Tower_Circle Image

Inhalation Research

Inhalation Dosing Towers ensure that simultaneous exposure of compounds or gases to the lungs of rodents is well controlled, consistent, and defined. It is crucial that researchers calculate an accurate measurement of the inhaled drug, which is derived by knowing the concentration of the drug delivered as well as the animal’s minute volume.  Most systems use an assumed minute volume value based on animal species and mass; DSI’s inhalation tower provides the ability to integrate plethysmography, allowing for direct minute volume measurement, eliminating the need to make assumptions.

Inhalation towers are used in a variety of research disciplines.

  • Inhalation toxicology - study pharmaceuticals, chemicals, and animal health
  • Biodefense Aerobiology - Infections disease, vaccines, and anti-terrorism research
  • Pharmaceutical and contract research organizations – assess the impact of a compound on major organ systems or evaluate the safety of new drug candidates
  • Discovery and Academic – focus on studies for the proper treatment of respiratory diseases
  • Environmental Toxicology – evaluate respiratory health hazard of airborne particulates

The 14-port inhalation tower uses a flow-past design in which there is an inner and outer column.  The aerosol or gas is introduced into the inner column and drawn out from the outer column. The subjects are typically arranged as spokes around the tower where they receive air to breathe from the inner column, while the outer column draws away the excess.  Each subject has its own port and care is taken to ensure that each port is identical in every way.   Symmetry of design is critical.  

Controlling the exposure is the job of the All-In-One Tower Controller.  The tower controller uses two mass flow sensors to monitor and regulate two flows.  One flow provides air into the tower, and the other flow draws air out of the tower.  The unit regulates the pressure in the outer column to achieve a target pressure which is either slightly above or below zero, as selected by the user.  This pressure is monitored in real time, providing instant feedback and uses rapid response valves to allow the excess pressure to vent as needed.

In addition to providing flow and pressure regulation, the tower controller also provides ports for:

  • Two photometers so that aerosol concentration can be monitored in two locations
  • One external Temperature & Humidity sensor
  • One Aerosol Nebulizer head
  • 4 Flow transducer ports so that ventilation of up to 4 subjects can be monitored during exposure

 

The following parameters are reported from the tower controller (exposure portion):

Parameter

Description

Units

Concin

Concentration from the photometer placed near the inner column

mg/m3

Concport

Concentration from the photometer placed at a port

mg/m3

P

Pressure in the outer core

cmH2O

Tin

Temperature measured as the flow exits the Tower Controller

C

Hin

Humidity measured as the flow exits the Tower Controller

%

Tport

Temperature measured at the port

C

Hport

Humidity measure at the port

%

Fin

Mass flow rate of air entering the tower (exiting the Flow-Balancing unit)

L/min

Fout

Mass flow rate of air exiting the tower (not counting the overflow)

L/min

Pbaro

Current barometric pressure

mBar

 

Using FinePointe software and optional plethysmographs, common pulmonary parameters can be derived from a respiratory flow signal:

 

Parameter

Term

Units

Description

f

Frequency

BPM

The instantaneous, breath-by-breath rate of breathing

TV

Tidal Volume

mL or L

The inspired volume of air per breath. The integral of the negative section of the flow curve

MV

Minute Volume

mL/min or L/min

The product of the tidal volume and the respiratory rate, calculated on a breath-by-breath basis

AV

Accumulated Volume

mL or L

Total volume breathed over a specific period of time. Calculated by adding the TV for each breath to the previous Accumulated Volume. Used in Dosimetry experiments, AV provides a good measure of the actual dose an animal receives.

PIF

Peak Inspiratory Flow

mL/sec or L/sec

The maximum inspiratory flow that occurs in one breath

PEF

Peak Expiratory Flow

mL/sec or L/sec

The maximum expiratory flow that occurs in one breath

Ti

Inspiratory Time

Sec

The time spent inhaling during each breath, from the start of inspiration to the end of inspiration (determined by interpolation of start of expiration). The time flow is negative

Te

Expiratory Time

Sec

The time spent exhaling during each breath, from start of expiration to end of expiration (determined by interpolation back to zero). The time flow is positive

dV

Delta Volume

mL or L

The difference between inspiratory and expiratory volume

EF50

The flow at the point 50% of TV is expired

mL/sec or L/min

An indicator of bronchoconstriction

Tr

Relaxation Time

Sec

The time it takes for the animal to expire a certain amount of volume

Rinx

Rejection Index

%

Calculates the percentage of breaths rejected

  • All-in-one Tower Controller
  • 14-port Inhalation Tower (aluminum or stainless steel)
  • Aerosol block with nebulizer head
  • Driers and Filters
  • Patented Allay animal restrainers and optional plethysmographs
  • Support pins for securing heavier animals
  • Optional photometer(s)
  • 4 Flow transducers
  • One calibrator column
  • One optional temperature and humidity sensor
Inhalation Tower Solution with Tubing

All-in-one Tower Controller and 14-port inhalation tower.


Inhalation Tower with Allay Restraints - Mouse

Inhalation tower with Allay restraints (mouse version shown).

Sodium colistimethate loaded lipid nanocarriers for the treatment of Pseudomonas aeruginosa infections associated with cystic fibrosis. Pastor M, Moreno-Sastre M, Esquisabel A, Sans E, Viñas M, Bachiller D, Asensio V, Del Pozo A, Gainza E, Pedraz J. International Journal of Pharmaceutics. 2014; 447: 485-494.

A Miniaturized Inhalation Tower to Deliver Small Amounts of API to Conscious RatsAileen House, Walter Horodnik, Jennifer Wilson Wylie, UV Shemesh, Joe Lomask, Ester Carballo-Jane and Peter J. Mauser. Merck Research Laboratories, Kenilworth, NJ, Merck Respiratory Product Development, Summit NJ and Buxco Research Systems, Wilmington, NC, USA.


Use of the Allay Restraint Collar to Facilitate the Measurement of Ventilation in Conscious Rats
Richard William Chapman, PhD