Cold comfort

Carbon dioxide is a liquefied gas refined, and sourced from a handful of chemical, energy, and natural sources. The sources are primarily from fermentation by-product in industrial ethanol production, a by-product of anhydrous ammonia production, and reformer off-gas in refineries. CO2 is also sourced from naturally occurring geologic domes. A few other source types exist, such as flue gas from cogeneration, titanium dioxide and ethylene oxide production.

Of the total merchant market usage, about 70 percent is dedicated to food and beverage production, followed by an industrial sector, including natural gas well fracturing, pH reduction, uranium leaching, insect control, dry ice production, and many more applications. Finally we consider US Pharmacopeia (USP) grade CO2, a small, volume-driven business, catering to the medical trade specifically. This represents less than two percent of the overall US CO2 business.

USP grade CO2 originates, on a producer’s level, from the majors such as Linde. These major CO2 producers have strategically located plants which produce a CO2 grade for USP service. In the case of Linde in the United States, its plants in Fulton, NY, Lima, OH, and Torrance, CA produce USP grade CO2 - the other majors have generally two or three plants which yield a USP grade CO2 domestically. This is one of two specific grades or specific definitions for CO2 produced for industry at large. Another grade is defined by the International Society of Beverage Technologists (ISBT). This meets the needs of soft drink and beverage grade products. One reason why beverage grade has such a strict definition is due to numerous accidents where contaminants were contained in a refined product, which then went to the beverage markets resulting in an off-taste product.

USP sets standards for the quality, purity, strength, and consistency of products critical to public health. USP’s standards are recognized and used in more than 130 countries worldwide. USP CO2 is also known as medical carbon dioxide. A USP grade product is relatively expensive on the markets, compared with merchant product sold, largely due to a high cost of documentation surrounding the assay, quality, and production of the product; as well as costs associated with regulatory compliance and the cost of audits. The USP purity assay calls for CO2 to be not less than 99.0 percent by volume. The gas is described as odorless, colorless, with a solution acidic to litmus. It calls for further tests and limitations of impurities including H2O, CO, H2S, NO, NO2, NH3 and SO2. The USP gas is a respiratory stimulant and it has applications by inhalation, using up to seven percent in oxygen.

Surgical uses
In general, many USP producers and providers term the grade as ‘medical carbon dioxide’ quite commonly. With respect to a wide range of medical purposes, beyond respiratory stimulation, numerous interesting cases exist. This grade has applications as an insufflation gas for minimally invasive surgery (i.e. arthroscopy, laparoscopy, and endoscopy) intended to enlarge or stabilize body cavities for improved visibility and access with surgical instruments during surgery. Users also employ the gas as a temperature reduction agent, down to -76° C (32° F). Medical grade carbon dioxide is used for cryotherapy and for local analgesia by external application on the skin surface. A further application creates a state close to physiological atmosphere when USP CO2 is mixed with medical oxygen to operate artificial organ systems such as a kidney dialyzer, and pump oxygenator; again for injection into body cavities during surgical procedures.

Beyond cryosurgery, cryopreservation includes biological materials from cells, tissues, and gametes, to embryos both animal and human for long-term preservation. Scientists often add specific substances to the tissue samples to protect the cells during freezing and thawing. When considering a hypothermic condition with CO2, this involves temperatures less than normal metabolic readings, suitable for tissue transplant. CO2 of a non-medical nature such as dry ice can be used to transport these tissues to a surgical environment, to preserve and handle tissue samples and for longer-distance transportation. Specific applications with USP grade CO2 can occur for lyophilisation (or freezer drying processes), used in pharmaceutical production, which are of a USP nature. This has created further niche markets in specific pharmaceutical settings.

The cryogenic freezers that we use to preserve tissue samples and similar medical and pharmaceutical materials may not require a medical grade CO2, unless otherwise specified. However, in broad terms, this is actually a medical or pharmaceutical application. Where CO2 does not directly touch live tissue materials, USP grade is not generally used, however a standard merchant grade product usually produced in a plant which would yield an ISBT or beverage grade product as the main so-called grade is typically selected.

Cold cure
As well as liquid nitrogen, physicians also use medical grade CO2 to treat skin anomalies such as keratosis and skin cancers by freezing. The aim is to remove abnormal cells and prevent their spread to surrounding tissue, although this treatment cannot cure diseases such as malignant melanoma per se. It is used frequently for other surface skin treatments such as removing viral warts or non-malignant moles as well.

Another growing area for CO2 is for skin rejuvenation and aesthetics. Dermatologists now turn to CO2 and erbium laser for skin resurfacing, which has demonstrated great success in the removal of sun-damaged skin, eye wrinkles, and smokers’ lip lines, among other cosmetic challenges. The treatment works by vaporizing a layer of surface skin cells, and by stimulating collagen production.

So as a general rule, USP grade CO2 is the norm for removing tissue through freezing. Where there is no direct contact with the sample or tissue, a non-medical grade will suffice for freezing. The aim is to balance stopping biological activity through freezing with minimal damage to cells during the freezing process. Without the use of cryoprotectant solutions there is a risk of preserved cells being damaged due to freezing during the approach to low temperatures or warming to room temperature. Rapid cryogenic freezing results in less tissue damage - fewer sharp ice crystals are formed during the freezing process, which helps to preserve the cellular walls. Leakage of cellular fluids is also minimized via cryogenic freezing.

Finally on the far frontiers of cryogenics lie those who operate cryonics labs, which freeze human body parts or a beloved family pet. However the whole cryonics lab preservation concept is arguably flawed due to ethical considerations: cryopreservation of people or large animals is not reversible with current technology. The technique banks on some future advanced technology becoming available and on a number of unproven assumptions.

By contrast, cryobiology, cryopreservation and cryosurgery are all real-world, legitimate sciences which employ CO2, and sometimes medical grade (or once again USP grade) CO2 in the service of medicine. From the early days of carbon dioxide’s simple application for respiratory stimulation, applications for this USP gas have grown - a trend which looks set to continue as we continue to push back the frontiers of biology and use increasingly sophisticated medical solutions.

Making the grade
A note about grades - there can be a broad industrial grade CO2, if sold strictly for oil and gas applications, or specific niche requirements, such as to manufacture urea. On the other hand, an application in the Green River Wyoming area is the production of sodium bicarbonate. Some of this is used in food related applications (ingestion and topical usage), and so the CO2 feedstock here would meet ‘food grade’ standards. Generally speaking, most merchant plants produce a single grade for one and all, unless it is dedicated to providing industrial grade CO2; or is one of a handful of plants strategically located by a gas firm producing a USP grade.

When dry ice is used for temperature reduction applications, such as refrigerating tissue samples, or for transporting transplant tissue/organ materials from a donor to a patient, this is not considered as a medical grade carbon dioxide product. Dry ice is also used to cool alcohol solutions in organ and tissue chilling applications.