Single-use equipment already plays an integral role in many bioprocesses. For example, disposable bag systems serve for storage, transportation and mixing. Single-use bioreactors are increasing in capacity and complexity and come supplied with single-use coupling and sampling components. Disposable equipment also can handle formulation, filtration and filling.
Manufacturers gain obvious benefits in terms of cost, cleanliness, validation and speed, but these shouldn't come at the expense of process performance. Optimal processing demands non-invasive single-use sensors to monitor parameters such as flow, pressure, pH, dissolved oxygen, conductivity and turbidity. So, suppliers are working hard to develop and enhance measurement technologies.
"What we are seeing is that the more heavily regulated processes are moving to single-use technology as a means to improve process efficiency, flexibility and conserve resources. It is common to eliminate hours or even days of production downtime while process piping and equipment is cleaned, sanitized and validated between production runs or changes in formulation. The potential annual cost savings from no longer needing clean water treatment for steam cleaning or wastewater treatment for the residue from cleaning can also add up to thousands of dollars. So engineers and scientists that work with these processes are pressing for accurate and reliable single-use sensors," says Curt Pinnow, new product development manager at fluid-handling specialist Cole-Parmer, Vernon Hills, Ill. He adds that units for pressure, conductivity, temperature and flow are the most common disposable sensors.
"Some of this need is simply the desire to have 100% of the process be single-use. However, another need is to be able to make a complete process sub-assembly portable. An example would be a tangential flow filtration (TFF) assembly (Figure 1), or a depth filtration skid," he adds. Bioreactor monitoring and filter screening sub-assemblies also are seeing increasing demand.
"One feature of the movement to single-use systems is the desire of the end-user to have a completely closed/sealed system, with no intrusions that may possibly damage or contaminate the contained biofluid. This has led to the development of non-contact/non-invasive sensors to measure attributes such as dissolved oxygen. While I don't know if these sensors are classified as disposable, the intent and usage is the same," notes Pinnow.
So for marketing purposes, Cole-Parmer combines these non-invasive sensors with disposable sensors into a new product category that allows users to address traditional measurement in new and innovative ways.
"The takeaway here is that the sensor manufacturers have managed to develop the technology in products priced so that they are truly single-use," he concludes.
STRONG INCENTIVE
"The interest in single-use/disposable systems has really taken off within the last ten years. In a nutshell, the cleaning/validation cycle of traditional stainless steel equipment takes time and requires a lot of high-cost, hard-plumbed steel equipment, as well as pure water and steam generation with associated energy costs, and waste disposal. Single-use systems enable a quick turnaround, lower investment, and minimization of errors during this cycle," says Dennis Annarelli, technical manager of sensor-maker PendoTECH, Princeton, N.J.
The company's oldest product line, first marketed in 2006, consists of single-use pressure sensors. "The sales line has increased year-on-year since then. The need to measure pressure is ubiquitous in bioprocessing," notes Annarelli. Applications include multi-stage depth filtration, TFF/crossflow filtration and bioreactor pressure monitoring.
PendoTECH's second single-use sensor, launched within the last year, is a temperature sensor that reportedly is attracting a lot of attention from bioprocessors.
The company already offers single-use rotary flow meters and non-disposable Coriolis flow meters, but now is developing a single-use Coriolis flow meter that it hopes to have on the market by the end of the year. "There is a lot of demand from biopharma companies for mass flow measurement, not least because there is a lot of viscosity change to products during purification processes, which does not impact the Coriolis measurement. The ability to measure at low flows is also very important: the Coriolis flow meter is accurate down to a few mL/min — making it ideal for lab-scale trials," explains Annarelli.
The firm's new single-use inline flow-through UV absorbance cell for chromatography is generating a lot of interest, he says. In bioprocess operations the UV absorbance of a liquid solution can identify the absence or presence of a molecule of interest. The measurement, typically at 280 nm, is made by a spectrophotometer. An inline cell allows for real-time process decisions.
"We also have an inline turbidity cell, which is not strictly single use, but priced ($150) in a way that it could be used as such. Turbidity is important in filtration processes: when filters start to plug, particles can sometimes pass through even before pressure builds up on the filter. A turbidity cell can detect this. It can also be important in initial centrifugation stages: if solids are passing on from this stage, the centrifugation process is not optimized," adds Annarelli.
In addition, the company is grooming a single-use conductivity cell, which should be ready by the end of the year.
"We see even bigger opportunities in the future as the industry moves towards smaller-scale, individually tailored medicines… This is also being reinforced by governments' demands that drug companies show that their products really do work by requiring more diagnostic testing, etc., before therapies are approved."
The company wants to be a full-service supplier of single-use sensing technology to the biopharma industry. "We find partners who have sensing technologies that we can take to our own industry. Right now, however, single-use pH sensing over a wide range of pHs is something we simply cannot do," Annarelli notes.
MULTIVARIABLE SENSING
GE currently is focusing much of its effort on developing passive multivariable radiofrequency identification (RFID) sensors (Figure 2) for single-use biopharmaceutical manufacturing components such as buffer bags, connectors and bioreactors, says Radislav A. Potyrailo, principal scientist, chemistry and chemical engineering, at the company's Global Research Center, Niskayuna, N.Y.
"Typical existing sensors have one output per sensor, but if there are other parameters that affect the same sensor you are unable to find out exactly what is going on. Having several outputs, multivariable sensors can avoid this," he explains.
Portyrailo and his colleagues have been working on a technique that does away with costly proprietary RFID memory chips and their analog inputs in favor of passive 13.56-MHz RFID tags. These operate as inductively coupled sensors with 16-bit resolution provided by a sensor reader. "We have developed RFID sensors for the measurements of several critical manufacturing parameters such as pH, solution conductivity, temperature and pressure," he notes.
In over 500 hours of laboratory tests, the sensors have proven extremely accurate, both individually and when tested in different combinations.
The development process received a major boost in late January with the announcement of a partnership with Avery Dennison, Pasadena, Calif., to commercialize the RFID sensor technology.
"The goal of our partnership is to point these wireless RFID sensors to a series of applications ranging from food and beverage, to packaging, pollution prevention and industrial. While the full specification sheets for desired sensors in these and other applications are surely quite diverse, there are several common key requirements that are unmet by existing available sensors. These requirements include (1) high selectivity of measurements of chemicals of interest in the presence of high levels of interferences, and (2) achieving this selectivity without costly investments into electronic nose systems that are expensive, being $4,000–$50,000," explains Potyrailo.
COMBINED SENSOR
Finesse Solutions, San Jose, Calif., chose Interphex 2011 in March in New York City to give bioprocessing companies a close-up look at its new single-use SensorPak. Integrated with its SmartBags plug-and-play bioprocessing containers, the sensors reportedly provide accurate, drift-free, in-situ pH and dissolved oxygen (DO) measurements for at least 21 days.
The SmartBag SensorPak leverages the company's TruFluor pH and DO phase fluorometric technology in a compact pre-calibrated assembly. The combined pH and DO optical reader uses advanced optical components including a large area photodiode that minimizes photo-degradation of the active sensing elements.
"This product is optimized for accuracy, lifetime, and ease of use. We anticipate that the SensorPak will provide a complete solution for single-use seed train bio-processing applications, which are still in great need of reliable and trustworthy key process parameter measurements," notes Mark Selker, the firm's chief technology officer.
The company also has released its T700 upstream processing platform for single-use bioreactors ranging from 25 L to 2000 L in size. Each turnkey system comprises TruViu G3 hardware, TruBio software, and TruFluor/TruTorr single-use sensors. The T700 platform brings the benefits of Emerson Process Management's DeltaV reliability for cGMP applications in an affordable package, with easy scalability to multiple process trains using the DeltaV TruLogic Controller, claims Finesse.
"We have worked closely with our end users to define the requirements for the next-generation single-use bioreactor controller. Seamless integration of single-use sensors and sensor redundancy were two key challenges to resolve. Our T700 platform allows end users to seamlessly transition from traditional to fully redundant single-use sensors. This represents a major advance in the control of single-use bioreactors," says John Greenwood, manager of integration and automation.
Finesse also has launched the core module of its VirtualTransmitter for interfacing to TruFluor pH and DO single-use sensors. "As single-use sensors become the de facto standard in bioprocessing, end users will expect them to be perfectly integrated into both the hardware and software of the control platform. VirtualTransmitter and TruFluor blades represent the next-generation evolution of our single-use bioreactor control product line," states CEO Barbara Paldus.
NEW PLATFORMS
Meanwhile, SciLog of Madison, Wis., a developer of single-use sensors to measure conductivity, pressure and temperature, now is incorporating its sensors into disposable purification platforms — for TFF, normal flow filtration and chromatography.
Such platforms typically consist of an integrated assembly of filter elements or columns, flexible tubing, plastic connectors and bags, segments of peristaltic pump tubing, as well as sensors. They are designed and pre-assembled for a specific purification process and a given maximum process volume. In the final configuration, all elements of the purification platform are pre-sterilized, assembled and operated as a closed system.
SciLog's latest offering is the SciPure 200 automated single-use TFF system. Designed to meet cGMP and 21 CFR Part 11 standards for data-collection and security as a standalone device, the system is ideal for product development, process development and biomanufacturing, claims the company. Users can create and execute discrete or batch operations for filling, concentration and filtration via a color HMI touch screen and pre-installed software. All wetted flow-path manifold components are considered single-use consumables.
SciLog hopes to launch a range of sensors to measure parameters other than conductivity, pressure and temperature later in the year.
Seán Ottewell is Chemical Processing's Editor at Large. You can e-mail him at [email protected].
