Via a catheter, ALZET pumps can deliver substances into the venous or arterial circulation, into the brain, or into any organ, lumen, or solid tissue (List of major routes of administration). Attachment to a catheter does not alter the delivery rate of the pump. A variety of catheter materials have been used successfully with the pumps. Click here for information about compatibility of ALZET specialized catheters s solvents/vehicles.
To operate the pump with a catheter, perform the following steps.
- 200 µl & 2 ml Models: Remove the translucent
cap from the end of the flow moderator, revealing a short stainless
steel tube protruding from the white flange.
100 µl Models: Remove and discard the white plastic flange using scissors or pliers. In doing so, be careful not to bend or crush the stainless steel tube. These three models are designed to be as space efficient as possible for use in smaller animals, so were designed without a translucent cap on the flow moderator. (see method)
- Attach the flow moderator to a piece of catheter tubing. The catheter
should have an inside diameter (ID) of approximately 0.76 mm (equal
to 0.030 inches). Polyethylene tubing, commonly called PE-60 (ID =
0.76 mm), is a good choice for most applications. After attachment,
the catheter should cover the entire length of the stainless steel
tube above the white flange (or about 3-4 mm).
- Fill the catheter and attached flow moderator using a syringe. Leave
the syringe attached to the distal part of the catheter.
- Fill the ALZET pump (see method).
- 200 µl & 2 ml Models: Insert the flow
moderator into the pump until the white flange is flush with the surface
of the pump. The syringe attached to the distal end of the catheter
can now be removed.
100 µl Models: Insert the flow moderator into the pump until the catheter tubing is flush with the surface of the pump. The syringe attached to the distal end of the catheter can now be removed.
- Prime the pumps in sterile saline (see method).
100 µl and 200 µl pumps before and after the attachment of catheters
Impact on Release Rate
The correct use of a catheter with an ALZET pump does not change the release rate of the pump. However, there are situations involving the use of a catheter which can affect the rate at which drug solution is released from the end of the catheter:
- Leakage at the point where the catheter tubing and pump flow moderator connect will decrease the flow along the tubing. If the tubing is stretched during its connection to the flow moderator, a tight fit may not result. Check for leakage at this connection before implantation.
- Diffusion across the walls of the catheter tubing may result in a different concentration of drug at the end of the catheter. Though researchers have successfully used Silastic® tubing for catheter applications with ALZET pumps, it has been noted that Silastic tubing allows diffusional exchange of materials (including water) along the length of the catheter.
- Perforations in the catheter will decrease the flow to the end of the catheter.
Types of tubing which have been used with the pump include:
Available from DURECT Corporation, is suitable for most catheter applications including intravenous and intra-arterial administration. Polyethylene is thermoformable and can be shaped into a coil or drawn down to a narrower diameter over a flame.
Available from DURECT Corporation, does not kink, crimp, or slip off of the flow moderator as easily as some other materials. This material has been used successfully in long-term studies without slipping off, and is also more flexible than polyethylene tubing, bending around corners and sharp angles without serious distortion. Vinyl tubing is recommended for use in brain infusions that require a connection between the osmotic pump and a steel cannula fixed on the skull. Unfortunately, vinyl tubing has not proven to be satisfactory for intravenous use: it can cause a clot to form at the site of insertion into the vessel.
of a fine gauge (such as 32-gauge)
may be more desirable to use in some intrathecal and epidural applications. Some studies have shown it to cause less subclinical damage than other types of tubing. Such tubing is roughly equivalent in size to PE 10 tubing.
If examined under a microscope, “sweats” when filled with an aqueous solution and exposed to air. Indeed, the diffusion coefficients for water and many gases are higher for Silastic than for most other plastics commonly used as tubing. Considering that the volume flow from the pumps is very low, it is undesirable to have diffusional exchange of water through the walls of the tubing at the rates observed with Silastic tubing.
The following sizes of polyethylene (PE) and vinyl (V) catheter tubing fit well onto the flow moderators of all models of ALZET pumps:
|Tubing Type||Inner Diameter||Outer Diameter|
|PE-50|| 0.58 mm
| 0.965 mm
|PE-60|| 0.76 mm
| 1.22 mm
|Vinyl (V/3)|| 0.58 mm
| 0.990 mm
|Vinyl (V/3A)|| 0.69 mm
| 1.14 mm
|Vinyl (V/4)|| 0.76 mm
| 1.22 mm
Polyethylene and vinyl catheter tubing are available in sterile form from DURECT Corporation. Catheter tubing obtained non-sterile may be sterilized in the following manner:
- Polyethylene tubing can be sterilized by gamma irradiation or ethylene oxide (gas sterilization). Do not autoclave.
- Vinyl tubing can be irradiated, gas sterilized, or autoclaved.
- Polyurethane tubing may be gas sterilized. Check the compatibility of chemical sterilizers before using.
pumps are sold in a sterile form. Additional sterilization is discouraged,
since these may interfere with the correct operation of the pumps.
To calculate the volume contained within a given length of tubing, use the following conversions:
|Length of Tubing||Tubing Type||Volume Contained|
|1 cm||PE-60||4.566 μl|
|1 cm||PE-50||2.679 μl|
|1 cm||V3/A||3.739 μl|
|1 cm||PE-10||0.615 μl|
Following are tubing lengths required to hold the entire reservoir volume* of an ALZET pump:
|Pump Volume*||PE-60 Length||PE-50 Length||V3/A Length|
|100 µl||22 cm||37.3 cm||26.74 cm|
|200 µl||43.8 cm||74.7 cm||53.49 cm|
|2000 µl (2 ml)||438 cm||746.5 cm||534.9 cm|
*Based on nominal fill volumes. The exact volume needed depends on the mean fill volume of the specific lot of pumps being used as printed on the instruction sheet supplied in each box of pumps.
These conversions are calculated using the formula for a volume of a cylinder:
πR2 x length = tubing volume
In this equation, R is the radius of a cross-section of the tubing, or half of the inner diameter given in section 3 above. The length is equal to the length of tubing being considered. Be sure to use the same units of measure throughout, and to convert the volume to μl to relate the final volume to the flow rate of the pumps, which is in μl/hr.
Pumps can be used with or without catheters. For catheter applications, the flow moderators supplied with all ALZET pumps will accept any tubing that will grip a No. 21 gauge needle (e.g. PE-60 tubing). If a smaller catheter, such as PE-10 (which grips a 30 gauge needle), is desired, there are two ways of achieving the necessary step-down in catheter size.
Polyethylene tubing can easily be drawn out over a heat source to a very small size. Hold the PE tubing about 6" above a low flame, and rotate the tubing while moving it back and forth across the flame, pulling steadily. After the tubing has been drawn out, attach a water-filled syringe to the unflamed end, using a 21 gauge needle. Apply pressure on the plunger, and using scissors cut off the attenuated end in successive pieces until water flows out. This is the smallest diameter you can reasonably obtain with this procedure.
We have successfully obtained open tips no larger than 4x the diameter of a red blood cell by this means, while the base end of the catheter retained its original geometry to fit on a 21 gauge needle.
Another method for using very
small bore catheters with ALZET pumps is to glue PE-10 tubing inside
PE-60. Be sure to test for leakage at this junction before implanting.
(Sources for purchasing PE-10 tubing)
|Tubing Type||Inner Diameter||Outer Diameter|
|PE-10|| 0.28 mm
| 0.64 mm
Some agents are very expensive or available only in volumes less than 100 µl, which is the reservoir capacity of the smallest ALZET pump. The pump reservoir cannot be filled to less than capacity, since doing so would result in a reservoir filled partially with solution and partially with air, causing discontinuous delivery of the solution. The ALZET pump is easily adapted for delivery of smaller volumes by attaching a small “external reservoir” made of catheter tubing.
For example, to deliver 25 µl of solution, one would fill a short piece of catheter tubing just long enough to hold 25 µl of solution. This tubing would then be attached to an ALZET pump completely filled with a control solution (e.g., saline). In this example, 5.5 cm of PE-60 tubing would be sufficient. Refer to Catheter Volumes above to calculate the length of tubing needed. If the required tubing will be too long and unwieldy for implantation, refer to Preparing a Lynch Coil to make it more space efficient.
If mixing between the control and test solutions is a concern, one of the following may be done:
- Use a control solution which is immiscible with the test solution
- Introduce a small amount of a “spacer” solution (e.g., air or mineral oil) into the catheter tubing where it connects with the pump
The Lynch coil method can be used for several purposes:
- Create a time-patterned delivery of an agent
- Deliver compounds and/or vehicles which are incompatible with the reservoir of the ALZET pump
- Provide an initial period of no drug delivery for surgical recovery
- Provide a short period of drug delivery with a longer duration pump
Polyethylene tubing should be used because it is thermoformable and can be formed into a permanent coil. The length of tubing depends upon the size and duration of pump being used, and the duration of infusion desired from the solution in the coil. The pump itself is filled with saline, which is separated from the drug solution by a drop of mineral oil or other nonmiscible compound or a bubble of air placed in the tubing at the end between the coil and the pump.
To fabricate the Lynch Coil using polyethylene tubing:
- Using closely spaced turns, wind the appropriate length of PE-60 tubing around a glass rod or syringe of the same outside diameter as the ALZET pump.
- Submerge the rod and the tubing in boiling water for one minute.
- Immediately immerse the tubing into ice water for one minute
- Basic method reference: P0065 Lynch et al, Neuroendocrinology 31, 106-111, 1980.
- See Catheter Volumes to determine tubing length.
Lynch coils attached
to ALZET Osmotic Pumps
- Ensure around-the-clock exposure to test agents at predictable levels
- Permit continuous administration of short half-life proteins and peptides
- Provide a convenient method for the chronic dosing of laboratory animals
- Minimize unwanted experimental variables and ensure reproducible, consistent results
- Eliminate the need for nighttime or weekend dosing
- Reduce handling and stress to laboratory animals
- Small enough for use in mice or very young rats
- Allow for targeted delivery of agents to virtually any tissue
- Cost-effective research tool
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“A continuous infusion paradigm was utilized in both experiments to minimize any potential hemodynamic side effects from bolus NTG administration... Cha et al., Pharm Bioch and Behav 2003;74:551-557.