Smartphone-Integrated Automated Sensor Employing Electrochemically Engineered 3D Bimetallic Nanoflowers for Hydrogen Peroxide Quantification in Milk.

Hydrogen peroxide (H2O2), one of the reactive oxygen species in living beings, serves as a regulator of various cellular processes. However, excessive peroxide concentrations are linked to oxidative stress and promptly disrupt cellular components, leading to several pathological conditions in the body. Moreover, it is extremely reactive and has a limited lifetime; thus, H2O2 sensing remains a prominent focus of research. Enzymatic sensing probes were widely employed to detect H2O2 in the recent past; however, they are susceptible to intrinsic chemical and thermal instabilities, which decrease the reliability and durability of the surface. This research was designed to come up with a feasible solution to this problem. Herein, a novel nonenzymatic peroxidase-mimic three-dimensional (3D) bimetallic nanoflower has been synergistically engineered for quick sensing of H2O2. The sensor platform showed minimal resistance or enhanced charge transfer properties as well as remarkable analytical capability, having a broad linear range between 0.01 and 1 nM and a detection limit of 1.46 ± 0.07 pM. The probe responded to changes in H2O2 concentration in just 2.10 ± 0.02 s, making it a quick sensing platform for H2O2 tracking. This peroxidase-mimic nanozyme probe showed minimal sensitivity to interferants often seen in real-world sample matrices and possessed good recoveries ranging from 92.88 to 99.09% in milk samples. Further, a facile and user-friendly smartphone application (APP) named "HPeroxide-Check" was developed and integrated into the sensor to check the milk adulteration by detecting H2O2. It processes the current output obtained from the sensing interface and provides real-time peroxide concentrations in milk. The entire procedure of fabricating the probe is a single, highly robust step that takes only 10 min and is coupled with a smartphone APP, highlighting the sensor's quick manufacturing and deployment for automated H2O2 monitoring in industrial and point-of-care settings.

Highly electrochemically active Ti3C2Tx MXene/MWCNT nanocomposite for the simultaneous sensing of paracetamol, theophylline, and caffeine in human blood samples.

The facile fabrication is reported of highly electrochemically active Ti3C2Tx MXene/MWCNT (3D/1D)-modified screen-printed carbon electrode (SPE) for the efficient simultaneous electrochemical detection of paracetamol, theophylline, and caffeine in human blood samples. 3D/1D Ti3C2Tx MXene/MWCNT nanocomposite was synthesized using microwave irradiation and ultrasonication processes. Then, the Ti3C2Tx/MWCNT-modified SPE electrode was fabricated and thoroughly characterized towards its physicochemical and electrochemical properties using XPS, TEM, FESEM, XRD, electrochemical impedance spectroscopy, cyclic voltammetry, and differential pulse voltammetry techniques. As-constructed Ti3C2Tx-MWCNT/SPE offers excellent electrochemical sensing performance with good detection limits (0.23, 0.57, and 0.43 µM) and wide linear ranges (1.0 ~ 90.1, 2.0 ~ 62.0, and 2.0-90.9 µM) for paracetamol, caffeine, and theophylline, respectively,  in the human samples. Notably, the non-enzymatic electroactive nanocomposite-modified electrode has depicted a semicircle Nyquist plot with low charge transfer resistance (Rct∼95 Ω), leading to high ionic diffusion and facilitating an excellent electron transfer path. All the above results in efficient stability, reproducibility, repeatability, and sensitivity compared with other reported works, and thus, it claims its practical utilization in realistic clinical applications.

Design and development of opto-electrochemical biosensing devices for diagnosing chronic kidney disease.

Chronic kidney disease (CKD) is emerging as one of the major causes of the increase in mortality rate and is expected to become 5th major cause by 2050. Many studies have shown that it is majorly related to various risk factors, and thus becoming one of the major health issues around the globe. Early detection of renal disease lowers the overall burden of disease by preventing individuals from developing kidney impairment. Therefore, diagnosis and prevention of CKD are becoming the major challenges, and in this situation, biosensors have emerged as one of the best possible solutions. Biosensors are becoming one of the preferred choices for various diseases diagnosis as they provide simpler, cost-effective and precise methods for onsite detection. In this review, we have tried to discuss the globally developed biosensors for the detection of CKD, focusing on their design, pattern, and applicability in real samples. Two major classifications of biosensors based on transduction systems, that is, optical and electrochemical, for kidney disease have been discussed in detail. Also, the major focus is given to clinical biomarkers such as albumin, creatinine, and others related to kidney dysfunction. Furthermore, the globally developed sensors for the detection of CKD are discussed in tabulated form comparing their analytical performance, response time, specificity as well as performance in biological fluids.

Gold nanostar and graphitic carbon nitride nanocomposite for serotonin detection in biological fluids and human embryonic kidney cell microenvironment.

A nanosensor comprising of gold nanostars (Au-Nstars)-graphitic carbon nitride (g-C3N4) nanocomposite layered on a glassy carbon electrode (GCE) to detect serotonin (ST) in various body fluids has been fabricated. The nanocomposite and the sensing platform have been thoroughly characterized with UV-visible spectroscopy (UV-vis), transmission electron microscopy (TEM), selected area electron diffraction (SAED), energy dispersive X-ray photoelectron spectroscopy (EDX), and electrochemical techniques such as cyclic voltammetry (CV), linear sweep voltammetry (LSV), and electrochemical impedance spectroscopy (EIS). The designed ST detection probe has achieved a linear dynamic range (LDR) in the range 5 × 10-7 and 1 × 10-3 M with a limit of detection (LOD) of 15.1 nM (RSD < 3.3%). The ST detection capability of the fabricated sensor ranges between the normal and several abnormal pathophysiological situations. The sensor effectively detects ST in real matrices such as urine and blood serum, thus, showing its direct diagnostic applicability. Additionally, the sensor has been tested in the microenvironment of human embryonic kidney (HEK) cells to assess the possibility of ST secretion in cell lines. Interferences because of co-existing molecules have been evaluated, and the shelf-life of the fabricated sensor has been obtained as 8 weeks.

Nano-bio-engineered silk matrix based devices for molecular bioanalysis.

Silk is a fibrous protein, has been a part of human lives for centuries,  and was used as suture and textile material. Silk is mainly produced by the members of certain arthropods such as spiders, butterflies, mites, and moths. However, recent technological advances have revolutionized silk as a biomaterial for various applications ranging from heat sensors to robust fibers. The biocompatibility, mechanical resilience, and biodegradability of the material make it a suitable candidate for biomaterials. Silk can also be easily converted into several morphological forms, including fibers, films, sponges, and hydrogels. Provided these abilities, silk have received excellent traction from scientists worldwide for various developments, one of them being its use as a bio-sensor. The diversity of silk materials offers various options, giving scientists the freedom to choose from and personalize them as per their needs. In this review, we foremost look upon the composition, production, properties, and various morphologies of silk. The numerous applications of silk and its derivatives for fabricating biosensors to detect small molecules, macromolecules, and cells have been explored comprehensively. Also, the data from various globally developed sensors using silk have been described into organized tables for each category of molecules, along with their important analytical details.

Marine biological macromolecules as matrix material for biosensor fabrication.

The ocean covers two-third of our planet and has great biological heterogeneity. Marine organisms like algae, vertebrates, invertebrates, and microbes are known to provide many natural products with biological activities as well as potential sources of biomaterials for therapeutic, biomedical, biosensors, and climate stabilization. Over the years, the field of biosensors has gained huge attention due to their extraordinary ability to provide early disease diagnosis, rapid detection of various molecules and substances along with long-term monitoring. This review aims to focus on the properties and employment of various biomaterials (carbohydrate polymers, proteins, polyacids, etc.) of marine origins such as alginate, chitin, chitosan, fucoidan, carrageenan, chondroitin sulfate, hyaluronic acid, collagen, marine pigments, marine nanoparticles, hydroxyapatite, biosilica, lectins, and marine whole cell in the design and development of biosensors. Furthermore, this review also covers the source of such marine biomaterials and their promising evolution in the fabrication of biosensors that are potent to be employed in the biomedical, environmental science, and agricultural sciences domains. The use of such fabricated biosensors harnesses the system with excellent specificity, selectivity, biocompatibility, thermal stability, and minimal cost advantages.

Ligand conjugated lipid-based nanocarriers for cancer theranostics.

Cancer is one of the major health-related issues affecting the population worldwide and subsequently accounts for the second-largest death. Genetic and epigenetic modifications in oncogenes or tumor suppressor genes affect the regulatory systems that lead to the initiation and progression of cancer. Conventional methods, including chemotherapy/radiotherapy/appropriate combinational therapy and surgery, are being widely used for theranostics of cancer patients. Surgery is useful in treating localized tumors, but it is ineffective in treating metastatic tumors, which spread to other organs and result in a high recurrence rate and death. Also, the therapeutic application of free drugs is related to substantial issues such as poor absorption, solubility, bioavailability, high degradation rate, short shelf-life, and low therapeutic index. Therefore, these issues can be sorted out using nano lipid-based carriers (NLBCs) as promising drug delivery carriers. Still, at most, they fail to achieve site-targeted drug delivery and detection. This can be achieved by selecting a specific ligand/antibody for its cognate receptor molecule expressed on the surface of the cancer cells. In this review, we have mainly discussed the various types of ligands used to decorate NLBCs. A list of the ligands used to design nanocarriers to target malignant cells has been extensively undertaken. The approved ligand-decorated lipid-based nanomedicines with their clinical status have been explained in tabulated form to provide a wider scope to the readers regarding ligand-coupled NLBCs.

Sputtering enhanced peroxidase like activity of a dendritic nanochip for amperometric determination of hydrogen peroxide in blood samples.

A nonenzymatic electrochemical nanoprobe is described for the fast determination of hydrogen peroxide (H2O2). A sputtered indium tin oxide electrode with a nano-hierarchical 3D gold structure is used. The nanoprobe was characterized by SEM, EDX, TEM, SAED, and electrochemical techniques. Figures of merit include (a) a fast response time (≤ 1.0 s), (b) two linear dynamic ranges that extend from 10-12 M to 10-10 M and from 10-10 M to10-5 M; and (c) a low limit of detection of 9.8 × 10-13 M. The nanoprobe works in the clinical range and was applied for trace analysis of H2O2 in spiked blood samples, and recoveries ranged between 90 and 96%. It has negligible response (p < 0.001, for n = 3) toward glucose, citric acid, ascorbic acid, uric acid, glycine, and alanine. The shelf-lifetime is found to be 12 weeks. Graphical abstract Schematic representation of a dendritic nanochip with peroxidase-like activity. It is made from an indium tin oxide electrode with a nanohierarchical gold structure and was used for amperometric determination of hydrogen peroxide.

Bioengineered cellulosic paper micro-device for serum albumin detection in clinical range.

Chronic Kidney Disease (CKD) is becoming one of the major causes of morbidity and mortalities in 21st century. We have developed a bioengineered cellulosic paper device for the quantification of albumin (ALB) in physiological samples. The paper surface was activated and antibodies specific to target biomarker was immobilized on engineered paper surface. Every step after modification was characterized by FTIR, XPS, SPM and optical analysis. Further, the device model was designed using CAD file, and a 3-D cascade device was fabricated with in-built constant light source to provide proper and controlled environment for in-situ image analysis. After adding the sample on the bioengineered paper, the antigen-antibody reaction takes place, after that addition of dye results in change of color from yellow to blueish-green within 40 s. An optical method was employed for the analysis of the images by recognizing the specific area and the color intensity. Additionally, the immunosensor specificity was evaluated on number of molecules that are usually found in the serum sample. The linear dynamic range of the developed immunosensor has been reported to be 1-60 mg/mL, covering the normal as well as clinical range of ALB in physiological samples with a detection limit of 0.049(±0.002) mg/mL. With good precision and recovery, the device was able to successfully determine the ALB concentrations in serum sample. The developed device has simple and user-friendly interface and it may also help diagnosing CKD in personalized settings.

Shifting paradigm in electrochemical biosensing matrices comprising metal organic frameworks and their composites in disease diagnosis.

Metal Organic Frameworks (MOFs) are an evolving category of crystalline microporous materials that have grabbed the research interest for quite some time due to their admirable physio-chemical properties and easy fabrication methods. Their enormous surface area can be a working ground for innumerable molecular adhesions and site for potential sensor matrices. They have been explored in the last decade for incorporation in electrochemical sensor matrices as diagnostic solutions for a plethora of diseases. This review emphasizes on some of the recent advancements in the area of MOF-based electrochemical biosensors with focus on various important diseases and their significance in upgrading the sensor performance. It summarizes MOF-based biosensors for monitoring biomarkers relevant to diabetes, viral and bacterial sepsis infections, neurological disorders, cardiovascular diseases, and cancer in a wide range of real matrices. The discussion has been supplemented with extensive tables elaborating recent trends in the field of MOF-composite probe fabrication strategies with their respective sensing parameters. The article sums up the future scope of these materials in the field of biosensors and enlightens the reader with recent trends for future research scope. This article is categorized under: Diagnostic Tools > Biosensing Diagnostic Tools > Diagnostic Nanodevices.

Thiazole-Based Silver Ion Sensor for Sequential Colorimetric Visualization of Epinephrine in the Brain Tissues of an Alzheimer's Disease Model of Mouse.

A thiazole-based probe, N'-((2-aminothiazol-5-yl)methylene)benzohydrazide (TBH), has been efficiently synthesized and characterized for the selective and sensitive detection of the neurotransmitter epinephrine (EP). The sensing strategy is based on the use of TBH for sequential colorimetric sensing of Ag+ and EP via in situ formation of Ag nanoparticles (Ag NPs) from the TBH-Ag+ complex. The generated Ag NPs lead to a bathochromic shift in absorption maximum and a change in color of the solution from light brown to reddish brown. TBH-Ag+ shows remarkable selectivity toward EP versus other drugs, common cations, anions, and some biomolecules. Moreover, TBH-Ag+ has a low detection limit for EP at 1.2 nM. The coordination of TBH-Ag+ has been proposed based on Job's plot, Fourier transform infrared spectroscopy (FT-IR), high-resolution mass spectrometry (HRMS), 1H NMR titration, X-ray photoelectron spectroscopy (XPS), energy-dispersive X-ray analysis (EDAX), and density functional theory (DFT) studies. The composition and morphology of the generated Ag NPs have been analyzed by XPS, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and dynamic light scattering (DLS). The proposed sensing mechanism for EP has been supported by XPS of Ag after the reaction. Further, the sensitivity of TBH-Ag+ toward EP in brain tissues of an Alzheimer's disease model of mouse has been evaluated. A thorough comparison was done for evaluation of the proposed method.

A rapid and sensitive analytical methodology for the simultaneous biomonitoring of two direct oral anticoagulant drugs and their major metabolites in thromboembolic disordered patients samples for clinical evaluations.

Apixaban and dabigatran are the two major direct oral anticoagulant drugs to treat thromboembolic disordered patients. Increasing the clinical application for the thromboembolic disorder and monitoring the concentrations of apixaban, dabigatran, and their metabolites are essential in most clinical circumstances. In this work, we developed a rapid analytical methodology comprising of vortex-assisted salt-enhanced liquid-liquid microextraction technique coupled with UHPLC-MS/MS for the extraction and simultaneous determination of two major direct oral anticoagulant drugs (apixaban, dabigatran), and their two major metabolites from plasma, serum, and urine samples of patients. The developed method was optimized with various procedural steps and validated to study the analytical merits. The developed method yielded a good detection limit of 0.01 ∼ 0.37 ng/mL, 0.01 ∼ 0.32 ng/ml, and 0.01 ∼ 0.27 ng/mL for four target analytes in the plasma, serum, and urine matrices. Moreover, extraction recoveries ranged from 85.11 - 113.57% (for plasma), 89.63 - 110.47% (for serum), and 87.44 -106.79% (for urine samples) with 8.78% RSD. In addition, the method exhibited good R2 values of 0.999 for all four target analytes, and the specificity and carryover study revealed no carryover effect from the UHPLC-MS/MS system for determining the apixaban, dabigatran, and their metabolites. Due to the above advantages, the developed analytical technique was applied to examine 11 real-time clinical patients' samples, and the observed results were satisfactory for all three different sample matrices. Therefore, this analytical method can be applied for biomonitoring apixaban, dabigatran, and their two major metabolites with high sensitivity in a short time for various clinical applications.

Innovative technologies for the fabrication of 3D/4D smart hydrogels and its biomedical applications - A comprehensive review.

Repairing and regenerating damaged tissues or organs, and restoring their functioning has been the ultimate aim of medical innovations. 'Reviving healthcare' blends tissue engineering with alternative techniques such as hydrogels, which have emerged as vital tools in modern medicine. Additive manufacturing (AM) is a practical manufacturing revolution that uses building strategies like molding as a viable solution for precise hydrogel manufacturing. Recent advances in this technology have led to the successful manufacturing of hydrogels with enhanced reproducibility, accuracy, precision, and ease of fabrication. Hydrogels continue to metamorphose as the vital compatible bio-ink matrix for AM. AM hydrogels have paved the way for complex 3D/4D hydrogels that can be loaded with drugs or cells. Bio-mimicking 3D cell cultures designed via hydrogel-based AM is a groundbreaking in-vivo assessment tool in biomedical trials. This brief review focuses on preparations and applications of additively manufactured hydrogels in the biomedical spectrum, such as targeted drug delivery, 3D-cell culture, numerous regenerative strategies, biosensing, bioprinting, and cancer therapies. Prevalent AM techniques like extrusion, inkjet, digital light processing, and stereo-lithography have been explored with their setup and methodology to yield functional hydrogels. The perspectives, limitations, and the possible prospects of AM hydrogels have been critically examined in this study.

Stimuli Responsive Molecular Exchange of Structure Directing Agents on Gold Nanobipyramids: Cancer Cell Detection and Synergistic Therapeutics.

Surface-engineered gold nanoparticles have been considered as versatile systems for theranostics applications. Moreover, surface covering or stabilizing agents on gold nanoparticles especially gold nanobipyramids (AuNBPs) provides an extra space for cargo molecules entrapment. However, it is not well studied yet and also the preparation of AuNBPs still remains dependent largely on cetyltrimethylammonium bromide (CTAB), a cytotoxic surfactant. Therefore, the direct use of CTAB stabilized nanoparticles is not recommended for cancer theranostics applications. Herein, we address an approach of dodecyl ethyl dimethylammonium bromide (DMAB) as biocompatible structure directing agent for AuNBPs, which also accommodate anticancer drug doxorubicin (45%), an additional chemotherapeutics agent. Upon near-infrared light (NIR, 808 nm) exposure, engineered AuNBPs exhibit (i) better phototransduction (51 °C) due to NIR absorption ability (650-900 nm), (ii) photo triggered drug release (more than 80%), and (iii) synergistic chemophototherapy for breast cancer cells. Drug release response has been evaluated in tumor microenvironment conditions (84% in acidic pH and 80% at high GSH) due to protonation and high affinity of thiol binding with AuNBPs followed by DMAB replacement. Intracellular glutathione (GSH, 5-7.5 mM) replaces DMAB from AuNBPs, which cause easy aggregation of nanoparticles as corroborated by colorimetric shifts, suggesting their utilization as a molecular sensing probe of early stage cancer biomarkers. Our optimized recipe yield is monodisperse DMAB-AuNBPs with ∼90% purity even at large scales (500 mL volume per batch). DMAB-AuNBPs show better cell viability (more than 90%) across all concentrations (5-500 ug/mL) when directly compared to CTAB-AuNBPs (less than 10%). Our findings show the potential of DMAB-AuNBPs for early stage cancer detection and theranostics applications.

Ultrasensitive and selective electrochemical diagnosis of breast cancer based on a hydrazine-Au nanoparticle-aptamer bioconjugate.

Human epidermal growth factor receptor 2 (HER2) and HER2-overexpressing breast cancer cells were detected using an electrochemical immunosensor combined with hydrazine and aptamer-conjugated gold nanoparticles (AuNPs). The sensor probe was fabricated by covalently immobilizing anti-HER2 onto a nanocomposite layer that was composed of self-assembled 2,5-bis(2-thienyl)-1H-pyrrole-1-(p-benzoic acid) (DPB) on AuNPs. The hydrazine-AuNP-aptamer bioconjugate, where the hydrazine reductant was directly attached onto AuNPs to avoid the nonspecific deposition of silver on the sensor surface, was designed and used to reduce silver ion for signal amplification selectively. The silver-stained target cells were visualized easily by the bare eye and an optical microscope, and the cells were quantitatively analyzed using stripping voltammetry. The parameters affecting the analytical response were optimized. The proposed sensor was capable of differentiating between HER2-positive breast cancer cells and HER2-negative cells. This method exhibited an excellent diagnosis method for the ultrasensitive detection of SK-BR-3 breast cancer cells in human serum samples with a detection limit of 26 cells/mL.

Personalized biosensors for point-of-care diagnostics: from bench to bedside applications.

The most significant feature of translational point-of-care technology "Personalized biosensors" is that it can be done quickly and by clinical staff who are not trained in clinical laboratory sciences. Rapid test results can quickly give a doctor or other medical worker answers that can help them decide what to do or how to treat a patient. This is helpful almost everywhere, from the emergency room to a patient getting care at home. When a doctor meets a patient for the first time, during a flare-up of a known problem or when a new symptom shows up in a patient who is already being treated, having faster access to test results gives the doctor answers when they are with the patient or are about to see the patient which indicate the importance of point-of-care technologies and their future scope.

Development of a palm-sized bioelectronic sensing device for protein detection in milk samples.

The present study relates a portable optical sensing device supported by a small single-board (SBC) computer. The electronic architectural avenue connects the SBC with a camera, LED lights and a monitor. A 'sensor integration unit' has been linked with the device where the biological reactions were performed and assessed based on the concentration-dependent optical signal outputs. This setup can detect the generation of colors and distinguish their changes in the RGB intensity scale with an accuracy of a single pixel unit. A predefined range of values was obtained and fed to the device that can quantitatively sense the molecule of interest on the sensing matrix. The device has a touchscreen interactive panel that allows users to manually set experimental conditions and connect the entire measurement process to the cloud storage for backup information. We have considered detecting Alkaline Phosphatase (ALP) quantitatively from standard solutions as well as in milk samples as a proof-of-concept protein molecule. The device has shown exceptional analytical performance for lower and higher concentration ranges (0-100 U/mL and 100-1000 U/mL) with correlation coefficient values of 0.99. The detection limit of ALP was determined to be 0.1 U/mL, and the average time of a sample assessment was recorded to be 15 s. The device has also been tested against ALP-spiked milk samples to check its effectiveness and commercial viability. The outcome of the real-time assessment was sensitive and efficient, indicating its direct commercial and clinical importance towards colorimetric detection for diverse macromolecules.

Electrochemical Nano-Imprinting of Trimetallic Dendritic Surface for Ultrasensitive Detection of Cephalexin in Pharmaceutical Formulations.

Cephalexin (CFX), a first-generation cephalosporin, is used to treat various infectious diseases. Although antibiotics have achieved considerable progress in the eradication of infectious diseases, their incorrect and excessive usage has contributed to various side effects, such as mouth soreness, pregnancy-related pruritus, and gastrointestinal symptoms, including nausea, epigastric discomfort, vomiting, diarrhoea, and haematuria. In addition to this, it also causes antibiotic resistance, one of the most pressing problems in the medical field. The World Health Organization (WHO) claims that cephalosporins are currently the most commonly used drugs for which bacteria have developed resistance. Hence, it is crucial to detect CFX in complex biological matrices in a highly selective and sensitive way. In view of this, a unique trimetallic dendritic nanostructure comprised of cobalt, copper, and gold was electrochemically imprinted on an electrode surface by optimising the electrodeposition variables. The dendritic sensing probe was thoroughly characterised using X-ray photoelectron spectroscopy, scanning electron microscopy, chronoamperometry, electrochemical impedance spectroscopy, and linear sweep voltammetry. The probe displayed superior analytical performance, with a linear dynamic range between 0.05 nM and 105 nM, limit of detection of 0.04 ± 0.01 nM, and response time of 4.5 ± 0.2 s. The dendritic sensing probe displayed minimal response to interfering compounds, such as glucose, acetaminophen, uric acid, aspirin, ascorbic acid, chloramphenicol, and glutamine, which usually occur together in real matrices. In order to check the feasibility of the surface, analysis of a real sample was carried out using the spike and recovery approach in pharmaceutical formulations and milk samples, yielding current recoveries of 93.29-99.77% and 92.66-98.29%, respectively, with RSD < 3.5%. It only took around 30 min to imprint the surface and analyse the CFX molecule, making it a quick and efficient platform for drug analysis in clinical settings.

Bioengineering of bone tissues using bioreactors for modulation of mechano-sensitivity in bone.

Since the last decade, significant developments have been made in the area of bone tissue engineering associated with the emergence of novel biomaterials as well as techniques of scaffold fabrication. Despite all these developments, the translation from research findings to clinical applications is still very limited. Manufacturing the designed tissue constructs in a scalable manner remains the most challenging aspect. This bottleneck could be overcome by using bioreactors for the manufacture of these tissue constructs. In this review, a current scenario of bone injuries/defects and the cause of the translational gap between laboratory research and clinical use has been emphasized. Furthermore, various bioreactors being used in the area of bone tissue regeneration in recent studies have been highlighted along with their advantages and limitations. A vivid literature survey on the ideal attributes of bioreactors has been accounted, viz. dynamic, versatile, automated, reproducible and commercialization aspects. Additionally, the illustration of computational approaches that should be combined with bone tissue engineering experiments using bioreactors to simulate and optimize cellular growth in bone tissue constructs has also been done extensively.

Printed circuit boards: system automation and alternative matrix for biosensing.

Circuit integration has revolutionized the diagnostic sector by improving the sensing ability and rapidity of biosensors. Bioelectronics has led to the development of point-of-care (PoC) devices, offering superior performance compared with conventional biosensing systems. These devices have lower production costs, are smaller, and have greater reproducibility, enabling the construction of compact sensing modules. Flexible upgrades to the fabrication pattern of the printed circuit board (PCB) remains the most reliable and consistent means so far, offering portability, wearability, a lower detection limit, and smart output integration to these devices. This review summarizes the advances in PCB technology for biosensing devices for introducing automation and their emerging application as an alternative matrix material for detecting various analytes.