Small Volume Fraction Collection

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{{LSApp
{{LSApp
-
   |name        = Collect PAL
+
   |name        = Small Volume Fraction Collection -- Collect PAL
-
   |image      = Collect1.png
+
   |image      = CP_96_Well_1.jpg
-
   |type        = '''Purification'''
+
   |type        = Fraction Collection
-
  |id          =
+
   |description = “0” Loss, “0” Drip Fraction Collection using a LEAP designed inverted syringe equipped with a hollow plunger and custom syringe holder.  This unique and patent-pending design allows for collection to continue during well-to-well movements.  Typical Applications involve isolating and collecting sample into precoated scintillation plates (LUMA by Perkin Elmer for instance) with a finely tuned spread of the flow over the wells of a plate.  With this data a Radio Chromatogram can be reproduced with the plate data as read by a scintillation counter.
-
   |description = Collect PAL
+
[See: http://en.wikipedia.org/wiki/Scintillation_counter]
 +
The integration of the Collect PAL with LC-MS and UPLC systems is achieved via LEAP Shell and the Collect PAL application.
}}
}}
=== Overview ===
=== Overview ===
-
The Collect PAL fraction collection system as shown can hold up to 24-shallow well plates and collect into either 96-well or 384-well plates.  It is shown with its waste drain and high pressure valve set up.  With this valve it is able to use down to 0.005” id PEEK tubing.
+
The Collect PAL was designed through collaborative efforts with researchers at BMS (Princeton) and Merck-Frosst (Montreal).  Initial instrument parameters defined a simple fraction collector application capable of collecting into 96-well plates for radiolabeled metabolite collection and identification.  Very quickly, however, it became apparent that the modern biotransformation laboratory required a more stringent and precise application and instrument – especially due to the presence of radiolabeled compounds and the risk of unnecessary exposure.  The use of precoated plates such as LUMAWhat resulted is an instrument that has a no loss, no drip operation and an easy to use, fully operator-designed interface.
-
Compact in size, the Collect PAL covers a bench area of only 28”x28” and has a height of only 24” to the top of its Z-arm.
+
The Collect PAL offers environmental control for samples and the precision to deliver into a 384-well plate at 3 sec/well. With appropriate conditions the Collect PAL can pierce septa, plate seals, or capmats and deliver the sample into the well with a touch off and retract feature.
-
== Significant Markets ==
+
At the 2008 ISSX Meeting held in San Diego, California, colleagues from BMS presented their findings on the Collect PAL. (See poster and ppt file in Download Section).  The responses from the research results and the research community have been very positive.  With the help and insight of the researchers we have made several modifications to the original design to make the Collect PAL more compatible with the small volume collection needs of research.  We have employed a 2-position, 6-port selection valve which accomplishes two things immediately. 1) we can now collect using 5/1000ths tubing and 2) we have further reduced the path volume of the sample to the collection plate. Results from our collaboration with Merck-Frosst researchers pushed us to collection into 384-well plates with documented 3sec/well collection.
-
====DMPK====
+
-
Drug Metabolism & PharmacoKinetics studies
+
-
a range of stable isotopically-labeled products that can provide accurate and non-radioactive in vivo studies of both nutrition and metabolism. Compounds labeled with stable isotopes like Carbon-13, Nitrogen-15, Deuterium and others can be identified and measured using techniques such as MRI and MRS
+
-
====ADMET====
+
-
Adsorption ,Distribution, Metabolism, Excretion, and Toxicity – drug properties – are fundamental pharmacokinetic properties that determine the in vivo efficacy of a drug, together with its intrinsic biological activity on the target.  
+
-
Metabolomics (from Wikipedia – this section is a good read) is the "systematic study of the unique chemical fingerprints that specific cellular processes leave behind" - specifically, the study of their small-molecule metabolite profiles[1]. The metabolome represents the collection of all metabolites in a biological organism, which are the end products of its gene expression. Thus, while mRNA gene expression data and proteomic analyses do not tell the whole story of what might be happening in a cell, metabolic profiling can give an instantaneous snapshot of the physiology of that cell. One of the challenges of systems biology and functional genomics is to integrate proteomic, transcriptomic, and metabolomic information to give a more complete picture of living organisms
+
-
== Key Features ==
+
Flexibility and convenience are two additional factors that make the Collect PAL application easy to use.  The Collect PAL cart is a rugged and chemically resistant cart on locking casters which allows the users to wheel the Collect PAL up to any UPLC or LC-MS instrument and tap into the flow via a splitter.  The Collect PAL coordinates with the LC system by contact closure – coordinating the injection with the start time of the application.  Defined parameters of delay time, collection time per well, and number of fractions to collect are all user determined.  In addition to the cart, the Collect PAL offers a Fast Connect cable option which allows the users to keep contact lines connected to each instrument needed and via a simple plug and play the system can be attached to the required contact inputs and outputs.
-
*  Zero Loss Collection – most fraction collectors either are a drop-type or a solenoid driven-type.
+
-
*  Zero Drips, Zero Spills
+
-
* The drop type fraction collector simply flows the effluent through tubing to a movable arm and positions the tubing over a well or tube and stays in that position for a specified time until moving to the next collection site.  The main concern with this type of fraction collection is the complete lack of control over volume in the fraction site and, more importantly, the placement of each and every drop in a tube.  There should be concern that sample can be lost during the “in-between” of sites during a move.
+
-
*  The solenoid drive fraction collector solves the drop between sites problem by quickly switching a solenoid valve off/on during the move between wells.  Drip solved, but now valuable sample during that movement is sent to a waste stream.  Sample is lost to the waste.
+
-
*  Neither type of fraction collection option protects what is most important – the sample -- and provides a safe environment for the researcher.
+
 +
=== Significant Markets  and Research Focus===
 +
* Metabolic Profiling Groups
 +
* DMPK
 +
* Radiolabel Compound Characterization
-
[[Image:Collect2.png|350px|thumb|left|Inverted Syringe]]
+
* ADMET
-
LEAP employs an inverted syringe technology, design, and control that eliminates the drops between sites and also eliminates the lost sample to waste of both drip and solenoid type fraction collectors.
+
 +
* Metabolomics
 +
* Impurity Identification
-
*  Ability to collect through septa, capmats, plate seals.  No one else can do this with ZERO LOSS. – Beats Solenoid fraction collectors
 
-
*  Collect a constant, precise, user-defined volume per well or tube
 
-
*  Touch-off Fraction Collection with LEAP SHELL you can send the needle to a specified height and then retract; offering a touch-off fraction collection within a well.
 
-
*  3 sec/well fraction collection available in 384-well plates. 
 
-
*  Deep-well, shallow-well or 2-mL vial collection set up.
 
-
*  2 Stack Configuration – Up to 12 plates or trays
 
-
*  Max number of fractions per injection – Remember that you can only collect within the same collection plane.  The maximum number of plates per injection available for collection = 4
+
=== LEAP's Approach ===
-
*  2-mL Vials – 4x54 = 216
+
-
*  96-Well Plate – 4x96 = 384
+
-
*  384-Well Plate – 4x384 = 1536
+
 +
[[Image:CP_96_Well_6.jpg|200px|thumb|left|Collect PAL shown with one 6-Drawer CoolStack]]
 +
             
 +
The Collect PAL is designed to accommodate the needs of the researcher with valuable sample and small volume collection requirements.  With our innovation and collaboration we have come up with an instrument that loses no sample during the defined collection time window and can distribute the desired sample into wells accurately and as quickly as 3sec/well.  The process requires sample collection continuing even during a well-to-well move.  By quickly aspirating a set volume just before a move command is initiated, the barrel of the syringe becomes a temporary reservoir for the desired compound stream.  Once the needle is over or in the new well, the syringe dispenses the barrel contents into the well and collection continues for the specified time.  The aspiration step also pulls the small amount in the outlet line and needle back into the needle and eliminates any drip that may shake off during the move.  The efficiency and effectiveness of this design is unique and is not possible with other syringe, solenoid, or drop collector options.
 +
Another user-defined requirement was that the collection had to be able to occur into covered wells – either with a plate seal or by a capmat.  At first these defining parameters appeared to be insurmountable.  With a little research it became more obvious that a new design needed to be employed.  Most market fraction collectors can be dissected into two camps – drop collectors or solenoid.
 +
Drop Collectors do just that; i.e. drip or flow or spray sample out of a tube and into a vessel.  During the collection time window the flow rate is diverted to an outlet (usually a needle or even just tubing) that is hovering over an open collection vessel.  Flow is never stopped during the time window and chances are very good that some percentage of the drops or flow or spray will not hit a well during a “move to next well” command from the fraction collector software. Sample can contaminate the instrument, plate, etc.
 +
Solenoid Based fraction collectors offer no drip between sites, yet sample is lost during the “move to next well” command.  For that brief span of time that the head moves from well-to-well the solenoid is deactivated and flow goes into waste stream.  The head moves and situates over the next vessel.  Then the solenoid is activated back to the collection path.  Sample is lost during every move during collection and is, for the most part unrecoverable.
 +
Neither type of typical fraction collector can be easily set up to collect through a covered plate or through septa covered vials.  To do this an extra Z-Motion is required and the fraction collector needs a piercing probe or needle, a push off component, and time to accomplish the task.
-
[[Image:Collect7.png|350px|thumb|left|LEAP Shell Software]]
+
The Collect PAL features penetration and retract parameters that allow the needle to go below the “surface” plane of the plate for the first second of collection and then retract slightly, but not above the seal to complete the collection time.  This allows the collection to occur in a completely sealed plate and provides even greater protection of the sample.
-
== Software ==
+
As our user numbers grow we find that our modularity and flexibility also continue to grow.  We are already working on version 2 of the Collect PAL series.
-
* LEAP SHELL CONTROL
+
-
* User-Friendly Interface
+
-
* Total Parameter Control
+
-
* Multiple Method Recall
+
-
* Direct Integration with most LC-MS systems
+
-
* Living Sample List
+
-
* Priority Scheduling
+
-
* Import/Export Run Lists
+
-
* Multiple Methods Available per Run
+
 +
[[Image:CP_Head_ and_Valve_3.jpg|200px|thumb|left|Collect PAL Head and Syringe Close Up]]
 +
<br/><br/>
 +
=== Software Control ===
 +
The Collect PAL operates under a LEAP SHELL application and coordination via contact closures with LC systems.
 +
 +
== PHOTOS of Configurations ==
 +
<gallery>
 +
  Image:CP_2mL_3.jpg  | Collect PAL with 2mL vials in a Stack
 +
  Image: CP_384_Well_2.jpg  | Collect PAL with 384-Well Plates in 2 Stack Configuration
 +
  Image: CP_Close_Needle1.jpg  | Collect PAL Close Up Collection
 +
  Image: CP_Head_and_Valve_ 1.jpg  | Collect PAL Head and Valve Assembly
 +
</gallery>
 +
 +
== LEAP Shell Screenshots ==
 +
 +
<gallery>
 +
  Image: 1_Opening_Screen.jpg  | LEAP Shell Opening Splash Sign In
 +
  Image: 4_Method_Default_Page.jpg  | Method Parameters Defined by User
 +
  Image: 18_Samples_Add.jpg  | Building a Sample List
 +
  Image: 25_Queue_First.jpg  | Run Queue Loaded and Ready
 +
</gallery>
 +
 +
== Video ==
 +
 +
Coming Soon to You Tube.
 +
 +
== Useful Links and Resources ==
 +
 +
American Society for Mass Spectrometry  [http://www.asms.org/]
 +
 +
International Isotope Society [http://www.intl-isotope-soc.org/]
 +
 +
International Society for the Study of Xenobiotics  [http://www.issx.org/i4a/pages/index.cfm?pageid=1]
 +
 +
== Other Reference material ==
 +
 +
*[[:Image:BMS CollectPAL ISSX.pdf | 2008 ISSX BMS Poster]]
 +
*[[:Image:ISSX2008-CollectPAL-Print-Barros-1.pdf | Extended Mix - 2008 ISSX BMS Poster]]
 +
*[[:Image:Animate_Cartoon_explaining_Collection.pps | Slideshow displaying stages for ZERO LOSS, ZERO DRIP Move and Collection ]]
 +
*[[:Image:Collect_PAL_for_Slideshow_WIKI.pdf | Collect PAL Configurations ]]
 +
*[[:Image:Collect_PAL_Flyer.pdf | Collect PAL Configurations ]]
 +
 +
== Contact LEAP ==
 +
 +
* [http://www.leaptec.com/ LEAP Technologies, Inc.]
 +
 +
 +
[[Category: Fraction Collection]]
 +
[[Category: Metabolite Identification]]
 +
[[Category: DMPK]]
 +
[[Category: ADMET]]
 +
[[Category: Metabolic Profiling]]
 +
[[Category: Radiolabel Compound]]
 +
[[Category: Radiolabel Chromatogram]]

Revision as of 23:01, 6 April 2009

Small Volume Fraction Collection -- Collect PAL
Application Type
  Fraction Collection
Application ID
  {{{id}}}
Description
  “0” Loss, “0” Drip Fraction Collection using a LEAP designed inverted syringe equipped with a hollow plunger and custom syringe holder. This unique and patent-pending design allows for collection to continue during well-to-well movements. Typical Applications involve isolating and collecting sample into precoated scintillation plates (LUMA by Perkin Elmer for instance) with a finely tuned spread of the flow over the wells of a plate. With this data a Radio Chromatogram can be reproduced with the plate data as read by a scintillation counter.

[See: http://en.wikipedia.org/wiki/Scintillation_counter] The integration of the Collect PAL with LC-MS and UPLC systems is achieved via LEAP Shell and the Collect PAL application.

Contents

Overview

The Collect PAL was designed through collaborative efforts with researchers at BMS (Princeton) and Merck-Frosst (Montreal). Initial instrument parameters defined a simple fraction collector application capable of collecting into 96-well plates for radiolabeled metabolite collection and identification. Very quickly, however, it became apparent that the modern biotransformation laboratory required a more stringent and precise application and instrument – especially due to the presence of radiolabeled compounds and the risk of unnecessary exposure. The use of precoated plates such as LUMAWhat resulted is an instrument that has a no loss, no drip operation and an easy to use, fully operator-designed interface.

The Collect PAL offers environmental control for samples and the precision to deliver into a 384-well plate at 3 sec/well. With appropriate conditions the Collect PAL can pierce septa, plate seals, or capmats and deliver the sample into the well with a touch off and retract feature.

At the 2008 ISSX Meeting held in San Diego, California, colleagues from BMS presented their findings on the Collect PAL. (See poster and ppt file in Download Section). The responses from the research results and the research community have been very positive. With the help and insight of the researchers we have made several modifications to the original design to make the Collect PAL more compatible with the small volume collection needs of research. We have employed a 2-position, 6-port selection valve which accomplishes two things immediately. 1) we can now collect using 5/1000ths tubing and 2) we have further reduced the path volume of the sample to the collection plate. Results from our collaboration with Merck-Frosst researchers pushed us to collection into 384-well plates with documented 3sec/well collection.

Flexibility and convenience are two additional factors that make the Collect PAL application easy to use. The Collect PAL cart is a rugged and chemically resistant cart on locking casters which allows the users to wheel the Collect PAL up to any UPLC or LC-MS instrument and tap into the flow via a splitter. The Collect PAL coordinates with the LC system by contact closure – coordinating the injection with the start time of the application. Defined parameters of delay time, collection time per well, and number of fractions to collect are all user determined. In addition to the cart, the Collect PAL offers a Fast Connect cable option which allows the users to keep contact lines connected to each instrument needed and via a simple plug and play the system can be attached to the required contact inputs and outputs.

Significant Markets and Research Focus

  • Metabolic Profiling Groups
  • DMPK
  • Radiolabel Compound Characterization
  • ADMET
  • Metabolomics
  • Impurity Identification


LEAP's Approach

Collect PAL shown with one 6-Drawer CoolStack
Collect PAL shown with one 6-Drawer CoolStack

The Collect PAL is designed to accommodate the needs of the researcher with valuable sample and small volume collection requirements. With our innovation and collaboration we have come up with an instrument that loses no sample during the defined collection time window and can distribute the desired sample into wells accurately and as quickly as 3sec/well. The process requires sample collection continuing even during a well-to-well move. By quickly aspirating a set volume just before a move command is initiated, the barrel of the syringe becomes a temporary reservoir for the desired compound stream. Once the needle is over or in the new well, the syringe dispenses the barrel contents into the well and collection continues for the specified time. The aspiration step also pulls the small amount in the outlet line and needle back into the needle and eliminates any drip that may shake off during the move. The efficiency and effectiveness of this design is unique and is not possible with other syringe, solenoid, or drop collector options.

Another user-defined requirement was that the collection had to be able to occur into covered wells – either with a plate seal or by a capmat. At first these defining parameters appeared to be insurmountable. With a little research it became more obvious that a new design needed to be employed. Most market fraction collectors can be dissected into two camps – drop collectors or solenoid.

Drop Collectors do just that; i.e. drip or flow or spray sample out of a tube and into a vessel. During the collection time window the flow rate is diverted to an outlet (usually a needle or even just tubing) that is hovering over an open collection vessel. Flow is never stopped during the time window and chances are very good that some percentage of the drops or flow or spray will not hit a well during a “move to next well” command from the fraction collector software. Sample can contaminate the instrument, plate, etc.

Solenoid Based fraction collectors offer no drip between sites, yet sample is lost during the “move to next well” command. For that brief span of time that the head moves from well-to-well the solenoid is deactivated and flow goes into waste stream. The head moves and situates over the next vessel. Then the solenoid is activated back to the collection path. Sample is lost during every move during collection and is, for the most part unrecoverable.

Neither type of typical fraction collector can be easily set up to collect through a covered plate or through septa covered vials. To do this an extra Z-Motion is required and the fraction collector needs a piercing probe or needle, a push off component, and time to accomplish the task.

The Collect PAL features penetration and retract parameters that allow the needle to go below the “surface” plane of the plate for the first second of collection and then retract slightly, but not above the seal to complete the collection time. This allows the collection to occur in a completely sealed plate and provides even greater protection of the sample.

As our user numbers grow we find that our modularity and flexibility also continue to grow. We are already working on version 2 of the Collect PAL series.

Collect PAL Head and Syringe Close Up
Collect PAL Head and Syringe Close Up



Software Control

The Collect PAL operates under a LEAP SHELL application and coordination via contact closures with LC systems.


PHOTOS of Configurations

Collect PAL with 2mL vials in a Stack

Collect PAL with 384-Well Plates in 2 Stack Configuration

Collect PAL Close Up Collection

Collect PAL Head and Valve Assembly

LEAP Shell Screenshots

LEAP Shell Opening Splash Sign In

Method Parameters Defined by User

Building a Sample List

Run Queue Loaded and Ready

Video

Coming Soon to You Tube.

Useful Links and Resources

American Society for Mass Spectrometry [1]

International Isotope Society [2]

International Society for the Study of Xenobiotics [3]

Other Reference material

Contact LEAP


Screenshots

Collect PAL System

Collect PAL

Collect PAL

Collect PAL

Collect PAL

Collect PAL

Collect PAL

Collect PAL


Contact LEAP

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