (HKM), was developed, characterised, and tested in vitro and in vivo. HKM was found to be degradation‐resistant, and a proteomics analysis showed it to be greater than 99% human keratin proteins. PCR revealed adult human epidermal keratinocytes (HEKa) grown in contact with HKM showed increased gene expression of keratinocyte activations markers such as Epidermal Growth Factor (EGF). Additionally, a cytokine microarray demonstrated culture on HKM increased the release of cytokines involved in wound inflammatory modulation by both HEKa cells and adult human dermal fibroblasts (HDFa). Finally, in a murine chronic wound model, full‐thickness wounds treated weekly with HKM were smaller through the healing process than those treated with human amniotic membrane (AM), bovine dermis (BD), or porcine decellularized small intestinal submucosa (SIS). HKM‐treated wounds also closed significantly faster than AM‐ and SIS‐treated wounds. These data suggest that HKM is an effective novel treatment for chronic wounds. [ABSTRACT FROM AUTHOR]

Simple Summary: The advancement of multidisciplinary treatment has increased the need to develop a test to monitor tumor burden during treatment. We herein analyzed urinary microRNAs within extracellular vesicles from patients with esophageal squamous cell carcinoma (ESCC) and normal individuals using a microarray, and identified 18 microRNAs which were significantly expressed in ESCC patients. Background: The advancement of multidisciplinary treatment has increased the need to develop tests to monitor tumor burden during treatment. We herein analyzed urinary microRNAs within extracellular vesicles from patients with esophageal squamous cell carcinoma (ESCC) and normal individuals using a microarray. Methods: Patients with advanced ESCC who underwent esophagectomy (A), endoscopic submucosal resection (ESD) (B), and healthy donors (C) were included. Based on microRNA expression among the groups (Analysis 1), microRNAs with significant differences between groups A and C were selected (Analysis 2). Of these candidates, microRNAs in which the change between A and C was consistent with the change between B and C were selected for downstream analysis (Analysis 3). Finally, microRNA expression was validated in patients with recurrence from A (exploratory analysis). Results: For analysis 1, 205 microRNAs were selected. For Analyses 2 and 3, the changes in 18 microRNAs were consistent with changes in tumor burden as determined by clinical imaging and pathological findings. The AUC for the detection of ESCC using 18 microRNAs was 0.72. In exploratory analysis, three of eighteen microRNAs exhibited a concordant trend with recurrence. Conclusions: The current study identified the urinary microRNAs which were significantly expressed in ESCC patients. Validation study is warranted to evaluate whether these microRNAs could reflect tumor burden during multidisciplinary treatment for ESCC. [ABSTRACT FROM AUTHOR]

Microfluidic-based biochip is a prominent class of lab-on-a-chip systems for the healthcare, biomedical, and biochemical industries, and was recently used for the detection of the Covid-19 pandemic. This paper is a survey of current attack models in different proactive and reactive remedial actions. Finally, this paper also aims at future directions for researchers to work towards enhancing security and privacy challenges in state-of-the-art microfluidic biochips. [ABSTRACT FROM AUTHOR]

The integration of biochips with AI opened up new possibilities and is expected to revolutionize smart healthcare tools within the next five years. The combination of miniaturized, multi-functional, rapid, high-throughput sample processing and sensing capabilities of biochips, with the computational data processing and predictive power of AI, allows medical professionals to collect and analyze vast amounts of data quickly and efficiently, leading to more accurate and timely diagnoses and prognostic evaluations. Biochips, as smart healthcare devices, offer continuous monitoring of patient symptoms. Integrated virtual assistants have the potential to send predictive feedback to users and healthcare practitioners, paving the way for personalized and predictive medicine. This review explores the current state-of-the-art biochip technologies including gene-chips, organ-on-a-chips, and neural implants, and the diagnostic and therapeutic utility of AI-assisted biochips in medical practices such as cancer, diabetes, infectious diseases, and neurological disorders. Choosing the appropriate AI model for a specific biomedical application, and possible solutions to the current challenges are explored. Surveying advances in machine learning models for biochip functionality, this paper offers a review of biochips for the future of biomedicine, an essential guide for keeping up with trends in healthcare, while inspiring cross-disciplinary collaboration among biomedical engineering, medicine, and machine learning fields.

Introduction: Many organizations are developing new contraceptive products and approaches that promote self-care including a microarray patch (MAP) that has the potential for self-administration with appropriate training. We studied women's perceptions of the MAP technology with the primary goal of providing feedback on product attributes to inform early technical design decisions regarding various MAP contraceptive products in development by MAP developers. Methods: Our study consisted of a qualitative phase with in-person In-Depth Interviews (IDIs) with a total of 60 women of reproductive age (WRA) and quantitative surveys, via face-to-face computer-assisted interviews of a total of 927 women in Ghana, Kenya and Uganda. Women's perceptions on 12 attributes of the MAP were assessed through written descriptions, a profile, and visual stimuli such as graphics and images. Results: Overall, the most widely preferred attribute set included: a hand-applied MAP, utilizing one circular patch, with a sticky backing, no larger than 2 cm diameter in size, applied by self, to the arm, offering sensory feedback (clicking sound and/or color change signals) to confirm enough pressure, successful application and removal, lasting 6 months with up to 12 months return to natural state of fertility. There is space to allow for variation in MAP designs (including the use of an applicator or provider administered MAP) if the design promotes and reflects the needs and expectations of users and providers. Discussion: The contraceptive MAP had a high and broad level of appeal amongst all groups of women who participated in the study and has a strong value proposition around important contraceptive needs such as ease of use, convenience, and discretion. [ABSTRACT FROM AUTHOR]

Micro Electrodes Dot Array (MEDA) based biochips are emerging microdroplets handling technology that empowers supervised fluids governance on a set of microelectrodes. The MEDA-based architecture enables the dynamic routing of droplets with variable sizes for better accuracy and convenience. Efficient droplet routing with prevention of cross-contamination and maintaining all fluidic restriction is the key challenging area on the MEDA-based biochips. We use a two-stage method that involves global and detailed routing. In order to determine the route capacity of every feasible routing path for each droplet, a graph denoting the capacity has been created during the global routing phase. The proposed method assigns the priority of each net depending on the influence factors of the other nets and blockages present in the bioassay. The proposed approach enables 80% of droplet routing without any cross-contamination, based on the First Priority Movement (FPM) and Second Priority Movement (SPM) in the first stage. A capacity graph provides maximum droplets flow using FPM and finds the suitable channel to reshape the size of the droplets to avoid collision on the routing paths to accomplish 100% routing. Experimental results demonstrate that even in complex bio-assays, our proposed phase-wise router reduces 20% of the latest arrival time (Tla) and minimizes 9% average time (Tavg) by decreasing 15% of microelectrodes count compared to other routing protocols. [ABSTRACT FROM AUTHOR]

Biological assays around "lab-on-a-chip (LoC)" are required in multiple concentration (or dilution) factors, satisfying specific sample concentrations. Unfortunately, most of them suffer from non-locality and are non-protectable, requiring a large footprint and high purchase cost. A digital geometric technique can generate arbitrary gradient profiles for digital microfluidic biochips (DMFBs). A next- generation DMFB has been proposed based on the microelectrode-dot-array (MEDA) architectures are shown to produce and disperse droplets by channel dispensing and lamination mixing. Prior work in this area must address the problem of reactant and waste minimization and concurrent sample preparation for multiple target concentrations. This paper proposes the first splitting-droplet sharing algorithm for reactant and waste minimization of multiple target concentrations on MEDAs. The proposed algorithm not only minimizes the consumption of reagents but also reduces the number of waste droplets by preparing the target concentrations concurrently. Experimental results on a sequence of exponential gradients are presented in support of the proposed method and demonstrate its effectiveness and efficiency. Compared to prior work, the proposed algorithm can achieve up to a 24.8% reduction in sample usage and reach an average of 50% reduction in waste droplets. [ABSTRACT FROM AUTHOR]

Simple Summary: Protein Tyrosine Phosphatase Receptor Type D (PTPRD) plays a role in cell proliferation, differentiation, oncogenic transformation, and brain development and serves as an orexigenic asprosin receptor. This study investigates the expression of PTPRD in endometrial cancer (EC) and the placenta, as well as in glioblastoma (GBM). PTPRD is significantly upregulated at the mRNA and protein levels in patients with EC and GBM compared to healthy controls. In patients with EC, PTPRD is significantly downregulated by obesity. Using a tissue microarray, abundant PTPRD expression in low- and high-grade EC tumours is noted. Using liquid biopsies from EC patients, we show the expression of PTPRD in peripheral leukocytes. Moreover, asprosin treatment upregulates the expression of PTPRD in syncytialised placental cells in vitro, but not in EC cell lines. Collectively, our data suggest that PTPRD may have potential as a biomarker for malignancies such as EC and GBM, further implicating asprosin as a potential metabolic regulator in these cancers. Background: Protein Tyrosine Phosphatase Receptor Type D (PTPRD) is involved in the regulation of cell growth, differentiation, and oncogenic transformation, as well as in brain development. PTPRD also mediates the effects of asprosin, which is a glucogenic hormone/adipokine derived following the cleavage of the C-terminal of fibrillin 1. Since the asprosin circulating levels are elevated in certain cancers, research is now focused on the potential role of this adipokine and its receptors in cancer. As such, in this study, we investigated the expression of PTPRD in endometrial cancer (EC) and the placenta, as well as in glioblastoma (GBM). Methods: An array of in silico tools, in vitro models, tissue microarrays (TMAs), and liquid biopsies were employed to determine the gene and protein expression of PTPRD in healthy tissues/organs and in patients with EC and GBM. Results: PTPRD exhibits high expression in the occipital lobe, parietal lobe, globus pallidus, ventral thalamus, and white matter, whereas in the human placenta, it is primarily localised around the tertiary villi. PTPRD is significantly upregulated at the mRNA and protein levels in patients with EC and GBM compared to healthy controls. In patients with EC, PTPRD is significantly downregulated with obesity, whilst it is also expressed in the peripheral leukocytes. The EC TMAs revealed abundant PTPRD expression in both low- and high-grade tumours. Asprosin treatment upregulated the expression of PTPRD only in syncytialised placental cells. Conclusions: Our data indicate that PTPRD may have potential as a biomarker for malignancies such as EC and GBM, further implicating asprosin as a potential metabolic regulator in these cancers. Future studies are needed to explore the potential molecular mechanisms/signalling pathways that link PTPRD and asprosin in cancer. [ABSTRACT FROM AUTHOR]

Background: The functional heterogeneity of culture-expanded mesenchymal stem cells (MSCs) has hindered the clinical application of MSCs. Previous studies have shown that MSC subpopulations with superior chondrogenic capacity can be isolated using a spiral microfluidic device based on the principle of inertial cell focusing. Hypothesis: The delivery of microfluidic-enriched chondrogenic MSCs that are consistent in size and function will overcome the challenge of the functional heterogeneity of expanded MSCs and will significantly improve MSC-based cartilage repair. Study Design: Controlled laboratory study. Methods: A next-generation, fully automated multidimensional double spiral microfluidic device was designed to provide more refined and efficient isolation of MSC subpopulations based on size. Analysis of in vitro chondrogenic potential and RNA sequencing was performed on size-sorted MSC subpopulations. In vivo cartilage repair efficacy was demonstrated in an osteochondral injury model in 12-week-old rats. Defects were implanted with MSC subpopulations (n = 6 per group) and compared with those implanted with unsegregated MSCs (n = 6). Osteochondral repair was assessed at 6 and 12 weeks after surgery by histological, micro–computed tomography, and mechanical analysis. Results: A chondrogenic MSC subpopulation was efficiently isolated using the multidimensional double spiral device. RNA sequencing revealed distinct transcriptomic profiles and identified differential gene expression between subpopulations. The delivery of a chondrogenic MSC subpopulation resulted in improved cartilage repair, as indicated by histological scoring, the compression modulus, and micro–computed tomography of the subchondral bone. Conclusion: We have established a rapid, label-free, and reliable microfluidic protocol for more efficient size-based enrichment of a chondrogenic MSC subpopulation. Our proof-of-concept in vivo study demonstrates the enhanced cartilage repair efficacy of these enriched chondrogenic MSCs. Clinical Relevance: The delivery of microfluidic-enriched chondrogenic MSCs that are consistent in size and function can overcome the challenge of the functional heterogeneity of expanded MSCs, resulting in significant improvement in MSC-based cartilage repair. The availability of such rapid, label-free enriched chondrogenic MSCs can enable better cell therapy products for cartilage repair with improved treatment outcomes. [ABSTRACT FROM AUTHOR]

A digital microfluidic biochip (DMFB) with cyber-physical adaptation implements complex bio-protocols with high precision and high throughput dealing with safety-critical applications including point-of-care diagnosis, personalized medicine, and drug development. Having integrated sensors with network connectivity, a cyber-physical DMFB is undeniably susceptible to attacks. A number of leading research works are carried out to assess various attacks and their impacts. Several defense mechanisms are developed by arranging on-chip monitoring systems through deployment of checkpoints. As checkpoints are external resources imposing a cost-overhead to the system, a cost-effective detection mechanism is of utmost importance. Moreover, after detecting an attack, an efficient recovery process is imperative to execute the associated bioassay in a vulnerable environment. Here, an attack-tolerant synthesis is proposed with two-way security through integrating attack-detection and attack-recovery from various Denial of Service attacks. Moreover, a selective re-synthesis approach has been introduced to allow multiple recovery steps to be executed simultaneously on the biochip. The recovery strategy is closely coupled with the detection process which makes the system adaptive towards attack-tolerance. Experimental results on several benchmarks demonstrate the efficacy of the proposed two-way attack-tolerance strategy. [ABSTRACT FROM AUTHOR]

In situ monitoring of endogenous amino acid loss through sweat can provide physiological insights into health and metabolism. However, existing amino acid biosensors are unable to quantitatively assess metabolic status during exercise and are rarely used to establish blood-sweat correlations because they only detect a single concentration indicator and disregard sweat rate. Here, we present a wearable multimodal biochip integrated with advanced electrochemical electrodes and multipurpose microfluidic channels that enables simultaneous quantification of multiple sweat indicators, including phenylalanine and chloride, as well as sweat rate. This combined measurement approach reveals a negative correlation between sweat phenylalanine levels and sweat rates among individuals, which further enables identification of individuals at high metabolic risk. By tracking phenylalanine fluctuations induced by protein intake during exercise and normalizing the concentration indicator by sweat rates to reduce interindividual variability, we demonstrate a reliable method to correlate and analyze sweat-blood phenylalanine levels for personal health monitoring. The in-depth study on the sweat–blood partitioning mechanisms of amino acids is promising for noninvasive metabolic monitoring. Here, the authors develop a wearable biochip for sweat phenylalanine multimodal analysis aimed at tracking exercise metabolic risk and exploring the sweat–blood correlation. [ABSTRACT FROM AUTHOR]

With the continuous development of microfluidic technology, continuous-flow microfluidic biochips (CFMBs) are being increasingly used in the Internet of Things. The automation design of CFMBs has also received widespread attention. The architecture design of CFMBs is divided into a high-level synthesis stage and a physical design stage. Among them, the problem of the physical design stage is very complex. At this stage, the chip architecture is generated based on the device library and a set of flow paths, taking into account the actual fluid manipulations, while minimizing the cost of the chip, such as the number of ports, total length of flow channels, number of flow channel intersections. As fabrication technology advances, the number of devices integrated into CFMBs is increasing. The existing physical design algorithms can no longer meet the design requirements of CFMBs in terms of time. Therefore, we propose a three-stage rapid physical design algorithm for CFMBs considering the actual fluid manipulations. The proposed algorithm includes a port-driven preprocessing stage, a force-directed quadratic placement stage, and a negotiation-based routing stage. In the port-driven preprocessing stage, a port-driven preprocessing algorithm is proposed to generate connection matrices between ports and devices to reduce the number of ports introduced. In the force-directed quadratic placement stage, we model the placement problem as an extremum problem of a quadratic cost function, which mathematically reduces the search space significantly and shortens the running time of the algorithm significantly. In the negotiation-based routing stage, a heuristic negotiation-based routing algorithm and a flow channel strategy that prioritizes the construction of parallel execution are proposed to reduce the running time of the algorithm while ensuring that the number of crossings in the routing solution is close to the optimal solution. Experimental results confirm that our proposed method is able to generate the high-quality solutions quickly. Under general scale problems, compared to the existing method based on ILP, our proposed method achieves a speedup ratio of 23,171 in terms of CPU time and optimizations in terms of number of ports and port reuse of 3.18% and 6.52%, respectively. These optimizations come at the cost of only a slight increase in the number of intersections, the flow length, and the number of flow valves. In addition, our proposed method can effectively solve large-scale problems that cannot be solved by existing method based on ILP. [ABSTRACT FROM AUTHOR]

Continuous-flow microfluidic biochips are a type of biochip technology based on microfluidic channels that enable various biological experiments and analyses to be performed on a tiny chip. They have the advantages of a high throughput, high sensitivity, high precision, low cost, and quick response. In the architectural synthesis of continuous-flow microfluidic biochips (CFMBs), prior work has not considered reducing component interconnection requirements, which led to an increase in the number of connection pairs. In this paper, we propose an architectural synthesis flow for continuous-flow microfluidic biochips with connection pair optimization, which includes high-level synthesis, placement, and routing. In the high-level synthesis stage, our method reduces the need for component interconnections, which reduces the number of connection pairs. Our method performs fine-grained binding, ultimately obtaining high-quality binding and scheduling results for flow paths. Based on the high-quality binding results, we propose a port placement strategy based on port correlation and subsequently use a quadratic placer to place the components. During the routing stage, we employ a conflict-aware routing algorithm to generate flow channels to reduce conflicts between liquid transportation tasks. Experimental results on multiple benchmarks demonstrate the effectiveness of our method. Compared with the existing work, the proposed algorithm obtains average reductions of 35.34% in connection pairs, 24.30% in flow channel intersections, 21.71% in total flow channel length, and 18.39% in the execution time of bioassays. [ABSTRACT FROM AUTHOR]

Precise control of the evaporation of multiple droplets on patterned surfaces is crucial in many technological applications, such as anti‐icing, coating, and high‐throughput assays. Yet, the complex evaporation process of multiple droplets on well‐defined patterned surfaces is still poorly understood. Herein, we develop a digital twin system for real‐time monitoring of key processes on a droplet microarray (DMA), which is essential for parallelization and automation of the operations for cell culture. Specifically, we investigate the evaporation of multiple nanoliter droplets under different conditions via experiments and numerical simulations. We demonstrate that the evaporation rate is not only affected by the environmental humidity and temperature but is also strongly linked to the droplet distribution on the patterned surfaces, being significantly reduced when the droplets are densely distributed. Furthermore, we propose a theoretical method to aid in the experimental detection of volumes and pH variation of evaporating droplets on patterned substrates. This versatile and practical strategy allows us to achieve active maneuvering of the collective evaporation of droplets on a DMA, which provides essential implications for a wide range of applications including cell culture, heat management, microreactors, biochips, and so on. [ABSTRACT FROM AUTHOR]

The development of therapeutic interventions for diseases necessitates a crucial step known as drug screening, wherein potential substances with medicinal properties are rigorously evaluated. This process has undergone a transformative evolution, driven by the imperative need for more efficient, rapid, and high-throughput screening platforms. Among these, microfluidic systems have emerged as the epitome of efficiency, enabling the screening of drug candidates with unprecedented speed and minimal sample consumption. This review paper explores the cutting-edge landscape of microfluidic-based drug screening platforms, with a specific emphasis on two pioneering approaches: organ-on-a-chip and C. elegans-based chips. Organ-on-a-chip technology harnesses human-derived cells to recreate the physiological functions of human organs, offering an invaluable tool for assessing drug efficacy and toxicity. In parallel, C. elegans-based chips, boasting up to 60% genetic homology with humans and a remarkable affinity for microfluidic systems, have proven to be robust models for drug screening. Our comprehensive review endeavors to provide readers with a profound understanding of the fundamental principles, advantages, and challenges associated with these innovative drug screening platforms. We delve into the latest breakthroughs and practical applications in this burgeoning field, illuminating the pivotal role these platforms play in expediting drug discovery and development. Furthermore, we engage in a forward-looking discussion to delineate the future directions and untapped potential inherent in these transformative technologies. Through this review, we aim to contribute to the collective knowledge base in the realm of drug screening, providing valuable insights to researchers, clinicians, and stakeholders alike. We invite readers to embark on a journey into the realm of microfluidic-based drug screening platforms, fostering a deeper appreciation for their significance and promising avenues yet to be explored. [ABSTRACT FROM AUTHOR]

In this paper, the data exchange process based on the data sharing and exchange platform accesses the hospital system, generates the sharing and exchange data, and sends the data that passes the inspection to the data center at this level, and does the Utilization of the uploaded data, so as to build the medical information sharing platform. Through the hyper-convergence architecture, data with repetitive and complexity are integrated and consolidated, so as to realize the integration and utilization of information resources centered on the patient’s master index. And biochip technology is applied to monitor the changes of biologically active substances in the patient’s body to realize rapid diagnosis and screening by doctors. The results show that: hyper-converged architecture IOPS peaks at 5981 IOPs, while the peak of traditional minicomputer is only 75 /IOPs. Another key index I/O database operation, hyper-converged architecture I/O peaks at 9834 M/s, an average of 6537 M/s. while Fujitsu minicomputer’s peak is only 108 M/s, an average of 17 M/s. This paper research is full of the hospital’s management and decision-making needs of the hospital, and has a very good promotion prospect. [ABSTRACT FROM AUTHOR]

Cell models are one of the most widely used basic models in biological research, and a variety of in vitro cell culture techniques and models have been developed recently to simulate the physiological microenvironment in vivo. However, regardless of the technique or model, cell culture is the most fundamental but crucial component. As a result, we have developed a cell culture monitoring system to assess the functional status of cells within a biochip. This article focuses on a mini-microscope made from a readily available camera for in situ continuous observation of cell growth within a biochip and a pH sensor based on optoelectronic sensing for measuring pH. With the aid of this monitoring system, scientists can keep an eye on cell growth in real time and learn how the pH of the culture medium affects it. This study offers a new approach for tracking cells on biochips and serves as a valuable resource for enhancing cell culture conditions. [ABSTRACT FROM AUTHOR]

Protein complex assembly facilitates the combination of individual protein subunits into functional entities, and thus plays a crucial role in biology and biotechnology. Recently, we developed quasi-twodimensional, silicon-based compartmental biochips that are designed to study and administer the synthesis and assembly of protein complexes. At these biochips, individual protein subunits are synthesized from locally confined high-density DNA brushes and are captured on the chip surface by molecular traps. Here, we investigate single-gene versions of our quasi-twodimensional synthesis systems and introduce the trap-binding efficiency to characterize their performance. We show by mathematical and computational modeling how a finite trap density determines the dynamics of protein-trap binding and identify three distinct regimes of the trap-binding efficiency. We systematically study how protein-trap binding is governed by the system's three key parameters, which are the synthesis rate, the diffusion constant and the trap-binding affinity of the expressed protein. In addition, we describe how spatially differential patterns of traps modulate the protein-trap binding dynamics. In this way, we extend the theoretical knowledge base for synthesis, diffusion, and binding in compartmental systems, which helps to achieve better control of directed molecular self-assembly required for the fabrication of nanomachines for synthetic biology applications or nanotechnological purposes. [ABSTRACT FROM AUTHOR]

Dermatophytosis is a superficial fungal infection with an ever-increasing number of patients. Culture-based mycology remains the most commonly used diagnosis, but it takes around four weeks to identify the causative agent. Therefore, routine clinical laboratories need rapid, high throughput, and accurate species-specific analytical methods for diagnosis and therapeutic management. Based on these requirements, we investigated the feasibility of DendrisCHIP® technology as an innovative molecular diagnostic method for the identification of a subset of 13 pathogens potentially responsible for dermatophytosis infections in clinical samples. This technology is based on DNA microarray, which potentially enables the detection and discrimination of several germs in a single sample. A major originality of DendrisCHIP® technology is the use of a decision algorithm for probability presence or absence of pathogens based on machine learning methods. In this study, the diagnosis of dermatophyte infection was carried out on more than 284 isolates by conventional microbial culture and DendrisCHIP®DP, which correspond to the DendrisCHIP® carrying oligoprobes of the targeted pathogens implicated in dermatophytosis. While convergence ranging from 75 to 86% depending on the sampling procedure was obtained with both methods, the DendrisCHIP®DP proved to identify more isolates with pathogens that escaped the culture method. These results were confirmed at 86% by a third method, which was either a specific RT-PCR or genome sequencing. In addition, diagnostic results with DendrisCHIP®DP can be obtained within a day. This faster and more accurate identification of fungal pathogens with DendrisCHIP®DP enables the clinician to quickly and successfully implement appropriate antifungal treatment to prevent the spread and elimination of dermatophyte infection. Taken together, these results demonstrate that this technology is a very promising method for routine diagnosis of dermatophytosis. [ABSTRACT FROM AUTHOR]

Digital microfluidic biochips (DMFBs), which are used in various fields like DNA analysis, clinical diagnosis, and PCR testing, have made biochemical experiments more compact, efficient, and user-friendly than the previous methods. However, their reliability is often compromised by their inability to adapt to all kinds of errors. Errors in biochips can be categorized into two types: known errors, and unknown errors. Known errors are detectable before the start of the routing process using sensors or cameras. Unknown errors, in contrast, only become apparent during the routing process and remain undetected by sensors or cameras, which can unexpectedly stop the routing process and diminish the reliability of biochips. This paper introduces a deep reinforcement learning-based routing algorithm, designed to manage not only known errors but also unknown errors. Our experiments demonstrated that our algorithm outperformed the previous ones in terms of the success rate of the routing, in the scenarios including both known errors and unknown errors. Additionally, our algorithm contributed to detecting unknown errors during the routing process, identifying the most efficient routing path with a high probability. [ABSTRACT FROM AUTHOR]

Forensic DNA typing has been widely accepted in the courts all over the world. This is because DNA profiling is a very powerful tool to identify individuals on the basis of their unique genetic makeup. DNA evidence is capable of not only identifying the presence of specific biospecimens in a crime scene, but it is also used to exonerate suspects who are innocent of a crime. Technological advancements in DNA profiling, including the development of validated kits and statistical methods have made this tool to be more precise in forensic investigations. Therefore, validated combined DNA index system (CODIS) short tandem repeats (STRs) kits which require very small amount of DNA, coupled with real-time polymerase chain reaction (PCR) and the statistical strengths are used routinely to identify human remains, establish paternity or to match suspected crime scene biospecimens. The road to modern DNA profiling has been long, and it has taken scientists decades of work and fine tuning to develop highly accurate testing and analyses that are used today. This review will discuss the various DNA polymorphisms and their utility in human identity testing. [ABSTRACT FROM AUTHOR]

We introduce a novel approach for highly parallel droplet dispensing with precise control over the droplet parameters such as droplet volume, droplet velocity, etc. This approach facilitates the fabrication of homogeneous and precise thin layers with uniform coverage on defined small areas (e.g., a specific area of 1 × 1.4 mm2 in microfluidic channels or microwells). The presented approach ensures layer uniformity and high precision in X/Y extent and edge resolution, making it well suited for achieving precise and controlled coating for a variety of applications such as homogeneous coatings for lateral flow tests, ELISA plates, and biosensors for continuous glucose monitoring (CGM) devices. Our approach is based on direct liquid displacement employing a piston that is in direct contact with the liquid and an array of nozzles. Considering a variety of nozzle chip designs (i.e., varying nozzle diameter and pitch), we evaluated a multitude of parameters to derive general design rules for the nozzle chip design. Thus, we achieved a tunable droplet volume from 200 to 800 pL and droplet velocities from 0.5 to 2.5 m/s, applying a nozzle diameter of 50 μm and a nozzle pitch of 165 μm. The presented results showcase the versatility of the approach, offering precise dispensing capabilities.

Flow-based microfluidic biochips (FMBs) have been rapidly commercialized and deployed in recent years for biological computing, clinical diagnostics, and point-of-care-tests (POCTs). However, outsourcing FMBs makes them susceptible to material-level attacks by malicious actors for illegitimate monetary gain. The attacks involve deliberate material degradation of an FMB's polydimethylsiloxane (PDMS) components by either doping with reactive solvents or altering the PDMS curing ratio during fabrication. Such attacks are stealthy enough to evade detection and deteriorate the FMB's function. Furthermore, material-level attacks can become prevalent in attacks based on intellectual property (IP) theft, such as counterfeiting, overbuilding, etc., which involve unscrupulous third-party manufacturers. To address this problem, we present a dynamic material-level watermarking scheme for PDMS-based FMBs with microvalves using a perylene-labeled fluorescent dye. The dyed microvalves show a unique excimer intensity peak under 405 nm laser excitation. Moreover, when pneumatically actuated, the peak shows a predetermined downward shift in intensity as a function of mechanical strain. We validated this protection scheme experimentally using fluorescence microscopy, which showed a high correlation (R2 = 0.971) between the normalized excimer intensity change and the maximum principal strain of the actuated microvalves. To detect curing ratio-based attacks, we adapted machine learning (ML) models, which were trained on the force-displacement data obtained from a mechanical punch test method. Our ML models achieved more than 99% accuracy in detecting curing ratio anomalies. These countermeasures can be used to proactively safeguard FMBs against material-level attacks in the era of global pandemics and diagnostics based on POCTs. [ABSTRACT FROM AUTHOR]

OBJECTIVE The stage of colon cancer (CC) and therefore the level at which the treatment is initiated affects the survival of CC patients. In our study, we aimed to identify the common survival-related genes in both early- and late-stage CC patients. METHODS Information on the demographic characteristics of 581 patients and microarray expression profiles (GSE39582) were obtained from the gene expression omnibus database. Survival analysis was performed using univariate and multivariate Cox regression methods with the help of R3.53 programming language and Kaplan-Meier graphics through the R software "Survival" package. ShinyGO v0.741 gene ontology enrichment analysis was performed to clarify the common and functional pathways related to both early- and late-stage CC cancer patients' data. RESULTS Cox regression analysis indicated that overall survival and relapse-free survival of CC patients were strongly influenced by stage. Genes that significantly affect prognosis and survival in early- and latestage CC patients were identified. As a result of gene enrichment analysis, arginine binding, oxidoreductase activity, and methylcytosine dioxygenase activity and related eight hub genes (TM4SF5, NOS3, Ten eleven translocation [TET1], TET3, JMJD7, AKR1C1, prenylcysteine oxidase 1 like, Methionine sulfoxide reductase A) were identified. CONCLUSION According to our results, it might be considered that developing new treatment strategies based on eight hub-genes related to arginine binding, oxidoreductase activity, and methylcytosine dioxygenase activity detected at different stages of CC might increase the success of targeted therapies. [ABSTRACT FROM AUTHOR]

A method for the photolithographic fabrication of biochips with hydrogel cells made of brush acrylic acid–acrylamide copolymers fixed by one end on the surface of a polymer substrate has been developed. Hydrogel cells with reactive carboxyl groups were used for covalent immobilization of oligonucleotide probes. The efficiency of the method was demonstrated by the hybridization analysis of DNA targets of different lengths, matching a segment of exon 7 of the human ABO gene. [ABSTRACT FROM AUTHOR]

Innovations in implant designs and computer technology have led to the development of smart implants and prostheses in the field of orthopedics and trauma. Sensor-guided devices enable close monitoring of physical, chemical and biological environment around the implants, which has been purported to meliorate the intra-operative precision and post-operative surveillance of patients. We evaluate the current applications of sensor-based technology in the management of patients with a spectrum of musculoskeletal conditions. A thorough search of literature was performed on May 1, 2023, using the 5 databases (Embase, PubMed, Google Scholar, Cochrane Library and Web of Science) in order to identify suitable studies published between 2000 and 2023. All the studies which reported on SMART implants and Sensor based technology in the diverse sub-specialties of orthopedics like trauma, arthroplasty, spine surgery, infections, arthroscopy or sports medicine and paediatric orthopedics were considered. The keywords used for the search included 'Sensor technology', 'SMART implant' and "Orthopedics". Thirty articles were considered for this narrative review. A generation of SMART implants has been developed due to advancements in the microchip technology. Sensor based technology has been utilised in various subspecialties of arthroplasty (in assessing ligament balancing intra-operatively; or prosthetic loosening and gait analysis during follow-up), trauma surgery (as SMART instruments intra-operatively; or in the assessment of bone healing, distraction osteogenesis and functional recovery during follow-up), spine surgery (identification and protection of neural elements from iatrogenic injuries intra-operatively; and assessment of fusion across the instrumented levels during follow-up), paediatric orthopedics (compliance assessment for foot abduction orthosis in congenital talipes equinovarus), infection (monitoring of infection and biofilm formation), rehabilitation (gait analysis) and sports medicine (rotational stability and ligament compliance in patients with ligament injuries or reconstruction). SMART implants and Sensor based technology have applications in the surgical planning, intra-operative performance, post-operative monitoring and patient surveillance diverse subspecialties of orthopedics and trauma. Future research in newer designs, cost-effective SMART implants and refinement of Sensor based technology will enhance Patient Related Outcome Measures (PROMs). [ABSTRACT FROM AUTHOR]

Microfluidics evolved with the appearance of polydimethylsiloxane (PDMS), an elastomer with a short processing time and the possibility for replication on a micrometric scale. Despite the many advantages of PDMS, there are well-known drawbacks, such as the hydrophobic surface, the absorption of small molecules, the low stiffness, relatively high cost, and the difficulty of scaling up the fabrication process for industrial production, creating a need for alternative materials. One option is the use of stiffer thermoplastics, such as the cyclic olefin copolymer (COC), which can be mass produced, have lower cost and possess excellent properties. In this work, a method to fabricate COC microfluidic structures was developed. The work was divided into process optimization and evaluation of material properties for application in microfluidics. In the processing step, moulding, sealing, and liquid handling aspects were developed and optimized. The resulting COC devices were evaluated from the point of view of molecular diffusion, burst pressure, temperature resistance, and susceptibility to surface treatments and these results were compared to PDMS devices. Lastly, a target DNA hybridization assay was performed showing the potential of the COC-based microfluidic device to be used in biosensing and Lab-on-a-Chip applications. [ABSTRACT FROM AUTHOR]

We report on the use of biochips based on one-dimensional photonic crystals sustaining Bloch surface waves to specifically detect target miRNA that is characteristic of hemorrhagic stroke (miR-16-5p) at low concentration in a buffer solution. The biochips were functionalized with streptavidin and ssDNA oligonucleotides to enable miRNA detection. To discriminate the target miRNA from a non-specific control (miR-101a-3p), we made use of an optical platform developed to work both in label-free and fluorescence detection modes. We demonstrate that the limit of detection provided when operating in the fluorescence mode allows us to specifically detect the target miRNA down to 1 ng mL−1 (140 pM), which matches the recommendations for diagnostic miRNA assays, 5 ng mL−1. The low costs open the way towards the application of these disposable optical biochips based on 1DPC sustaining Bloch surface waves as a promising tool for early disease detection in a liquid biopsy format. [ABSTRACT FROM AUTHOR]

Flexible biochips that enable sensitive detection and simultaneous quantification of biomarkers are of great importance in the field of point-of-care testing. Recently, surface-enhanced Raman scattering (SERS)-based flexible biochips have attracted a great deal of research attention for disease detection due to their rapid, sensitive, and noninvasive sensing abilities. Phenomenal progress in the synthesis of structure-controlled plasmonic nanomaterials has made SERS a powerful sensing platform for disease diagnosis and trace detection. Here, we demonstrate flexible plasmonic biochips for the SERS-based detection of uric acid (UA). Flexible strips exhibited excellent sensing performance with a detection limit of around 10 μM of UA, which is lower than the average level of UA in tears. This rapid and sensitive detection method enables the noninvasive diagnosis of gouty arthritis. [ABSTRACT FROM AUTHOR]

Microfluidic biochips are a prominent class of lab-on-a-chip, i.e. LoC system, guided with some activation sequences devised for a bioprotocol to manipulate fluids used in biomedical and biochemical laboratory syntheses. This paper is a survey of reliability issues for state-of-the-art microfluidic biochips. First, this paper presents the basic structure and working principles for different types of available microfluidic biochips. After that, it elaborates on a systematic analysis of security and reliability issues in performing different fluidic operations using microfluidic biochips. This paper also presents the current attack models and types with their scenarios in different remedy actions, both proactive and reactive. Finally, this paper concludes with future research directions so that the effects due to attacks on biochips will be minimized within the stipulated time for a reliable and sustainable microfluidic biochip world. [ABSTRACT FROM AUTHOR]

The goal of the AIDS and Cancer Specimen Resource (ACSR) is to play a major role in the advancement of HIV/AIDS cancer-related research/treatment by providing richly annotated biospecimens and data to researchers at no cost. The ACSR acquires, stores, and equitably distributes these samples and associated clinical data to investigators conducting HIV/AIDS-related research, at no costs. Currently, it is the only biorepository of human biospecimens from people with HIV and cancer available to eligible researchers globally who are studying HIV associated malignancies. This review describes the history and organizational structure of the ACSR, its types of specimens in its inventory, and the process of requesting specimens. In addition, the review provides an overview of research that was performed over the last 5 years with its support and gives a summary of important new findings acquired by this research into the development of cancers in people with HIV, including both Aids-related and non-Aids-related malignancies. [ABSTRACT FROM AUTHOR]

Digital microfluidic biochips are becoming an alternative for laboratory experiments like DNA analysis, immunoassays and safety clinical diagnostics. Reliability is a critical issue for them. MEDA biochips are a new kind of digital microfluidic biochips which are based on microelectrode-dot-array. Daisy chain is the key component of a MEDA biochip, if there is one fault exist in one cell, the whole daisy chain is broken down, the biochip has to be discarded. Therefore, daisy chain's reliability is especially critical. The paper proposes a new daisy chain online repair scheme, where the cells of daisy chain are repaired during the time of the functional data shifted in. The emphasis is on identifying and repairing the fail daisy chain cells when bioassay is running, without any influence on the executing bioassay. Besides, the online self-repair scheme does not contribute to electrode degradation, and takes no additional time. The experimental results also prove the efficiency of the scheme. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to elucidate the presence, antigen specificities, and potential clinical associations of anti–neutrophil extracellular trap (anti‐NET) antibodies in a multinational cohort of antiphospholipid (aPL) antibody–positive patients who did not have lupus. Methods: Anti‐NET IgG/IgM levels were measured in serum samples from 389 aPL‐positive patients; 308 patients met the classification criteria for antiphospholipid syndrome. Multivariate logistic regression with best variable model selection was used to determine clinical associations. For a subset of the patients (n = 214), we profiled autoantibodies using an autoantigen microarray platform. Results: We found elevated levels of anti‐NET IgG and/or IgM in 45% of the aPL‐positive patients. High anti‐NET antibody levels are associated with more circulating myeloperoxidase (MPO)–DNA complexes, which are a biomarker of NETs. When considering clinical manifestations, positive anti‐NET IgG was associated with lesions affecting the white matter of the brain, even after adjusting for demographic variables and aPL profiles. Anti‐NET IgM tracked with complement consumption after controlling for aPL profiles; furthermore, patient serum samples containing high levels of anti‐NET IgM efficiently deposited complement C3d on NETs. As determined by autoantigen microarray, positive testing for anti‐NET IgG was significantly associated with several autoantibodies, including those recognizing citrullinated histones, heparan sulfate proteoglycan, laminin, MPO–DNA complexes, and nucleosomes. Anti‐NET IgM positivity was associated with autoantibodies targeting single‐stranded DNA, double‐stranded DNA, and proliferating cell nuclear antigen. Conclusion: These data reveal high levels of anti‐NET antibodies in 45% of aPL‐positive patients, where they potentially activate the complement cascade. While anti‐NET IgM may especially recognize DNA in NETs, anti‐NET IgG species appear to be more likely to target NET‐associated protein antigens. [ABSTRACT FROM AUTHOR]

Biochips, a novel technology in the field of biomolecular analysis, offer a promising alternative to conventional testing equipment. These chips integrate multiple functions within a single system, providing a compact and efficient solution for various testing needs. For biochips, a pattern-control micro-electrode-dot-array (MEDA) is a new, universally viable design that can replace microchannels and other micro-components. In a Micro Electrode Dot Array (MEDA), each electrode can be programmatically controlled or dynamically grouped, allowing a single chip to fulfill the diverse requirements of different tests. This capability not only enhances flexibility, but also contributes to cost reduction by eliminating the need for multiple specialized chips. In this paper, we present a visible biochip testing system for tracking the entire testing process in real time, and describe our application of the system to detect SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Simple Summary: Malignant melanoma spreads to other organs and is resistant in part due to the presence of cancer stem cell subpopulations (CSCs). To combat these aggressive subpopulations, different therapies are being studied. Our study aimed to evaluate the anti-tumor effect of interferon-alpha (IFN-α) treatments on melanoma CSCs and explore potential biomarkers. We found that even low doses of IFN-α reduced CSC formation and stemness properties, and led to a significant decrease in the ability to form tumors in mice xenotransplants. IFN-α also modulated the expression of genes and microRNAs involved in several cancer processes and the metabolomics of released exosomes. Our data suggest further investigations of new dose and combination approaches with IFN-α in malignant melanoma. Malignant melanoma (MM) can spread to other organs and is resistant in part due to the presence of cancer stem cell subpopulations (CSCs). While a controversial high dose of interferon-alpha (IFN-α) has been used to treat non-metastatic high-risk melanoma, it comes with undesirable side effects. In this study, we evaluated the effect of low and high doses of IFN-α on CSCs by analyzing ALDH activity, side population and specific surface markers in established and patient-derived primary cell lines. We also assessed the clonogenicity, migration and tumor initiation capacities of IFN-α treated CSCs. Additionally, we investigated genomic modulations related to stemness properties using microRNA sequencing and microarrays. The effect of IFN-α on CSCs-derived exosomes was also analyzed using NanoSight and liquid chromatography (LC-HRMS)-based metabolomic analysis, among others. Our results showed that even low doses of IFN-α reduced CSC formation and stemness properties, and led to a significant decrease in the ability to form tumors in mice xenotransplants. IFN-α also modulated the expression of genes and microRNAs involved in several cancer processes and metabolomics of released exosomes. Our work suggests the utility of low doses of interferon, combined with the analysis of metabolic biomarkers, as a potential clinical approach against the aggressiveness of CSCs in melanoma. [ABSTRACT FROM AUTHOR]

Electrochemical Immunosensing (EI) combines electrochemical analysis and immunology principles and is characterized by its simplicity, rapid detection, high sensitivity, and specificity. EI has become an important approach in various fields, such as clinical diagnosis, disease prevention and treatment, environmental monitoring, and food safety. However, EI multi-component detection still faces two major bottlenecks: first, the lack of cost-effective and portable detection platforms; second, the difficulty in eliminating batch differences and accurately decoupling signals from multiple analytes. With the gradual maturation of biochip technology, high-throughput analysis and portable detection utilizing the advantages of miniaturized chips, high sensitivity, and low cost have become possible. Meanwhile, Artificial Intelligence (AI) enables accurate decoupling of signals and enhances the sensitivity and specificity of multi-component detection. We believe that by evaluating and analyzing the characteristics, benefits, and linkages of EI, biochip, and AI technologies, we may considerably accelerate the development of EI multi-component detection. Therefore, we propose three specific prospects: first, AI can enhance and optimize the performance of the EI biochips, addressing the issue of multi-component detection for portable platforms. Second, the AI-enhanced EI biochips can be widely applied in home care, medical healthcare, and other areas. Third, the cross-fusion and innovation of EI, biochip, and AI technologies will effectively solve key bottlenecks in biochip detection, promoting interdisciplinary development. However, challenges may arise from AI algorithms that are difficult to explain and limited data access. Nevertheless, we believe that with technological advances and further research, there will be more methods and technologies to overcome these challenges. [ABSTRACT FROM AUTHOR]

Simple Summary: The immune system has been shown to play a critical role in controlling tumor development. Therefore, therapeutic strategies based on targeting tumors from this point of view are becoming increasingly important. One of the approaches offered by nanotechnology and small molecules in this context is the induction of immunogenic cell death (ICD). In this work, a characterization of the antitumor response of paramagnetic iron nanoparticles conjugated with a platinum compound is presented. A highlight of this work is the significant improvement in the antitumor properties of the nanoconjugate comparing it with the platinum compound. Moreover, the conjugation has been shown to have crucial properties for the induction of ICD, such as the activation of cellular endoplasmic reticulum stress. Our results emphasize the relevance of nanotechnology as a fundamental strategy for the development of new approaches with onco-immunotherapy activity. From chemistry design to clinical application, several approaches have been developed to overcome platinum drawbacks in antitumoral therapies. An in-depth understanding of intracellular signaling may hold the key to the relationship of both conventional drugs and nanoparticles. Within these strategies, first, nanotechnology has become an essential tool in oncotherapy, improving biopharmaceutical properties and providing new immunomodulatory profiles to conventional drugs mediated by activation of endoplasmic reticulum (ER) stress. Secondly, functional proteomics techniques based on microarrays have proven to be a successful method for high throughput screening of proteins and profiling of biomolecule mechanisms of action. Here, we conducted a systematic characterization of the antitumor profile of a platinum compound conjugated with iron oxide nanoparticles (IONPs). As a result of the nano-conjugation, cytotoxic and proteomics profiles revealed a significant improvement in the antitumor properties of the starting material, providing selectivity in certain tumor cell lines tested. Moreover, cell death patterns associated with immunogenic cell death (ICD) response have also been identified when ER signaling pathways have been triggered. The evaluation in several tumor cell lines and the analysis by functional proteomics techniques have shown novel perspectives on the design of new cisplatin-derived conjugates, the high value of IONPs as drug delivery systems and ICD as a rewarding approach for targeted oncotherapy and onco-immunotherapies. [ABSTRACT FROM AUTHOR]

With increasing effectiveness of flow-based microfluidic biochips in the field of biochemical experiments and point-of-care diagnosis, design automation demands enormous attention to integrate the flow-layer design and control-layer design instead of considering them in isolation. Some severe design issues like valve reliability, control-channel delay, pressure skew, etc. are obvious and they must be tactfully dealt along with minimization of several cost-driving issues like schedule length, pin count, and control-channel length while ensuring planarity of the flow-layer components as well as control-layer channel routes. Hence, this paper aims to propose a unified flow-control co-design methodology considering various flow-control cost-driving issues while reducing the design cycles to obtain a low-cost and efficient platform. The performance is evaluated over several benchmark bioassays that show the efficacy of the proposed co-design method which reduces the number of required valves by 30%, control-channel length by 48.5%, and number of flow-channel crossings by 72.2% than the existing works, on an average. [ABSTRACT FROM AUTHOR]