Flexible Sensing Systems for Cancer Diagnostics.

Practical screening tools and ultrasensitive technologies can play pivotal roles in precision cancer profiling for early diagnosis at asymptomatic stages, as well as for monitoring prognosis, risk stratification, and disease recurrence. While a number of sensors and diagnostic tools continue to be developed for ultrasensitive detection and off-site analysis, there has been an increasing interest in point-of-care devices, particularly those that are mechanically flexible and potentially wearable by the patient. In this chapter, we present a critical insight into the integrated engineering approaches involved in such flexible systems. We consider various aspects in the design of flexible devices, the biomarkers of interest, and the different transduction mechanisms by which mechanically flexible devices can be used in the area of cancer monitoring. We then discuss the different types of flexible biosensing platforms that have been developed to date, including wearables on skin and on clothing, and exhaled breath and implantable sensors. Finally, we discuss the design challenges and future outlook in the development of flexible platforms that can provide comprehensive cancer biomarker panels for patients and clinicians.

Substituent Effects Impact Surface Charge and Aggregation of Thiophenol-Labeled Gold Nanoparticles for SERS Biosensors.

SERS immunoassay biosensors hold immense potential for clinical diagnostics due to their high sensitivity and growing interest in multi-marker panels. However, their development has been hindered by difficulties in designing compatible extrinsic Raman labels. Prior studies have largely focused on spectroscopic characteristics in selecting Raman reporter molecules (RRMs) for multiplexing since the presence of well-differentiated spectra is essential for simultaneous detection. However, these candidates often induce aggregation of the gold nanoparticles used as SERS nanotags despite their similarity to other effective RRMs. Thus, an improved understanding of factors affecting the aggregation of RRM-coated gold nanoparticles is needed. Substituent electronic effects on particle stability were investigated using various para-substituted thiophenols. The inductive and resonant effects of functional group modifications were strongly correlated with nanoparticle surface charge and hence their stability. Treatment with thiophenols diminished the negative surface charge of citrate-stabilized gold nanoparticles, but electron-withdrawing substituents limited the magnitude of this diminishment. It is proposed that this phenomenon arises by affecting the interplay of competing sulfur binding modes. This has wide-reaching implications for the design of biosensors using thiol-modified gold surfaces. A proof-of-concept multiplexed SERS biosensor was designed according to these findings using the two thiophenol compounds with the most electron-withdrawing substitutions: NO2 and CN.

Kirigami-Inspired Biodesign for Applications in Healthcare.

Mechanically flexible and conformable materials and integrated devices have found diverse applications in personalized healthcare as diagnostics and therapeutics, tissue engineering and regenerative medicine constructs, surgical tools, secure systems, and assistive technologies. In order to impart optimal mechanical properties to the (bio)materials used in these applications, various strategies have been explored-from composites to structural engineering. In recent years, geometric cuts inspired by the art of paper-cutting, referred to as kirigami, have provided innovative opportunities for conferring precise mechanical properties via material removal. Kirigami-based approaches have been used for device design in areas ranging from soft bioelectronics to energy storage. In this review, the principles of kirigami-inspired engineering specifically for biomedical applications are discussed. Factors pertinent to their design, including cut geometry, materials, and fabrication, and the effect these parameters have on their properties and configurations are covered. Examples of kirigami designs in healthcare are presented, such as, various form factors of sensors (on skin, wearable), implantable devices, therapeutics, surgical procedures, and cellular scaffolds for regenerative medicine. Finally, the challenges and future scope for the successful translation of these biodesign concepts to broader deployment are discussed.

AIE materials for cancer cell detection, bioimaging and theranostics.

AIE materials exhibit weakly emissive or non-emissive properties in dilute solutions while emit powerful fluorescence in the aggregated/solid state. Recently, AIE based materials have gained immense attention due to their multifunctional role in cancer cell detection, bioimaging and cancer theranostics. In this present book chapter, we will highlight recent advancements of AIE materials for different cancer theranostics applications.

Detachable microfluidic device implemented with electrochemical aptasensor (DeMEA) for sequential analysis of cancerous exosomes.

The quantification of cancer-derived exosomes has a strong potential for minimally invasive diagnosis of cancer during its initial stage. As cancerous exosomes form a small fraction of all the exosomes present in blood, ultra-sensitive detection is a prerequisite for the development of exosome-based cancer diagnostics. Herein, a detachable microfluidic device implemented with an electrochemical aptasensor (DeMEA) is introduced for highly sensitive and in-situ quantification of cancerous exosomes. To fabricate the aptasensor, a nanocomposite was applied on the electrode surface followed by electroplating of gold nanostructures. Subsequently, an aptamer against an epithelial cell adhesion molecule is immobilized on the electrode surface to specifically detect cancer-specific exosomes. A microfluidic vortexer is then constructed and implemented in the sensing system to increase the collision between the exosomes and sensing surface using hydrodynamically generated transverse flow. The microfluidic vortexer was integrated with the aptasensor via a 3D printed magnetic housing. The detachable clamping of the two different devices provides an opportunity to subsequently harvest the exosomes for downstream analysis. The DeMEA has high sensitivity and specificity with an ultra-low limit of detection of 17 exosomes/µL over a wide dynamic range (1 × 102 to 1 × 109) exosomes/µL in a short period. As proof of the concept, the aptasensor can be separated from the 3D printed housing to harvest and analyze the exosomes by real-time polymerase chain reaction. Moreover, the DeMEA quantifies the exosomes from plasma samples of patients with breast cancer at different stages of the disease. The DeMEA provides a bright horizon for the application of microfluidic integrated biosensors for the early detection of cancerous biomarkers.

Silk fibroin as a platform for dual sensing of vitamin B12 using photoluminescence and electrical techniques.

The amalgamation of natural origin materials and technologies for label-free and real time detection is pertinent in analytical field. In this study, Bombyx mori silk fibroin protein (BMSF) has been utilized for the dual sensing of vitamin B12 via fluorescence and electrical impedance techniques. The processing of BMSF is done to generate an aqueous solution of BMSF along with the development of micro patterned thin films via soft lithography technique. The BMSF aqueous solution exhibit auto fluorescence property and thereby utilized for label free detection of vitamin B12 with an estimated limit of detection (LOD) of about 0.003 × 10-6 g/uL. This is followed by impedimetric detection of vitamin B12 using the micro patterned BMSF thin films. A LOD of 17.8 ppm and 0.25 ppm are achieved in aqueous solution and human blood serum, respectively. Taken together, this work demonstrates a potential label free dual sensing mode for sensitive detection of micronutrient vitamin B12.

Mobile diagnostics: next-generation technologies for in vitro diagnostics.

The emergence of a wide range of applications of smartphones along with advances in 'liquid biopsy' has significantly propelled medical research particularly in the field of in vitro diagnostics (IVD). Herein, we have presented a detailed analysis of IVD, its associated critical concerns and probable solutions. It also demonstrates the transition in terms of analytes from minimally invasive (blood) to non-invasive (urine, saliva and sweat) and depicts how the different features of a smartphone can be integrated for specific diagnostic purposes. This review basically highlights recent advances in the applications of smartphone-based biosensors in IVD taking into account the following factors: accuracy and portability; quantitative and qualitative analysis; and centralization and decentralization tests. Furthermore, the critical concerns and future direction of diagnostics based on smartphones are also discussed.

A supramolecular nanobiological hybrid as a PET sensor for bacterial DNA isolated from Streptomyces sanglieri.

The development of a rapid, label free, cost effective and highly efficient sensor for DNA detection is of great importance in disease diagnosis. Herein, we have reported a new hybrid fluorescent probe based on a cationic curcumin-tryptophan complex and water soluble mercapto succinic acid (MSA) capped CdTe quantum dots (QDs) for the detection of double stranded DNA (ds DNA) molecules. The cationic curcumin-tryptophan complex (CT) directly interacts with negatively charged MSA capped quantum dots via electrostatic coordination, resulting in photoluminescence (PL) quenching of QDs via the Photoinduced Electron Transfer (PET) process. Further, addition of ds DNA results in restoration of PL, as CT would intercalate between DNA strands. Thus, this process can be utilized for selective sensing of ds DNA via fluorescence measurements. Under optimized experimental conditions, the PL quenching efficiency of QDs is found to be 99.4% in the presence of 0.31 × 10(-9) M CT. Interestingly, the regain in PL intensity of QD-CT is found to be 99.28% in the presence of 1 × 10(-8) M ds DNA. The detection limit for ds DNA with the developed sensing probe is 1.4 × 10(-10) M. Furthermore, the probe is found to be highly sensitive towards bacterial DNA isolated from Streptomyces sanglieri with a detection limit of 1.7 × 10(-6) M. The present work will provide a new insight into preparation of bio-inspired hybrid materials as efficient sensors for disease diagnosis and agricultural development.