RTubeVENT™ Breath Condensate Collection Device

Overview

Exhaled Breath Condensate Collection from Intubated and Mechanically-Ventilated Patients in the ICU

The RTubeVENT™ breath condensate collection device is designed for ease of use in the ICU. It can be placed in-line in the expiratory limb of the breathing circuit or at the ventilator exhaust port. This non-invasive handheld device is fully self-contained and disposable. As the subject is ventilated, the RTubeVENT gathers breath condensate in a special cartridge designed exclusively for ventilator use.

• Single use disposable device for research-only use on mechanically ventilated patients
• Optimized for ventilator use either inline or on ventilator exhaust port
• Provides a safe, simple way to collect exhaled biomarkers in ventilator applications

Cooling Sleeve

The cooling sleeve is necessary for efficient condensate collection. Usually stored in a laboratory freezer until needed, the sleeve is designed to easily slide over the RTube and create the perfect environment for condensate collection. An Insulating Cover is included with every Cooling Sleeve.

Our high quality cooling sleeves are cold-worked from solid aluminum and have been designed for repeated use under the harshest freeze/thaw conditions.

RTubeVENT Collector and Accessories

The RTube is designed as a disposable, single use item. The cooling sleeve, the insulating cover and the plungers are fully reusable. A key feature is the ability to collect the condensate sample, store the sample, transport the sample, and analyze the sample all in the same RTubeVENT. No transfer of condensate fluid into another device is generally required, minimizing complexity in the lab and at the patient’s home. Opportunities for contamination are virtually eliminated and labor required for sample processing is minimized. Every step has been painstakingly thought out and this design created to minimize the effort and complexity for the patient, researcher, and lab technician. The system is designed for ease of use even in very large clinical studies.

Typical condensate fluid yield is 100 microliters per minute. A15-minute collection time is commonly employed so that extra sample might be frozen for other investigations.

Step 1: Condense Exhaled Breath using the RTubeVENT.
Step 2: Store/Transport Condensate
Step 3: Use the Plunger to Collect EBC into a Pool at the Top of the RTubeVENT
Step 4: Analyze the Sample

Step 1: Condense Exhaled Breath Using the RTubeVENT

1-1 Prepare the cooling sleeve before taking samples:

• Place the aluminum sleeve into a plastic bag to prevent moisture from freezing to the inside of the sleeve and contaminating the sample.
• Place the sleeve into a freezer of the appropriate temperature, depending on the exhaled substance of interest. Home freezers work well for stable compounds.
• Allow the sleeve to cool to the appropriate temperature. While transporting the sleeve over long distances, store in an ice chest filled with ice or frozen packets.

1-2 Prepare the RTubeVENT: The RTubeVENTs are sent ready to use for most applications; however, when studying compounds in EBC that are found diffusely in the laboratory setting as contaminants, extra precautions should be taken. These include, but are not limited to, nitrate and nitrite. We recommend that you wash the condensing chamber with ultrapure deionized water which meets or exceeds specification ASTM D 1193 for Type I and type II Reagent Grade Water and allow them to dry fully before use to eliminate any possible contamination.

Also, the RTubeVENT is designed to mate with a 22 mm Male tapered connector on both ends. This will typically require a 22mm Male X 22 mm Male adapter be used at one end if placed inline in a standard breathing circuit.

1-3 Fill out label on RTubeVENT and note whether the collection is occurring in the expiratory limb or ventilator exhaust. The location of the collector can influence the biomarker content of the condensate.

1-4 Place the blue insulating cover over the aluminum cooling sleeve to protect your hand and keep the aluminum cold.

1-5 Place the aluminum sleeve over the outside of the RTubeVENT and position in the exhalation path as desired. Options include inline positioning in the exhalation limb and placement at the ventilator exhaust.

1-6 Collection times should be standardized for each application. We recommend a fifteen-minute collection time for most applications.

1-7 After sample collection has been completed, remove the RTubeVENT from the exhalate path, slide the cooling sleeve off. You may observe a tiny amount of sample loss during this process. This is normal. Place the cooling sleeve back into the protective bag and refreeze.

Step 2: Store/Transport Condensate

2-1 Cap both ends of the RTubeVENT.

Freeze the sample at the appropriate temperature or leave at room temperature if appropriate for the compounds of interest. When studying stable compounds a sample can be stored at room temperature or in a home/laboratory freezer until needed. If packaged properly and kept out of high heat, the sample can be shipped by mail with no contamination or loss of sample fluid. When studying common laboratory contaminates the sample should be removed from the collector and stored in the freezer as soon as possible.

Step 3: Use the Plunger to Collect EBC into a Pool at the Top of the RTubeVENT

3-1 In the laboratory, remove the cap and place the RTubeVENT over the top of Standard Plunger and push down until the RTubeVENT touches the base of the Standard Plunger. As the RTubeVENT is pushed down over the Plunger the nose on the end of the Plunger engages the lower piston and strokes it the entire length of the condensation surface much like a syringe. The result is a neatly presented .5 ml – 1.5 ml pool of pure EBC ready for analysis.

Step 4: Analyze the Sample

4-1 This step is of course dependent on the substance of interest. The substance my be unstable, and require rapid analysis, or it may be very stable (as is the case for pH) and be analyzed anytime.

The RTubeVENT is designed as a disposable, single use item. The cooling sleeve, the insulating cover and the plungers are fully reusable.

A key feature is the ability to collect the condensate sample, store the sample, transport the sample, and analyze the sample all in the same RTube. No transfer of condensate fluid into another device is generally required, minimizing complexity in the lab and at the patient’s home. Opportunities for contamination are virtually eliminated and labor required for sample processing is minimized. Every step has been painstakingly thought out and this design created to minimize the effort and complexity for the patient, researcher, and lab technician. The system is designed for ease of use even in very large clinical studies.

Regulatory

USA: FDA Regulatory Status of the RTube family of products

RTube is registered with the United States Food and Drug Administration as a Class I device for Research Use Only. You may see our device registration at:

https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfRL/rl.cfm?lid=198613&lpcd=KGK

As such all use of the RTube must be conducted under the supervision of an Investigational Review Board (IRB), which is common to almost all human studies, and no therapeutic or medical decisions may be based on the outcome of analyses using the RTube collector.

Europe: The RTube falls outside the EU IVD Directive and requires no CE mark

The RTube Exhaled Breath Condensate Collector is clearly and permanently labelled “For Research Use Only” on the device itself, is not an In-Vitro diagnostic (IVD), and therefore falls outside the EU IVD Directive and requires no CE mark.  As such all use of the RTube must be conducted under the supervision of an Investigational Review Board (IRB), which is common to almost all human studies, and no therapeutic or medical decisions may be based on the outcome of analyses using the RTube collector.

Please see references below:

Recital 8 of the IVD Directive 98/79/EC states: “Whereas instruments, apparatus, appliances, materials or other articles, including software, which are intended to be used for research purposes, without any medical objective, are not regarded as devices for performance evaluation.”

Further based on guidance document MEDDEV. 2.14/2 rev.1 Section 5 (a):

5. Potential Situations where “RUO” Labeled Products could be used

The following are a list of possible situations where RUO products could be used and which therefore fall outside the scope of the IVD Directive.

(a) RUO products used for Basic Research:

These are products used for research conducted to study all aspects of human life in an attempt to better understand all underlying mechanisms. In such studies / experiments animal and / or human models are used. No medical purpose is defined, as the specimens taken are not being used for the purpose identified in the definition of an IVD device in the IVD Directive, article 1 2(b). In such practice there is no potential to misuse RUO products.

Institutional Review Board/ Human Investigation Committee Consideration of the RTube family of products

Over 230,000 samples have been collected from ambulatory subjects worldwide with the RTube over the last 25 years with zero adverse events attributed to its use. Our device and methods have been considered non-significant risk by multiple Institutional Review Boards. Each individual Institutional Review Board/ Human Investigation Committee may wish to make its own determination as to the non-significant risk nature of the device, especially if the device is modified or incorporated into other equipment.

Technical Information

How it Works

The RTubeVENT is a simple device which utilizes two sealing pistons to create an annular space within a tube. As air passes through the device, the chilled walls of the tube condense the exhalate into a condensate film. This film clings to the walls until wiped by the sealing piston as it is pushed along the tube much like a syringe. The condensate becomes trapped in the annulus created by the extended piston skirt and the tube wall.

Turbulence is created by the nozzle as the air jet spreads out into the cylindrical condensation chamber. The effect is easy to test: during use place your hand above the top of the RTubeVENT as you exhale. Your exhaled breath will feel cool. Remove the pistons, re-freeze the cooling sleeve, and try again. This time your breath will feel warm even though you are using a fully-chilled cooling sleeve. The difference is the absence of turbulence normally created by the pistons. Warm exhaled breath means lower heat transfer, less condesation, and therefore less sample yield. While many homebuilt devices can be found in the literature, none of them will yeild the efficiency of time and quality of sample you will get with the RTubeVENT.

Quality

Our commitment to quality extends far beyond our product. At Respiratory Research, Inc., it is a way of business. We require that leading industry quality practices be applied to all products and processes. This includes Supplier Qualifications, Engineering, Procurement, Manufacturing, Order Fulfillment, and Technical Support.

We work with ISO 9000-certified suppliers only. Top-tier suppliers are provided current engineering documentation at all times and apply their own internal quality systems to ensure that all products supplied to Respiratory Research, Inc. are in full conformance with these engineering specifications. Respiratory Research, Inc. thoroughly and completely documents all product requirements using engineering drawings bills of material, assembly procedures, environmental specifications, and component specifications. These are maintained by Respiratory Research, Inc. and are under full revision control.

RTubeVENT Materials and Performance

The RtubeVENT Exhaled Breath Condensate Collector is specifically designed to meet the needs of a wide range of subjects, investigators, and clinicians. Its size, weight, materials, and performance characteristics have been carefully selected to provide the maximum safety, effectiveness, and flexibility.

Example of RTubeVENT Flow Charcteristics

• Example Test performed at Exhaled Breath Research Lab, Virginia Commonwealth University School of Nursing, using a Puritan Bennet 840
• Ventilator Self-Test sequence run with standard circuit
• Ventilator Self-Test run again with RTubeVENT in exhalation limb of circuit
• Both test series passed
• Conclusion: Ventilator functions normally with the RTubeVENT in the breathing circuit

Testing performed by the Breath Lab at Virginia Commonwealth University School of Nursing.

Cautions and warnings

A WARNING, if unheeded, could potentially affect the patient.

A CAUTION, if unheeded, could potentially affect the quality of the sample or present a hazard to the medical and laboratory staff.

For safety the RTubeVENT has no internal restrictions or blockages. It can be oriented in any direction and placed in circuit with either end facing the patient. It is designed to mate firmly with standard breathing circuits incorporating 22 mm Male connections. However, these are not locking connections and it is possible that the RTubeVENT can become disconnected from the breathing circuit while in use. Patient movement, improper installation of the RTubeVENT in the breathing circuit, or exceptionally-high PEEP settings may cause the RTubeVENT connections to the breathing circuit to open. While it is likely that the ventilator will sense this break in the circuit and sound an alarm, the complete dependence upon external intervention requires strict supervision of the patient and proper precautions.

The cooling sleeve must never be allowed to lay on the unconscious patient, especially bare skin. This is to prevent any possible injury due freezing of skin. The insulating cover is only for handling convenience and will not protect the patient from an exceptionally-cold sleeve. Be sure to properly support the breathing circuit away from the patient and monitor the position of the cooling sleeve at all times while it is in the circuit.

The RTubeVENT is a disposable device designed for single use. It is assembled to stringent specifications and cleaned under strictly controlled clean-room conditions to ensure proper operation, safety, and cleanliness. Any subsequent rebuilding or tampering with the device will reduce the effectiveness of the device, risk the quality of your data, and potentially pose a safety risk to the patient.

The RTubeVENT cartridge is supplied with two end-caps which should be placed on the ends. Once the caps are properly attached, the EBC sample will be trapped inside of the collection chamber and can be stored and transported as needed. Failure to cap the ends of the cartridge will result in sample loss and/or contamination during transport.

Prior to thawing a frozen condensate specimen, be sure to remove a cap from either end of the RTubeVENT to prevent cap pop-off. This occurs due to the pressure increase from expansion of the air and vapors inside the cartridge as the temperature is normalized to ambient. This pressure buildup can pop off caps with enough force to become airborne and sample loss may occur.

For best sample retention during thawing, orient the RTubeVENT at a 30-degree to 60 degree angle from vertical. This will allow the specimen, which may have frozen in unpredictable places inside the capped tube, to re-collect in the proper spaces around the pistons.

Please contact RRI for more information regarding the safe and effective thawing practices.

Nitric oxide can diffuse through various materials, and its oxides, including nitrite and nitrate, are common and abundant contaminants on laboratory surfaces.

If nitrogen oxides are to be assayed we strongly recommend rinsing with deionized water all apparatus that will come in contact with the exhaled breath condensate sample as close as possible to the time of use. This includes the inside of the RTube condensing chamber, microcentrifuge tubes, and pipette tips. Note that many latex gloves are highly contaminated with nitrogen oxides. We recommend plunging and removing sample from the RTube within 24 hours if nitrogen oxides are of interest. Additionally, we recommend analyzing the sample as soon as possible if nitrite is of interest.

The RTubeVENT is an investigational device only and is designed for research purposes. Due to the non-invasive nature of the device, the RTubeVENT is exempt from the Investigational Device Exemption of the United States Food and Drug Administration. Any invasive use of the device or use outside of protocols approved by local Institutional Review Boards is not supported by Respiratory Research, Inc.

The RTubeVENT should be handled with a slow, steady, controlled motion when inserting onto plunger. This steady motion should be maintained even if unpredictable resistance levels are met. If excessive force is used and the resistance unexpectedly drops, the rapid motion of the RTubeVENT as it is forced over the plunger can distort the internal parts and can result in partial loss of sample