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As Small-Animal Imaging Grows, Caliper and Invitrogen to Build Custom Fluorescence Kits

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Caliper Life Sciences and Invitrogen business unit Molecular Probes this week said they plan to co-develop and distribute custom fluorescence labeling kits for use with Caliper’s IVIS in vivo optical imaging systems.
 
According to Caliper, the deal will help the company stay on top of what it sees as a growing market for fluorescence-based small-animal imaging in drug discovery.
 
In addition, the agreement could lead to similar co-marketing pacts between Caliper and Invitrogen as Caliper looks to update the fluorescence capabilities of the IVIS platform.
 
Under the terms of the agreement, Caliper and Molecular Probes will develop fluorescence labeling kits optimized for use with Caliper’s IVIS platforms and based on Molecular Probes’ Alexa Fluor 680 and 750 dyes.
 
According to Mark Roskey, Caliper’s vice president for reagents and applied biology, Caliper will sell the specialized dye kits under its VivoFluor brand name. It will sell them independent of its IVIS platforms but, considering that they are optimized for use with the instrument, the company will also aim to bundle the products.
 
“A number of customers had been playing around with different fluorescent dyes, including the AlexaFluor dyes, on the IVIS,” Roskey told CBA News last week. “We had seen from our customer base some nice success with these dyes. We partnered with the Molecular Probes division of Invitrogen, started to generate some data ourselves, and found that they were working really well, so [we] decided to build them up into a convenient kit for our customers.”
 
One of the ways Caliper has optimized the fluorescence dyes for IVIS is to offer appropriate quantities that a researcher would need in a typical small animal fluorescence imaging application, Roskey said.
 
“We’ve also worked to makes sure our instrument hardware is aligned optimally with the excitation and emission characteristics of these dyes,” he said.
 
Caliper, through its recently acquired Xenogen arm, sells several platforms for small-animal imaging under the IVIS brand. These include the IVIS 3D, 200, 100, Spectrum, and Lumina.
 
The IVIS is the newest of these instruments and allows users to detect bioluminescence and fluorescence, instead of luminescence only, from small animals. According to Caliper’s website, the instrument features 28 filters from 430 nm to 850 nm, an optical switch in the fluorescence illumination path that allows reflection-mode or transmission-mode illumination, and 3-D diffuse tomographic reconstruction for both fluorescence and bioluminescence imaging experiments.
 
Roskey said that about half of the IVIS systems in the field are capable of fluorescence imaging, and that a “solid majority” of those customers are doing fluorescence imaging applications.
 
Before it was acquired by Caliper, Xenogen sold reagent kits for use with IVIS, but the kits consisted primarily of bioluminescent cell lines that customers would use to perform xenograft experiments in small animals, Roskey said.
 
“The key applications are still bioluminescence, but people are becoming increasingly interested in fluorescence in vivo imaging,” Roskey said. “The technology hasn’t been working that great until recently, but now the ability to quantitate fluorescence in vivo and … to accurately detect fluorescence at greater depths than before is causing more and more people to develop applications using fluorescent agents.”
 

“On the fluorescence side our partner at the moment is Molecular Probes, and we’re continuing to investigate other dyes and fluorescent reporters with them.”

Bioluminescence has typically been the modality of choice for small-animal imaging because it has traditionally offered superior sensitivity to most other methods. Scientists are interested in small-animal fluorescence imaging, however, because it provides a different type of data. But until recently, fluorescent labels were not advanced enough to provide the type of sensitivity needed to image small animals – in other words, through several layers of tissue.
 
“Most of the imaging you do with bioluminescence is focused on transcriptional readouts,” Roskey said. “You put a luciferase gene behind an active promoter, and you can look at the on and off of different genes. That provides you with one type of data.
 
“But what you don’t usually get at with luminescence so much is looking at a specific analyte in an animal – for example, at a receptor or a peptide, or labeling and antibody,” he added. “This is more conveniently done with a fluorophore than with some type of bioluminescent approach.”
 
Combining these approaches, then, allows scientists to track tumor cells or follow the activation of specific genes using bioluminescence, and then quantify the density of specific proteins within said tumor cells – all in the context of a living animal.
 
Most researchers use IVIS to image mice or rats, but the system is capable of imaging larger animals such as rabbits and, in one case, chimpanzees, Roskey said. On the other end of the spectrum, the instrument has the ability to image cells or very small organisms such as zebrafish in well plates, but the platform is “really designed for small animals” and does not actively compete in these markets, he added.
 
Caliper intends to continue beefing up the fluorescence capabilities of the IVIS platforms to follow what it sees as a trend in the marketplace. Accordingly, the company will also continue to create and optimize both fluorescent and bioluminescent reagents to match its instrumentation development pipeline.
 
“On the fluorescence side our partner at the moment is Molecular Probes, and we’re continuing to investigate other dyes and fluorescent reporters with them,” Roskey said. “There will be additional kits in the future, but I can’t be more specific than that.”
 

Caliper announced its intent to acquire Xenogen in February, saying that the company would be a crucial piece in an “in vitro-to-in vivo continuum” of drug-discovery products and services.

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