- Cool Tool – Online Cell Culture Media Formulation ToolPosted 3 days ago
- Video – Impact of Chemically Defined Media on Product QualityPosted 4 days ago
- Ask the Expert – Media Optimization Can Improve Glycosylation Patterns and Consistency to Impact Protein EfficacyPosted 5 days ago
- Digital Biomanufacturing Will Enable Tissue BioprintingPosted 2 weeks ago
- Video – When and Where to Optimize Cell Culture MediaPosted 3 weeks ago
- Cool Tool – SCOUT® technology reduces time to market and increases chance of success for biopharmaceutical productsPosted 3 weeks ago
- Pumping Iron – But Not in the gym: The Critical Roles of Transferrin in Cell Culture MediaPosted 3 weeks ago
- Solve Production Challenges of Difficult to Express Proteins with Scalable, Continuous ManufacturingPosted 3 weeks ago
- Video Tutorial – Understanding Chemically Defined Media in BioprocessingPosted 4 weeks ago
- 2016 BioProcess International Award Winners – Upstream and AnalyticalPosted 4 weeks ago
Utilizing UVC LEDs in Biotech and Pharma – Paving the way to better instrument design and better manufacturing methods
A Guest Blog By Hari Venugopalan, Director of Global Product Management, Crystal IS
One of the transformations in medicine is the rapid growth in biologics whose 8% annual growth rate is double that of conventional pharma. Biopharmaceuticals could become the core of the pharmaceutical industry, but not without significant transformation in the laboratory.
In addition, labs are moving towards processing smaller quantities to reduce reagent and chemical costs. Smaller payer reimbursements to labs make the need to reduce costs the number one challenge. In areas such oncology, infectious diseases and stem cell biology, small samples rather than population averages can drive important aspects of normal and disease biology. The effort required collecting the samples means that researchers want to maximize the information that is gathered from a sample. This, in turn, requires that successful instruments will be able to perform more analyses with a single, smaller sample.
It should, therefore, not come as a surprise that cost, quality and accuracy are key targets for instrument manufacturers for biotech and pharma. Deep UV (UVC) LEDs are helping spectroscopy instrument manufacturers meet cost, footprint and small sample targets. For example, in microvolume UV-Vis used for DNA quantification, high intensity UVC LEDs offer shorter integration times and less noise to improve the accuracy when measuring small samples. In addition, UVC LEDs allow for simpler system designs which reduce the footprint and cost of the instrument.
UVC LEDs are also increasing reliability in biotech processing as well as process monitoring in pharmaceuticals. UVC LEDs enable longer instrument life, higher reliability, and increased productivity while reducing overall costs for the end user. These new devices are driving innovations in instrument design for the life sciences to address key market trends around productivity, cost reduction, and miniaturization.
DNA quantification relies on using absorption spectroscopy at 260 nm and 280 nm to determine DNA concentration and sample purity. The extraction of DNA ensures the integrity of biological research and impacts fields such as biotechnology, forensics, genomic research and pharmaceuticals. This includes the detection of genetic disorders, production of DNA fingerprints, and creation of genetically engineered organisms that can produce beneficial products such as insulin.
Manufacturers of these instruments have traditionally chosen xenon flash lamps as light sources for these applications. However, high performance UVC LEDs can better address some of the market trends owing to the inherent benefits of LEDs as a solid-state light source.
The drive to increase productivity and reduce costs in these applications centers on the speed and accuracy of measurement. Spectrometers for DNA concentration and purity measurements rely on xenon flash lamps, which offer instant on/off for quick evaluation with high linearity of measurement over a wide concentration range.
Although these lamps generate ample light across multiple wavelengths (a significant fraction of the optical energy is in the visible spectrum), DNA purity is determined by absorbance measurements taken specifically at 260 nm and 280 nm. Thus additional elements such as filters and mirrors must be used to filter out unwanted wavelengths before light from the lamp hits the sample. Xenon flash lamps also require high voltages and increased shielding of electronics during lamp ignition. These expensive electronics coupled with additional optical components quickly adds to the overall cost of the instrument.
Within the narrow range of wavelengths defined by the absorbance measurement for either DNA or protein, UVC LEDs can exceed the measurement performance of xenon flash lamps. Figure 1 compares the spectral irradiance of a 1 mW, 260 nm UVC LED with a 15 W Xenon flash lamp.
Figure 1: Irradiance
The high light output of the LED allows for a lower detection limit of 0.5 ng/µl for concentration of double stranded DNA (dsDNA) and the excellent spectral quality of the LED leads to linearity of measurement over three orders of magnitude of concentration from 0.5 – 2000 ng/µl (see Figure 2).
Figure 2: Linearity of Measurement
The monochromaticity of LEDs results in a simpler design than the xenon flash lamp instrument—one that requires fewer optical elements and therefore lowers system cost. Additionally, power sources for UVC LEDs are less complex, and less costly. The reduction in component costs allows for an instrument that costs 60% less than the xenon flash lamp-based version.
The efficiency of the system is also a factor that contributes to the overall costs. In the system examples above, the power consumption for the UVC LED system is approximately 2 watts (1 watt per LED). A typical xenon flash lamp will operate at an average power of anywhere from 2-60 watts. The higher power consumption of the xenon flash lamps also increases the operating cost.
Visible LEDs are well known for their long lifetimes. Although UVC LEDs are an emerging technology and the lifetime still does not match that of their visible counterparts, the lifetime does exceed that of existing UV lamps. The longer the life of the light source, the more measurements that can be taken without the additional cost of replacement light sources and added maintenance costs.
Even though the lifetime of a xenon flash lamp can be provided in hours (as seen in Figure 3), it is often represented in the number of flashes (or measurements) with a typical life of 1E9 flashes. For an on time of 1 millisecond per measurement, the typical lifetime of a UVC LED of 8,000 hours at 20 mA would translate to 3E10 measurements before requiring replacement. That’s 30 times more measurements than the xenon flash lamp.
Figure 3: Lifetime
Increasing reliability in biotech processing
Biotech manufacturing is a complex production process that tends to yield small quantities of drugs. Consequently, it is critical to avoid contamination and any yield losses during manufacturing
Connection points in the sampling device are the primary source of contamination. UVC LEDs are being used to sterilize connection points in biomanufacturing as an alternative to conventional sterilization methods. UVC LEDs offer compact, portable disinfection free from the additional issues of high temperature or chemical sterilization using hydrogen peroxide. UVC LEDs allow for the disinfection of multiple connection points simultaneously – increasing productivity by decreasing the cleaning time. The non-contact disinfection method does not leave chemical residues or traces on the equipment.
Improving quality & reducing costs in conventional pharma processing
Cleaning verification in the pharmaceutical industry helps to ensure patient safety through minimization of cross-contamination. The conventional method used is HPLC which is expensive and time consuming, and may require a halt to production till validation is complete. As drugs have become more potent, the active pharmaceutical ingredient (API) concentrations have become lower and limits for drug residue to meet cleaning requirements have gotten lower. Thus, new methods of cleaning verification which are more cost effective, faster and more sensitive are needed.
Light induced fluorescence of active pharmaceutical ingredient (API) in rinse water is emerging as an optimal in-line and/or at-line method for cleaning verification. In fluorescence, the emission intensity is proportional to the intensity of the LED excitation, and the availability of high light output UVC LEDs enables detection at very low concentrations. The in-line verification also minimizes impact to the manufacturing process and can be used to further optimize cleaning steps.
UVC LEDs can match and sometimes exceed the performance of lamp-based systems, while delivering higher efficiency and reduced costs for fixed wavelength applications. This allows the instrument designer to capitalize on the other benefits of UVC LEDs, such as cost and size, without sacrificing quality. These new devices are paving the way to better instrument design and better manufacturing methods in the life sciences.