A Benchtop Robotic Automation Approach for Manufacturing Prefilled Syringes

Automation and robotics have become a staple in the biological manufacturing sector due to their ability to efficiently work without operator inputs, with a high degree of accuracy and repeatability. Industrial robotic arms, in particular, present themselves as valuable tools for biological manufacturing scenarios that require customized solutions due to their ease of programming and flexibility. The traditional hospital-focused healthcare system was organically developed to address acute conditions, however, in recent years, due to the unprecedented occurrence of emergencies happening more frequently, fast and efficient drug production becomes important [17]. This thesis represents the use of a benchtop robot and automation system capable of manufacturing in-syringe liquid drugs. The compacted production space and design is aimed to provide an efficient production rate. The International Organization for Standardization (ISO) compliant robotic arm (St¨aubli TX2-60), customized designed end-effector, syringe venting system, and Cartesian gantry platform were designed, prototyped, and integrated to create an automated solution for manufacturing cyclic olefin copolymer (COC) polymer syringes. A Siemens programmable logic controller (PLC) system is developed to interface with the robot (through the St¨aubli Robotic Suite (SRS)) and the Nema-17 motor-driven Cartesian gantry platform. Automated filling of a tray of 50ml syringes was proven to be feasible, and the process of stoppering a COC syringe utilizing a customized designed venting tube was demonstrated as a proof of concept. An automated gantry system was also demonstrated as a proof of concept for a complete manufacturing system

Unified empirical likelihood ratio tests for functional concurrent linear models and the phase transition from sparse to dense functional data

We consider the problem of testing functional constraints in a class of functional concurrent linear models where both the predictors and the response are functional data measured at discrete time points. We propose test procedures based on the empirical likelihood with bias‐corrected estimating equations to conduct both pointwise and simultaneous inferences. The asymptotic distributions of the test statistics are derived under the null and local alternative hypotheses, where sparse and dense functional data are considered in a unified framework. We find a phase transition in the asymptotic null distributions and the orders of detectable alternatives from sparse to dense functional data. Specifically, the tests proposed can detect alternatives of √n‐order when the number of repeated measurements per curve is of an order larger than urn:x-wiley:13697412:media:rssb12246:rssb12246-math-0001 with n being the number of curves. The transition points urn:x-wiley:13697412:media:rssb12246:rssb12246-math-0002 for pointwise and simultaneous tests are different and both are smaller than the transition point in the estimation problem. Simulation studies and real data analyses are conducted to demonstrate the methods proposed

Transcriptome sequence analysis of an ornamental plant, Ananas comosus var. bracteatus, revealed the potential unigenes involved in terpenoid and phenylpropanoid biosynthesis.

Ananas comosus var. bracteatus (Red Pineapple) is an important ornamental plant for its colorful leaves and decorative red fruits. Because of its complex genome, it is difficult to understand the molecular mechanisms involved in the growth and development. Thus high-throughput transcriptome sequencing of Ananas comosus var. bracteatus is necessary to generate large quantities of transcript sequences for the purpose of gene discovery and functional genomic studies.The Ananas comosus var. bracteatus transcriptome was sequenced by the Illumina paired-end sequencing technology. We obtained a total of 23.5 million high quality sequencing reads, 1,555,808 contigs and 41,052 unigenes. In total 41,052 unigenes of Ananas comosus var. bracteatus, 23,275 unigenes were annotated in the NCBI non-redundant protein database and 23,134 unigenes were annotated in the Swiss-Port database. Out of these, 17,748 and 8,505 unigenes were assigned to gene ontology categories and clusters of orthologous groups, respectively. Functional annotation against Kyoto Encyclopedia of Genes and Genomes Pathway database identified 5,825 unigenes which were mapped to 117 pathways. The assembly predicted many unigenes that were previously unknown. The annotated unigenes were compared against pineapple, rice, maize, Arabidopsis, and sorghum. Unigenes that did not match any of those five sequence datasets are considered to be Ananas comosus var. bracteatus unique. We predicted unigenes encoding enzymes involved in terpenoid and phenylpropanoid biosynthesis.The sequence data provide the most comprehensive transcriptomic resource currently available for Ananas comosus var. bracteatus. To our knowledge; this is the first report on the de novo transcriptome sequencing of the Ananas comosus var. bracteatus. Unigenes obtained in this study, may help improve future gene expression, genetic and genomics studies in Ananas comosus var. bracteatus

Summary of Illumina transcriptome assembly for <i>A</i>. <i>comosus</i> var. <i>bracteatus</i>.

<p>Summary of Illumina transcriptome assembly for <i>A</i>. <i>comosus</i> var. <i>bracteatus</i>.</p

Distribution of Conservation between <i>A</i>. <i>comosus</i> var. <i>bracteatus</i> unigenes and pineapple EST sequences based on tBLASTX scores.

<p>Distribution of Conservation between <i>A</i>. <i>comosus</i> var. <i>bracteatus</i> unigenes and pineapple EST sequences based on tBLASTX scores.</p

Overview of the <i>A</i>. <i>comosus</i> var. <i>bracteatus</i> transcriptome sequencing and assembly.

<p>(A) Length distribution of <i>A</i>. <i>comosus</i> var. <i>bracteatus</i> transcripts. (B) Size distribution of <i>A</i>. <i>comosus</i> var. <i>bracteatus</i> unigenes. (C) Log-log plot showing the dependence of unigene lengths on the number of reads assembled into each unigene.</p

The Phenylpropanoid biosynthesis.

<p>The A. comosus var. bracteatus transcripts encoding enzymes (highlighted) involved in the pathway was identified by BLASTx (E-value of less than 10–5). Numbers in bracket are the total number of unigenes encode for the enzyme.</p

The Flavonoid biosynthesis.

<p>The <i>A</i>. <i>comosus</i> var. <i>bracteatus</i> transcripts encoding enzymes (highlighted) involved in the pathway was identified by BLASTx (E-value of less than 10^-5). Numbers in bracket are the total number of unigenes encode for the enzyme.</p