ABSTRACT
Pacemaking dysfunction has become a significant disease that may contribute to heart rhythm disorders, syncope, and even death. Up to now, the best way to treat it is to implant electronic pacemakers. However, these have many disadvantages such as limited battery life, infection, and fixed pacing rate. There is an urgent need for a biological pacemaker (bio-pacemaker). This is expected to replace electronic devices because of its low risk of complications and the ability to respond to emotion. Here we survey the contemporary development of the bio-pacemaker by both experimental and computational approaches. The former mainly includes gene therapy and cell therapy, whilst the latter involves the use of multi-scale computer models of the heart, ranging from the single cell to the tissue slice. Up to now, a bio-pacemaker has been successfully applied in big mammals, but it still has a long way from clinical uses for the treatment of human heart diseases. It is hoped that the use of the computational model of a bio-pacemaker may accelerate this process. Finally, we propose potential research directions for generating a bio-pacemaker based on cardiac computational modeling.
ABSTRACT
In this work, a novel conjugate of ractopamine and bovine serum albumin (RAC–BSA) has been developed via the Mannich reaction, with a mole coupling ratio for RAC–BSA of 9:1. The proposed conjugation method provides a simple and one-step method with the use of fewer reagents compared with other conjugation methods for competitive immunoassays. RAC–BSA conjugation was used to fabricate a competitive lateral flow strip test for RAC detection in animal feed. For sample preparation, RAC was spiked in swine feed purchased from the local markets in Thailand, and methanol and running buffer at a volume ratio of 10:90 was used as extraction buffer. The procedures for sample preparation were completed within 25 min. Under optimal conditions, the limit of detection (LOD), assessed by the naked eye within 5 min, was found to be 1 ng/g. A semi-quantitative analysis was also conducted using a smart phone and computer software, with a linearity of 0.075–0.750 ng/g, calculated LOD of 0.10 ng/g, calculated limit of quantitation of 0.33 ng/g, and good correlation of 0.992. The recoveries were found in the range of 96.4%–103.7% with a relative standard deviation of 2.5%–3.6% for intra- and inter-assays. Comparison of the results obtained by the strip test with those obtained by enzyme-linked immunosorbent assay had a good agreement in terms of accuracy. Furthermore, this strip test exhibited highly specific RAC detection without cross reactivity with related compounds. Therefore, the RAC–BSA conjugation via the Mannich reaction can be accepted as a one-step and easy conjugation method and applied to the competitive lateral flow strip test.