Non-invasive screening tests for preventive healthcare

PHAGES PART 3 – Bacteriophages in screening and diagnostics

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In addition to their growing use as therapeutics for severe diseases, like super bacterias or cancers, phages have also another lesser known application area – diagnostics. Here the specificity of phages becomes an exceptional tool for screening for different diseases. Their natural capability to evolve and transform enables their use as bio modulators in our E-TRF method, allowing us to reach high specificity in detecting and classifying several different severe diseases. 

 

Biosensors, biosensing and biopanning

Because of their extraordinary specificity, phages have great potential as accurate biosensors. Biosensing is a process that combines a biological component with a sensitive biological detector or a receptor and a physicochemical element that produces a signal that can be measured. 

A good biosensor is accurate, highly sensitive, quick, reliable, and easy to operate. Bacteriophages as biosensors meet all these criteria. They are inexpensive, can withstand relatively harsh conditions, and are extremely specific and sensitive. Phages are stable, simple, and easy to handle. Their modifiability and other applications make it possible to develop label-free point-of-care biosensors able to detect disease biomarkers. 

The bacteriophage has a natural affinity towards its host bacteria. This affinity is provided by a specific region usually at the tail of the bacteriophage. In different applications, specific changeable regions of bacteriophages can be utilized in detection applications, like biosensors with different signal transduction options. In other words, the bacteriophage’s host specificity can be directed and modified towards different receptors and targets, which is why phages can be applied as biosensors to detect numerous different things.  

The phage’s affinity is modified through a process called biopanning. Biopanning imitates the process of evolution. In this case, the evolution is directed towards a chosen disease target. The phage’s affinity towards the specific targets, like disease markers, is amplified through a series of incubation, washing, amplification and re-selection rounds. The end result is a phage with a very strong attraction to very specific targets. For example, this method enables the phages to be sensitive to only lethal variants of prostate cancer, or to be able to differentiate between Ulcerative Colitis and Crohn’s disease. 

 

Aqsens Health’s application of phages for screening

Aqsens Health’s method utilizes bacteriophages in a novel way as biosensors in our screening tests. Our Chief Scientific Officer Janne Kulpakko has previously used biosensing phages to screen for urinary tract infections, and to classify e.g. prostate cancer variants. This technology is what Aqsens Health’s current research and development is partially built on.  

Aqsens Health’s use of phages is based on their modifiability, or “trainability”. Our patented method uses phages and biopanning processes to train the phages to be sensitive to two possible host molecules. 

The bacteriophages are biopanned to bind to quencher molecules or biomarkers. If a sample contains a disease biomarker, the phages bind to the biomarker leaving the quencher molecules free to move in the sample, affecting the sample’s color intensity. The change in color intensity is so strong it can be seen with the naked eye, or with a mobile phone. If a biomarker is not present, the phages bind to the quencher molecules and the color intensity of the sample does not change. 

 

Moving forward

Using phages as biosensors for screenings tests is much easier than using them as a treatment when it comes to the regulations set by the EU and the FDA. Because the phages do not make contact with the patient but only the sample, the regulations are not nearly as strict as they are when phages are used as a treatment for a bacterial infection. 

There are currently no phage-based sensing devices on the market, but in recent years several phage-based technologies have been patented, so the future of phages in biosensing looks promising. Bacteriophages have great potential both as an alternative to antibiotics as well as a biosensor in new and innovative diagnostics and screening methods. We are excited to continue our research into the use of phages in screening and hope to make more exciting discoveries in the future. 

 

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Sources:

Griesser, H (ed.) Thin Film Coatings for Biomaterials and Biomedical Applications. 2016. Woodhead Publishing. doi: 10.1016/C2014-0-01872-2

Biopanning. In: Encyclopedic Reference of Genomics and Proteomics in Molecular Medicine. Springer, Berlin, Heidelberg . https://doi.org/10.1007/3-540-29623-9_6317

Kulpakko J, Rantakokko-Jalava K, Eerola E, Hänninen PE. Rapid time-resolved luminescence based screening of bacteria in urine with luminescence modulating biosensing phages. Anal Biochem. 2019 Apr 1;570:21-26. doi: 10.1016/j.ab.2019.01.011. 

Peltomaa, R., López-Perolio, I., Benito-Peña, E. et al. Application of bacteriophages in sensor development. Anal Bioanal Chem 408, 1805–1828 (2016). doi.org/10.1007/s00216-015-9087-2

Lee JW, Song J, Hwang MP, Lee KH. Nanoscale bacteriophage biosensors beyond phage display. Int J Nanomedicine. 2013;8:3917-3925. doi:10.2147/IJN.S51894