Field-effect transistor (FET)-based biosensors allow label-free detection of biomolecules by measuring their intrinsic charges. The detection limit of these sensors is determined by the Debye screening of the charges from counter ions in solutions. Here, we use FETs with a deformed monolayer graphene channel for the detection of nucleic acids. These devices with even millimeter scale channels show an ultra-high sensitivity detection in buffer and human serum sample down to 600 zM and 20 aM, respectively, which are ∼18 and ∼600 nucleic acid molecules. Computational simulations reveal that the nanoscale deformations can form 'electrical hot spots' in the sensing channel which reduce the charge screening at the concave regions. Moreover, the deformed graphene could exhibit a band-gap, allowing an exponential change in the source-drain current from small numbers of charges. Collectively, these phenomena allow for ultrasensitive electronic biomolecular detection in millimeter scale structures.

Hypoxia in tumors contributes to overall tumor progression by assisting in epithelial-to-mesenchymal transition, angiogenesis, and metastasis of cancer. In this study, we have synthesized a hypoxia-responsive, diblock copolymer poly(lactic acid)–azobenzene–poly(ethylene glycol), which self-assembles to form polymersomes in an aqueous medium. The polymersomes did not release any encapsulated contents for 50 min under normoxic conditions. However, under hypoxia, 90% of the encapsulated dye was released in 50 min. The polymersomes encapsulated the combination of anticancer drugs gemcitabine and erlotinib with entrapment efficiency of 40% and 28%, respectively. We used three-dimensional spheroid cultures of pancreatic cancer cells BxPC-3 to demonstrate hypoxia-mediated release of the drugs from the polymersomes. The vesicles were nontoxic. However, a significant decrease in cell viability was observed in hypoxic spheroidal cultures of BxPC-3 cells in the presence of drug encapsulated polymersomes. These polymersomes have potential for future applications in imaging and treatment of hypoxic tumors.

Universal platforms for biomolecular analysis using label‐free sensing modalities can address important diagnostic challenges. Electrical field effect‐sensors are an important class of devices that can enable point‐of‐care sensing by probing the charge in the biological entities. Use of crumpled graphene for this application is especially promising. It is previously reported that the limit of detection (LoD) on electrical field effect‐based sensors using DNA molecules on the crumpled graphene FET (field‐effect transistor) platform. Here, the crumpled graphene FET‐based biosensing of important biomarkers including small molecules and proteins is reported. The performance of devices is systematically evaluated and optimized by studying the effect of the crumpling ratio on electrical double layer (EDL) formation and bandgap opening on the graphene. It is also shown that a small and electroneutral molecule dopamine can be captured by an aptamer and its conformation change induced electrical signal changes. Three kinds of proteins were captured with specific antibodies including interleukin‐6 (IL‐6) and two viral proteins. All tested biomarkers are detectable with the highest sensitivity reported on the electrical platform. Significantly, two COVID‐19 related proteins, nucleocapsid (N‐) and spike (S‐) proteins antigens are successfully detected with extremely low LoDs. This electrical antigen tests can contribute to the challenge of rapid, point‐of‐care diagnostics.

Solid tumors are often poorly irrigated due to structurally compromised microcirculation. Uncontrolled multiplication of cancer cells, insufficient blood flow, and the lack of enough oxygen and nutrients lead to the development of hypoxic regions in the tumor tissues. As the partial pressure of oxygen drops below the necessary level (10 psi), the cancer cells modulate their genetic makeup to survive. Hypoxia triggers tumor progression by enhancing angiogenesis, cancer stem cell production, remodeling of the extracellular matrix, and epigenetic changes in the cancer cells. However, the hypoxic regions are usually located deep in the tumors and are usually inaccessible to the intravenously injected drug carrier or the drug. Considering the designs of the reported nanoparticles, it is likely that the drug is delivered to the peripheral tumor tissues, close to the blood vessels. In this study, we prepared lipid nanoparticles (LNs) comprising the synthesized hypoxia-responsive lipid and a peptide–lipid conjugate. We observed that the resultant LNs penetrated to the hypoxic regions of the tumors. Under low oxygen partial pressure, the hypoxia-responsive lipid undergoes reduction, destabilizing the lipid membrane, and releasing encapsulated drugs from the nanoparticles. We demonstrated the results employing spheroidal cultures of the pancreatic cancer cells BxPC-3. We observed that the peptide-decorated, drug encapsulated LNs reduced the viability of pancreatic cancer cells of the spheroids to 35% under hypoxic conditions.

Enzymatic DNA amplification-based approaches involving intercalating DNA-binding fluorescent dyes and expensive optical detectors are the gold standard for nucleic acid detection. As components of a simplified and miniaturized system, conventional silicon-based Ion sensitive field effect transistors (ISFETs) that measure decrease in pH due to generation of pyrophosphates during DNA amplification have been previously reported. In this paper, we use Bst polymerase in a Loop Mediated Isothermal Amplification (LAMP) reaction combined with target specific primers and crumpled graphene field effect transistors (gFET) to electrically detect the amplification by sensing the reduction in primers. Graphene is known to adsorb single stranded DNA due to noncovalent π-π bonds, but not double stranded DNA. Our approach does not require any surface functionalization and allows the detection of primer concentrations at the endpoint of reactions. We chose crumpled gFET over the conventional flat gFET sensors due to their superior sensitivity as recently demonstrated. We were able to detect the endpoint of amplification reaction with starting concentrations down to 8 zeptomolar in 90 minutes including the time of amplification and detection. With its high sensitivity and small footprint, our platform will help bring complex lab based diagnostic and genotyping amplification assays to the point-of-care.