20 Years of Calm. Cool. Collected. With the Culex®

This year marks the 20th anniversary of the commercial release of the Culex Automated Blood Sampling System.  We've made some great progress over the years, and we're so thankful to you for making low-stress, automated blood sampling a part of your drug development process. We'll be celebrating all things Culex during the week of October 7th, and our webinar series on October 10th is part of that celebration. Tune in to hear presentations from Culex users sharing some of their best practices and applications.  We’ll keep updating the list below, but make sure to RSVP so we can keep you informed.

 

Tuesday, October 8th, 2019

 Time (EDT)   Presentation Title
 9:00am  Oh, the things we can do! A review of the applications where Culex can help get better data from fewer animals
 9:30am  Reducing Food Contamination in Rodent Metabolic Caging
 10:30am  Automated Blood Sampling and Dog Telemetry—3Rs Refinement and an Improvement to Preclinical Cardiovascular Safety Assessment
 1:30pm  You’ve got questions, we’ve got answers. A review of some of the most frequently asked questions when working   with the Culex
 2:00pm  As the Pig Turns—Swine PK using the Culex
 2:30pm  What’s new with the Culex? Updates on current projects to help you get the best study data

Wednesday, October 9th, 2019

 Time (EDT)   Presentation Title
 9:00am  Tip Matters: Jugular Vein Catheter Patency in Sprague-Dawley Rats
 9:30am  Development of an in-house harness for use on the Culex System
 10:00am  How the Culex Came to Be
 10:30am  KEYNOTE: 18 Years of Culex Experience- a retrospective on using the Culex for drug development
 11:30am  Advancing Medicine One Drop of Blood at a Time: A word from BASi’s Founders

Tuesday, 10/8 9:00am EDT

Oh, the things we can do! A review of the applications where Culex can help get better data from fewer animals

By Candace Rohde-Johnson, BASi

For more than 20 years, the Culex has been used as an automated blood sampling device, but it can do so much more than just sampling blood. Explore a range of pharmacology applications possible with the Culex, including interstitial fluid sampling, bile, first pass metabolism models, optogenetics, behavioral pharmacology, safety pharmacology and more. Get familiar with the range of studies that can be performed with low-stress, freely moving animals.

Tuesday, 10/8 9:30am EDT

Reducing Food Contamination in Rodent Metabolic Caging

By Pam Lachcik, BASi

Laboratory rats have long been used as a proxy to study human biological processes and serve a particularly important function in preclinical drug development and biomarker discovery. Biotransformations, uptake, and production of metabolites are all biochemical pathways of metabolism which can be studied by employing metabolic caging that allows for the separate collection of both feces and urine. A common problem with metabolic caging is contamination with food particles that drop through the mesh cage flooring. Although uncommon, it is possible for food proteins to bind to protein biomarkers which can decrease the amount of biomarkers found during routine analysis and thus misrepresent results. Here, two methods were employed to decrease the amount of contamination. First, a wire-barred insert was developed to slide into the cage’s food hopper. Second, a diet gel was compared to a traditional pelleted diet. The urine output was then ranked on a scale from 1-5 each for volume, clarity, debris, and color with 1 being the best.  The wire-barred insert deterred most subjects from removing all the food from their food hoppers at once. When using a pelleted diet, the barred insert (N=14) marginally increased the urine quality (4.1 to 3.5) when compared to an open food hopper. Exchanging pelleted diet (N=15) for diet gel (N=10) in an open food hopper also improved the average urine quality (4.1 to 2.1). Finally, by using the wire-barred insert and the diet gel simultaneously (N=10), the average urine quality was greatly improved (4.1 to 1.6). In conclusion, utilizing both of these methods decreases food contamination and generates better quality samples.

Tuesday, 10/8 10:30-11:30am EDT

Automated Blood Sampling and Dog Telemetry—3Rs Refinement and an Improvement to Preclinical Cardiovascular Safety Assessment

By Amanda Wilsey and Dr. Yevgeniya Koshman, AbbVie Inc.

A successful integration of the automated blood sampling (ABS) and canine telemetry system has been recently implemented by AbbVie’s Safety Pharmacology team as part of the new standard screening paradigm. The new system facilitates concomitant collection of cardiovascular data with blood samples for determination of drug concentrations and potentially other biochemical measures (i.e. cytokines) in the same animal without handling artifact.  In an efforts to reduce the number of animals used in the drug discovery and safety assessment process, our team has shown feasibility in combining dose escalating pharmacokinetic (PK) and cardiovascular (CV) assessment in a single design, increasing the impact of CV data by improving the ability to define the exposure-response relationship. 

Tuesday, 10/8 1:30pm EDT

You’ve got questions, we’ve got answers. A review of some of the most frequently asked questions when working with the Culex

By Shelly Carballo, BASi

Do the rats get dizzy? How many times can I use my Culex tubing set? What enrichment can be used with the Raturn? What are the collar and harness options for the Raturn and Culex tubing set connections? We will walk through answers to common questions, but also leave plenty of time to address any live questions! Enquiring minds welcome.

Tuesday, 10/8 2:00pm EDT

As the Pig Turns—Swine PK using the Culex

By Robyn McCain, Purdue University

Designing studies with pigs can often be a challenge of monumental proportions. How do you collect the sample without changing the composition of that sample? Pigs are often considered one of the most intelligent animals in the research community. They have the aptitude of a 3 year old human child. And often just like at home when it is time to dose your toddler they run kicking and screaming. How do you do this with pigs and get what you need for your studies. Purdue University uses the Culex-L for the majority of it's PK/PD studies in swine. Today we will discuss the options in which this system is used as well as the sometimes fun challenges that go into making pigs "fun". Imagine all you could do for your studies as the pig turns!

Tuesday, 10/8 2:30 EDT 

What’s new with the Culex? Updates on current projects to help you get the best study data

By Scott Peters, BASi

Learn about some of our recent developments to improve your studies, including updates to tubing sets (one piece and two piece), vial changes, cages, and integrations with rodent catheter access ports and buttons. Get a little preview of what’s in the works and what is coming soon.

Wednesday, 10/9 9:00am EDT

Tip Matters: Jugular Vein Catheter Patency in Sprague-Dawley Rats

By Haley Roeder, BASi

Surgical implantation of jugular vein catheters (JVCs) facilitates central venous access in preclinical models. Use of JVCs can enhance animal welfare and potentially reduce the number of animals needed, along with refining study design to get better, translatable data. Patency, or bi-directional flow, defines the functional life of a JVC; therefore, it is important to examine potentially contributing factors, such as catheter tip shape and maintenance. Rat JVCs are widely accepted and used, however, design and manufacturing process vary among institutions with limited scientific evidence surrounding the efficacy of either factor. This study compares patency of JVCs from three different manufacturers. Each JVC is made of 3-french polyurethane (PU); two have a rounded tip, one has a bullet tip, and one has a straight-cut tip. 34 male 280g Sprague-Dawley rats were randomly assigned to one of four groups and catheterized via the right jugular vein. Catheter patency was evaluated every 3-4 days for 28 days. Catheters were deemed fully patent if blood was withdrawn during the initial attempt. If blood was not immediately withdrawn, 0.1 ml saline infusion was followed by a second attempt. If successful, catheters were considered partially patent. If unsuccessful, catheters were considered non-patent. After 28 days, 70% of one rounded tip, 60% of the other rounded tip, 89% of the bullet tip, and 0% of the straight-cut catheters were considered fully or partially patent. Bullet-tip catheters showed sporadic patency and would be advised for manual sampling only, but the rounded tip would be advised if using an automated blood sampling  (ABS) system.

Wednesday, 10/9 9:30am EDT

Development of an in-house harness for use on the Culex System

By Dr. Jaya Jayaseelan and Dr David Shackleford, Monash University

(Presented by Shelly Carballo, BASi)

Monash Institute of Pharmaceutical Sciences (MIPS) designed a robust, DIY harness which can be made of simple materials and a pair of scissors. Originally designed for use with swivel systems, the harness was easily adapted for use with the Raturn and is the only harness/collar used in their tethered animal studies. These harnesses were developed with animal comfort and welfare as the primary concern, but they are also easy to make and economical. MIPS  will share more about the materials, care, design, and pros/cons in this presentation. You’ll also have access to their pattern to make your own!

Wednesday, 10/9 10:00am EDT

Reconsidering the Bio in Bioanalytical Systems: the Origins of In Vivo Sampling within an Analytical Instrument Company.​

By Candice Kissinger, Co-Founder and Chief Scientific Officer, Phlebotics Inc.

The growth of BASi from a tiny startup that had hatched from academic research into a publicly-traded pharmaceutical services company was based predominantly on its expertise in analytical chemistry.  This  included electrochemistry and liquid chromatography with special emphasis on analysis of materials with a biological origin.  Determination of neurotransmitters in brain tissue and catecholamines in blood were among the applications developed by the company which helped to propel its rapid growth.  The company was originally focused on manufacture of analytical instruments but soon expanded into a GLP contract services organization capable of serving pharmaceutical clients seeking analytical support for clinical trials.  The addition of an in vivo sampling product line to this mix was not a logical extension.  This narrative presentation will outline the origins of the Culex blood sampling system, beginning with predecessor instruments created for in vivo microdialysis.

Wednesday, 10/9 10:30 - 11:30am EDT

KEYNOTE: 18 Years of Culex Experience- a retrospective on using the Culex for drug development

By Dr. Horst Beier, Grünenthal

In summer 2001, Grünenthal’s first Culex was set into action (one of the first European Culex labs). The team was curious and excited. The major developments from that moment on will be presented. This includes implementation of arterial blood sampling, repeated dosing before Empis became available, combination with brain microdialysis, microdialysis in the peritoneal cavity as surrogate for free blood concentrations and as an option to investigate pharmacokinetics in mice, optimal use of the "no waste blood" sampling, and PK/PD with a behavioral PD model. The presentation will be a journey through these developments.

Wednesday, 10/9 11:30am EDT

Advancing Medicine One Drop of Blood at a Time: A word from BASi’s Founders

By  Dr. Peter Kissinger, BASi and Phlebotics

How do we follow the dynamics of chemical changes in vivo on short time scales? It all began with euthanasia in the 1970s and then the first implanted electrochemical sensors. It evolved to in vivo microdialysis sampling in anesthetized animals in the 1980s. This led to microdialysis in awake freely moving animals in the 1990s. This then mutated into automated blood sampling in freely moving mice and rats and then soon to swine, primates and humans. Workflows for processing ADME/PK samples have improved with automation of their own. Thus many more samples can be collected and processed both more quickly and with confidence compared to the laborious manual work in the 1970s. Better coordination of animal models with bioanalytical workflows enhances the productivity for both. This history and projections for the logical next steps will be explored in this presentation. We now have the tools to optimize dosing in individual patients, but not yet cost-effectively. Soon, perhaps?