Development of Non-Invasive Biosensors for Neonatal Jaundice Detection: A Review.

One of the most common problems many babies encounter is neonatal jaundice. The symptoms are yellowing of the skin or eyes because of bilirubin (from above 2.0 to 2.5 mg/dL in the blood). If left untreated, it can lead to serious neurological complications. Traditionally, jaundice detection has relied on invasive blood tests, but developing non-invasive biosensors has provided an alternative approach. This systematic review aims to assess the advancement of these biosensors. This review discusses the many known invasive and non-invasive diagnostic modalities for detecting neonatal jaundice and their limitations. It also notes that the recent research and development on non-invasive biosensors for neonatal jaundice diagnosis is still in its early stages, with the majority of investigations being in vitro or at the pre-clinical level. Non-invasive biosensors could revolutionize neonatal jaundice detection; however, a number of issues still need to be solved before this can happen. These consist of in-depth validation studies, affordable and user-friendly gadgets, and regulatory authority approval. To create biosensors that meet regulatory requirements, additional research is required to make them more precise and affordable.

A review on the surface modification of materials for 3D-printed diagnostic devices.

Three-dimensional (3D) printing in tissue engineering and biosensing of analytes by using biocompatible materials or modifying surface structures is an upcoming area of study. This review discusses three common surface modification techniques, viz. alkaline hydrolysis, UV light photografting, and plasma treatment. Alkaline hydrolysis involves the reaction of an alkaline solution with the surface of a material, causing the surface to develop carboxyl and hydroxyl groups. This technique can enhance the biocompatibility, surface wettability, adhesion, printability, and dyeability of materials, such as acrylonitrile butadiene styrene (ABS), polycarbonate, and polylactic acid (PLA). This review also mentions details about some of the surface-modified 3D-printed diagnostic devices. Although most of the devices are modified using chemical processes, there are always multiple techniques involved while designing a diagnostic device. We have, therefore, mentioned some of the devices based on the materials used instead of categorising them as per modification techniques. 3D printing helps in the design of sophisticated shapes and structures using multiple materials. They can, therefore be used even in the design of microfluidic devices that are very useful for biosensing. We have also mentioned a few materials for printing microfluidic devices.

Fluorescent fiber-optic device sensor based on carbon quantum dot (CQD) thin films for dye detection in water resources.

Industrialization, especially in textile industries, has led to increased use of dyes and pigments to impart colours to fabrics. Textile dyes are one of the chief emerging pollutants of water resources as industrial effluents. In the current research, we report the development and utilization of pH-sensitive carbon quantum dots (CQDs) immobilized in polymer thin films acting as sensors for textile dye detection. The CQDs and CQD-containing polymer films were characterized by various techniques like XRD, TEM, XPS, and CLSM. The synthesized CQD thin films possess a unique pH-sensitive property that can be used to detect various model acidic and basic dyes that are important components of industrial effluents from textile dyes. The detection capability of the sensor films was evaluated by spiking dyes in various water matrices, like household tap water and river water. The results indicate that pH-sensitive CQD thin film was able to detect three acidic dyes, namely methyl red, methyl orange, and bromocresol green, and one basic dye, methylene blue, in a linear range of 0-100 µM with a response time of 1 minute. The CQD thin-film sensors have a limit of detection of 26.4 ppb, 214.5 ppb, 46.2 ppb, and 29.7 ppb for methyl red, methyl orange, bromocresol green and methylene blue, respectively. The accuracy of detection performed by spiking studies in water resources indicated an ∼100% recovery value in all tested acidic and basic dyes. The sensor films were compared for analytical parameters using UV-visible-fluorescence spectroscopy and HPLC.

Evaluation of phthalic acid tri-ethylene diamine (TED) and folic acid-based carbon quantum dots for the detection of heavy metals in water resources using fibre-optic instrumentation.

Heavy metal pollution and toxicity from water resources have remained a great concern for the entire population. This research demonstrates the capability of carbon quantum dots (CQDs) for fluorescence-based heavy metal detection in different water resources using a fibre-optic spectrometer device. Two different types of CQDs phthalic acid and triethylenediamine (PT CQDs) and Folic acid (FCQDs) were synthesized using microwave irradiation and hydrothermal method, respectively. CQDs were characterized using several techniques such as TEM, EDX, XPS and FTIR. PTCQD and FCQDs both were tested for sensing capability in water reservoirs like household and river water. The results indicate that both CQDs were able to detect all six heavy metal ions (Pb2+, Co2+, Mn3+, Hg2+, Ni2+, Cr3+) tested in the study in the range of 0-100 µM. It was found that FCQDs show a three-fold higher sensitivity and greater resolution than PTCQDs for all the heavy metals samples. The CQDs' sensing capability shows that they can achieve a limit of detection in the range of 0.15-3 µM along with 100% accuracy in terms of recovery with minimal error, these results indicate that both CQDs have a tremendous potential to be used as a sensor for the detection of heavy metals even in complex water matrices. FCQDs show more sensitivity for all metals compared to PTCQDs and used in future as a sensing tool for heavy metal detection with better sensitivity and accuracy with less response time.

Biosensors for detection of prostate cancer: a review.

Diagnosis of prostate cancer (PC) has posed a challenge worldwide due to the sophisticated and costly diagnostics tools, which include DRE, TRUS, GSU, PET/CT scan, MRI, and biopsy. These diagnostic techniques are very helpful in the detection of PCs; however, all the techniques have their serious limitations. Biosensors are easier to fabricate and do not require any cutting-edge technology as required for other imaging techniques. In this regard, point-of-care (POC) biosensors are important due to their portability, convenience, low cost, and fast procedure. This review explains the various existing diagnostic tools for the detection of PCs and the limitation of these methods. It also focuses on the recent studies on biosensors technologies as an alternative to the conventional diagnostic techniques for the detection of PCs.

3D Printed Chitosan Composite Scaffold for Chondrocytes Differentiation.

AIMS: Our aim is to develop 3D printed chitosan-gelatin-alginate scaffolds using a costeffective in house designed 3D printer followed by its characterization. To observe chondrocyte differentiation on 3D printed scaffolds as part of scaffold application. BACKGROUND: Cartilage is considered to be a significant tissue in humans. It is present in between the rib cage, the lobe of the ear, nasal septum in the form of hyaline cartilage, in between ribs costal cartilage, intervertebral discs in the form of fibrocartilage, meniscus, larynx, epiglottis and between various joints of bones. To replace or repair damaged tissues due to disorders or trauma, thousands of surgical procedures are performed daily. 3D printing plays a crucial role in the development of controlled porous architectures of scaffolds for cartilage tissue regeneration. Advancement in 3D printing technology like inkjet, micro- extrusion in 3D bioprinting, Laser-assisted 3D Bioprinting (LAB), stereolithography combination with biomaterials plays a crucial role in the quick development of patient-specific articulating cartilage when need in a short period frame. OBJECTIVE: Our objective is to develop different compositions of chitosan-gelatin-alginate composite hydrogel scaffolds with controlled porosity and architectures with the application of 3D printing and observe the growth of cartilage on it. To achieve as proposed, an in-house 3D paste extruder printer was developed, which is capable of printing porous composite chitosan hydrogel scaffolds of desired architecture layer by layer. After the characterization of 3D printed chitosan composite scaffolds, the differentiation of chondrocyte was observed using hMSC. METHODS: In present paper process for the development of chitosan-alginate-gelatin composite hydrogel, 3D printing, morphological characterization, and observation for differentiation of chondrocytes cells on 3D printed chitosan composite hydrogels is presented. The present study is divided into three parts: in first part development of composite chitosan-alginate-gelatin hydrogel with the utilization of in house customized assembled paste extruder based 3D printer, which is capable of printing chitosan composite hydrogels. In the second part, the characterization of 3D printed chitosan composite scaffolds hydrogel is performed for evaluating the morphological, mechanical, and physical properties. The prepared composite scaffolds were characterized by Fourier Transform Infrared Spectroscopy (FTIR), X-Ray Diffraction(XRD), Scanning Electron Microscopy SEM, swelling property, mechanical testing, porosity, etc. In the last part of the study, the differentiation of chondrocytes cells was observed with human Mesenchymal Stem Cells (hMSC) on 3D printed scaffolds and showed positive results for the same. RESULTS: Stereolithography (STL) files of 3D models for porous chitosan composite were developed using Computer-Aided Design (CAD) and printed with a hydrogel flow rate within the range of 0.2-0.25 ml/min. The prepared scaffolds are highly porous, having optimum porosity, optimal mechanical strength to sustain the cartilage formation. The 3D printed chitosan composite scaffolds show supports for the differentiation of chondrocytes. The above study is helpful for in-vivo regeneration of cartilage for patients having related cartilage disorders. CONCLUSION: This method helps in regeneration of degenerated cartilage for patient-specific and form above experiment we also concluded that 3D printed chitosan scaffold is best suited for the regeneration of chondrocyte cells.

Biocompatibility and therapeutic evaluation of magnetic liposomes designed for self-controlled cancer hyperthermia and chemotherapy.

Magnetic liposome-mediated combined chemotherapy and hyperthermia is gaining importance as an effective therapeutic modality for cancer. However, control and maintenance of optimum hyperthermia are major challenges in clinical settings due to the overheating of tissues. To overcome this problem, we developed a novel magnetic liposomes formulation co-entrapping a dextran coated biphasic suspension of La0.75Sr0.25MnO3 (LSMO) and iron oxide (Fe3O4) nanoparticles for self-controlled hyperthermia and chemotherapy. However, the general apprehension about biocompatibility and safety of the newly developed formulation needs to be addressed. In this work, in vitro and in vivo biocompatibility and therapeutic evaluation studies of the novel magnetic liposomes are reported. Biocompatibility study of the magnetic liposomes formulation was carried out to evaluate the signs of preliminary systemic toxicity, if any, following intravenous administration of the magnetic liposomes in Swiss mice. Therapeutic efficacy of the magnetic liposomes formulation was evaluated in the fibrosarcoma tumour bearing mouse model. Fibrosarcoma tumour-bearing mice were subjected to hyperthermia following intratumoral injection of single or double doses of the magnetic liposomes with or without chemotherapeutic drug paclitaxel. Hyperthermia (three spurts, each at 3 days interval) with drug loaded magnetic liposomes following single dose administration reduced the growth of tumours by 2.5 fold (mean tumour volume 2356 ± 550 mm3) whereas the double dose treatment reduced the tumour growth by 3.6 fold (mean tumour volume 1045 ± 440 mm3) compared to their corresponding control (mean tumour volume 3782 ± 515 mm3). At the end of the tumour efficacy studies, the presence of MNPs was studied in the remnant tumour tissues and vital organs of the mice. No significant leaching or drainage of the magnetic liposomes during the study was observed from the tumour site to the other vital organs of the body, suggesting again the potential of the novel magnetic liposomes formulation for possibility of developing as an effective modality for treatment of drug resistant or physiologically vulnerable cancer.

Biphasic magnetic nanoparticles-nanovesicle hybrids for chemotherapy and self-controlled hyperthermia.

AIM: The aim was to develop magnetic nanovesicles for chemotherapy and self-controlled hyperthermia that prevent overheating of tissues. MATERIALS & METHODS: Magnetic nanovesicles containing paclitaxel and a dextran-coated biphasic suspension of La0.75Sr0.25MnO3 and Fe3O4 nanoparticles (magnetic nanoparticles) were developed. RESULTS: Encapsulation efficiencies of magnetic nanoparticles and paclitaxel were 67 ± 5 and 83 ± 3%, respectively. Sequential release performed at 37°C for 1 h followed by 44°C for another 1 h (as expected for intratumoral injection), showed a cumulative release of 6.6% (109.6 µg), which was above the IC50 of the drug. In an alternating current magnetic field, the temperature remained controlled at 44°C and a synergistic cytotoxicity of paclitaxel and hyperthermia was observed in MCF-7 cells. CONCLUSION: Magnetic nanovesicles containing biphasic suspensions La0.75Sr0.25MnO3 and Fe3O4 nanoparticles encapsulating paclitaxel have potential for combined self-controlled hyperthermia and chemotherapy.

Biocompatibility, biodistribution and efficacy of magnetic nanohydrogels in inhibiting growth of tumors in experimental mice models.

We report in vivo evaluation of a thermo-responsive poly(N-isopropylacrylamide)-chitosan based magnetic nanohydrogel (MNHG) incorporated with Fe3O4 nanoparticles (NPs) in mice models with expandible scope for use in localized delivery of chemotherapeutics. Biocompatibility and biodistribution of the MNHG are studied in normal Swiss mice while efficacy in tumor growth inhibition is studied in a subcutaneous fibrosarcoma tumor. The ex vivo time-dependent pattern of accumulated MNHG into vital organs; lung, liver, spleen, kidney and brain collected at 1 h, 48 h, 7 d and 14 d post intravenous administration are investigated using both a vibrating sample magnetometer (VSM) and inductively coupled plasma-atomic emission spectroscopy (ICP-AES) method. The doses of MNHG (dose I ∼ 650 and dose II ∼ 325 µg g-1 body wt) used in the study are determined based on induced thermal activation of MNHG under an AC magnetic field (AMF). Fibrosarcoma tumor bearing mice are subjected to hyperthermia with a field of 325 Oe and 265 kHz for 30 min following intratumoral administration of dose I. Tumor size measured at an interval of 72 h for a period of 2 weeks reveals that the NPs mediated therapy decelerated the growth of the transplanted tumor by about three-fold (size, 1545 ± 720 mm3) as compared to the exponential growth of the tumor (size, 4510 ± 735 mm3) in control mice. These results suggest the feasibility of using poly(NIPAAm)-chitosan hydrogels loaded with NPs for combined thermo-chemotherapy where the efficacy may further be improved by temperature dependent release of the drugs from the magneto hydrogels.

In vitro application of paclitaxel loaded magnetoliposomes for combined chemotherapy and hyperthermia.

Paclitaxel loaded thermosensitive magnetoliposomes containing 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-rac-glycerol (PG) were prepared by thin film hydration method. Encapsulation efficiencies of paclitaxel and citric acid coated Fe(3)O(4) nanoparticles were 83±3% and 74.6±5%, respectively. Based on the release study, DPPC/PG in 9:1 (w/w) liposomes (PCPG) formulation was found to be thermosensitive and showed 46 fold higher drug release at 43 °C than at 37 °C. Drug release was done under an alternating magnetic field of intensity 10 kA/m and a fixed frequency of 423 kHz. In-vitro cytotoxicity and hyperthermia studies were carried out using a human cervical cancer cell line (HeLa). IC(50) value of the magnetoliposomes formulation was 100 nM. When the magnetoliposomes with 100 nM drug was used to treat HeLa cells in combination with hyperthermia under AC magnetic field, 89% cells were killed and were found to be more effective than either hyperthermia or chemotherapy alone. So, PCPG liposomes which co-encapsulate both Fe(3)O(4) nanoparticles and paclitaxel may be useful for combined chemotherapy and hyperthermia.