Digital Microfluidics with an On-Chip Drug Dispenser for Single or Combinational Drug Screening.

Rapid and accurate cancer drug screening is of great importance in precision medicine. However, the limited amount of tumor biopsy samples has hindered the application of traditional drug screening methods with microwell plates for individual patients. A microfluidic system provides an ideal platform for handling trace amounts of samples. This emerging platform has a good role in nucleic acid-related and cell related assays. Nevertheless, convenient drug dispensing remains a challenge for clinical on-chip cancer drug screening. Similar sized droplets are merged to add drugs for a desired screened concentration which significantly complicated the on-chip drug dispensing protocols. Here, we introduce a novel digital microfluidic system with a specially structured electrode (a drug dispenser) to dispense drugs by droplet electro-ejection under a high-voltage actuation signal, which can be conveniently adjusted by external electric controls. With this system, the screened drug concentrations span up to four orders of magnitude with small sample consumption. Various amounts of drugs can be delivered to the cell sample with desired amount in a flexible electric control. Moreover, single drug or combinatorial multidrug on-chip screening can be readily achieved. The drug response of normal MCF-10A breast cells and MDA-MB-231 breast tumor cells to two chemotherapeutic substances, cisplatin (Cis) and epirubicin (EP), was tested individually and in combination for proof-of-principle verification. The comparable on-chip and off-chip results confirmed the feasibility of our innovative DMF system for cancer drug screening.

Synthesis of selenophene-based chalcone analogs and assessment of their biological activity as anticancer agents.

Selenium is an essential micronutrient that is beneficial to human health. Selenium-containing drugs have been developed as antioxidants, anti-inflammatory, and anticancer agents. However, the synthesis of selenium-containing chalcones has not been fully explored. Therefore, we report the synthesis of novel selenophene-based chalcone analogs and reveal their biological activities as anticancer agents. Among the seven synthesized molecules, compounds 6, 8, and 10 exhibited anticancer activity with IC50 values of 19.98 ± 3.38, 38.23 ± 3.30, and 46.95 ± 5.68 µM, respectively, against human colorectal adenocarcinoma (HT-29) cells. Clonogenic assays and Western blot analysis tests further confirmed that compound 6 effectively induced apoptosis in HT-29 cells through mitochondrial- and caspase-3-dependent pathways.

Comparison of Various Solvent Extracts and Major Bioactive Components from Portulaca oleracea for Antioxidant, Anti-Tyrosinase, and Anti-α-Glucosidase Activities.

Portulaca oleracea is a well-known species for traditional medicine and food homology in Taiwan. In traditional medicine, P. oleracea is also used to treat gastrointestinal disorders, liver inflammation, fever, severe inflammation, and headaches. We investigated antioxidant, anti-tyrosinase, and anti-α-glucosidase activities of various solvent extracts and major bioactive components from P. oleracea. Ethanol and acetone extracts showed potent DPPH, ABTS, and hydroxyl radical scavenging activities. Chloroform and n-hexane extracts displayed significant superoxide radical scavenging activity. Furthermore, ethyl acetate and acetone extracts of P. oleracea showed potent anti-tyrosinase and anti-α-glucosidase activities. Examined and compared to the various solvent extracts for their chemical compositions using HPLC analysis, we isolated seven major compounds and analyzed their antioxidant, anti-tyrosinase, and anti-α-glucosidase activities. Seven active compounds of P. oleracea, especially quercetin, rosmarinic acid, and kaempferol, exhibited obvious antioxidant, anti-tyrosinase, and anti-α-glucosidase activities. The molecular docking model and the hydrophilic interactive mode of tyrosinase and α-glucosidase revealed that active compounds might have a higher antagonistic effect than commonly inhibitors. Our result shows that the active solvent extracts and their components of P. oleracea have the potential as natural antioxidants, tyrosinase and α-glucosidase inhibitors. Our results suggest that the active solvent extracts of P. oleracea and their components have potential as natural antioxidants, tyrosinase and α-glucosidase inhibitors.

Cancer drug screening with an on-chip multi-drug dispenser in digital microfluidics.

Microfluidics has been the most promising platform for drug screening with a limited number of cells. However, convenient on-chip preparation of a wide range of drug concentrations remains a large challenge and has restricted wide acceptance of microfluidics in precision medicine. In this paper, we report a digital microfluidic system with an innovative control structure and chip design for on-chip drug dispensing to generate concentrations that span three to four orders of magnitude, enabling single drug or combinatorial multi-drug screening with simple electronic control. Specifically, we utilize droplet ejection from a drug drop sitting on a special electrode, named a drug dispenser, under high-voltage pulse actuation to deliver the desired amount of drugs to be picked up by a cell suspension drop driven by low-voltage sine wave actuation. Our proof-of-principle validation for this technique as a convenient single and multi-drug screening involved testing of the drug toxicity of two chemotherapeutics, cisplatin (Cis) and epirubicin (EP), towards MDA-MB-231 breast cancer cells and MCF-10A normal breast cells. The results are consistent with those screened based on traditional 96-well plates. These findings demonstrate the reliability of the drug screening system with an on-chip drug dispenser. This system with fewer cancer cells, less drug consumption, a small footprint, and high scalability with regard to concentration could pave the way for drug screening on biopsied primary tumor cells for precision medicine or any concentration-related research.

Evaluation of Antioxidant and Anti-α-glucosidase Activities of Various Solvent Extracts and Major Bioactive Components from the Seeds of Myristica fragrans.

Myristica fragrans is a well-known species for flavoring many food products and for formulation of perfume and medicated balm. It is also used to treat indigestion, stomach ulcers, liver disorders, and, as emmenagogue, diaphoretic, diuretic, nervine, and aphrodisiac. We examined antioxidant properties and bioactive compounds in various solvent extracts from the seeds of M. fragrans. Methanol, ethanol, and acetone extracts exhibited relatively strong antioxidant activities by 2,2-diphenyl-1-(2,4,6-trinitrophenyl)hydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), superoxide radical, and hydroxyl radical scavenging tests. Furthermore, methanol extracts also displayed significant anti-α-glucosidase activity. Examined and compared to the various solvent extracts for their chemical compositions using HPLC analysis, we isolated the ten higher content compounds and analyzed antioxidant and anti-α-glucosidase activities. Among the isolates, dehydrodiisoeugenol, malabaricone B and malabaricone C were main antioxidant components in seeds of M. fragrans. Malabaricone C exhibited stronger antioxidant capacities than others based on lower half inhibitory concentration (IC50) values in DPPH and ABTS radical scavenging assays, and it also showed significant inhibition of α-glucosidase. These results shown that methanol was found to be the most efficient solvent for extracting the active components from the seeds of M. fragrans, and this material is a potential good source of natural antioxidant and α-glucosidase inhibitor.