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FLUOROBOT the „Tata Nano of TB Diagnosis”

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FLUOROBOT the „Tata Nano of TB Diagnosis”. An axample of Frugal Engineering. 
(Notes from the CEO)

A book review has struck my eyes a few weeks ago, in a medtech newsletter, that I receive regularly and find very useful. It appeared on the occasion of a book published recently by Peter Blair Henry: „Third World Lessons for First-World Medical Technology” 

The reason why I am glad that this topic hits the Medical Technology Industry (which in developed markets was rather „spoilt” earlier, with high budget institutional buyers) is because that is exactly what we followed in the Fluorobot development process

The author of this article – Norbert Sparrow, author of many thoughtful publications in medtech subjects – also quotes a panel discussion, with Carlos Ghosn among others, the „father” of the Frugal Engineering.

If you become hooked on about this engineering philosophy, as I have become since we restarted the Fluorobot project, you may find earlier publications very instructive, such as „The Importance of Frugal Engineering” by Vikas Sehgal, Kevin Dehoff and Gamesh Pamneer, which you may find in „Strategy-Business”  .

When we have restarted 4 years ago, we have spent more then a year just by optimizing the optical path – for one magnification, one set of optical elements, (objective, filters), maximal signal/noise ratio – instead of „stripping down” existing commercially available components, such as a piezo moving stage or a multipurpose microscope design. This is exactly what frugal engineering suggests, instead of cutting existing costs (multipurpose microscope) avoid needless costs in the first place We do not even claim Fluorobot is a microscope, it s a TB Screener – and in my mind it is the Tata Nano of TB Diagnosis. And to me, it is my conviction that this is not a synonym of „cheap, low-end” product, but that of clever engineering, and humble understanding of your market.

The basic philosophy of frugal engineering – doing more with less resources – has so strongly influenced project management and our developers’ team, that we knew if we do not succeed (come up with an affordable solution, good enough to carry out the automatic sputum smear screening watching our unit cost counter very closely) we will fail the whole project. And that is why we believe today, we have the only „Frugal TB Screener” in the world, instead of another experimental setup, seen at University Laboratories or elsewhere, which are going to find it difficult to be affordable in most of the cca. 80 thousand microscopy laboratories worldwide, most of which are in resource limited settings. They can of course solve the problem (it is no doubt possible with state of the art image processing of today) but keep such a long-awaited solution on this unmet market segment, out of reach of those laboratories, which are in greatest need, and can not even dream of being able to invest into more sensitive but expensive methods, such as Culture or Molecular Diagnostics.

Last but not least, besides our talented engineering teams, this has become possible by  listening to so many experts from the field. Input from senior microbiolgists from India to Brazil and organizations being active in delivering solutions to cure TB to the Third World, and the experts working for such organizations. When we first presented the functional model of our original design, we believed will be enabling us to come up with a TB Nano, we got the clear message:

if we can not hit the price barrier these laboratories are limited to, we will not have a product for this market, that will sell.

And to add a last comment, we are working with several Indian suppliers, to whom we never had to explain what we need. 

Donat Kiss
CEO

Fluorobot History

FL_history

The management of ASK (who were the founders of ConsultASK in 1999) were approached by the Semmelweiss University of Medicine Department of Respiratory Medicine in 1995 ( Dr. Ákos Somoskövi, Prof. Magyar) to develop an automated robot microscope with imaging for detection of AFB in fluorescent stained sputum smears, based on the reputation obtained in robotic light microscopy with successful projects such as the urine sediment analyzer, Seditron.

A prototype was developed in 1996, and a clinical study at the University Laboratory was conducted with 132 + 107 smears, parallelly tested with Ziehl-Neelsen staining and manual microscopy.

Smears of specimens and liquid media stained by the ZN method were examined at 1000_immersion magnification, three sweeps being made along the longest dimension.

A negative result was reported after the examination of 200 immersion view-fields

A computer automated fluorescence microscope was constructed for detection of the presence of AFB in auramine-O stained smears. Auramine-O stained smears of specimens and broths were examined with the automated microscope.

All auramine-O stained AFB-positive smears were restained by the ZN method to determine the accuracy of the examination.

The Results

A total of 132 sputum smears and 74 liquid media smears were examined in parallel by manual and automated microscopy. Conventional microscopy detected 53 positive and 79 negative smears of sputum, while automated microscopy detected 55 positive and 77 negative smears of sputum. Fluorescent smear positivity could be confirmed by ZN restaining and Bactec and LJ culture in all samples. Results of sputum smears are listed in the Table. Of the 74 smears of liquid media, 50 were found positive by both the automated and the manual version. The positivity of these smears was confirmed by LJ subculture. In the remaining 24 smears, automated microscopy did not detect any AFB, while the ZN smears revealed non-mycobacterial contamination.

 

Automated microscope positive

Automated microscope negative

Total

ZN positive

53

0

53

ZN negative

2

77

79

Total

55

77

132

The results were convincing and were presented at several meetings and introduced to WHO

  • ICEPT 97 International Congress on The Evolution and Palaeoepidemiology of Tuberculosis, 1997 Szeged, Hungary
  • Poster at Conference on Global Lung Health and the Annual Meeting of the International Union Against Tuberculosis and Lung Disease, October 1997, Paris
  • Results were published in Int. J. Tuberc Lung Dis, 1999 by the team

     

     

     

     

     

     

     

TB Diagnosis

Worldwide_TB

The TB diagnostic market has several traditional segments, and the molecular diagnostic methods, that became available recently. Manual sputum smear microscopy is the most widely used screening method for TB screening of suspected patients, as it is the most affordable and often the only accessible method in low resource environments, resulting in over 87 Mi determinations in 2008, with WHO estimations of 200m necessary determinations to be reached by 2020.

Widespread use of the “culture method”, the diagnostic process, considered as the gold standard due to its higher sensitivity, is limited by its high instrument costs, laboratory infrastructure need and a long time-to-result (several weeks).

The traditional X-Ray method is also instrument intensive, hence costly and of limited specificity, while the skin probe method is mainly used for screening latent TB as it is of limted sensitivity.  

Serology based rapid tests have been recently banned by WHO, in a „first ever” negative policiy statement issued in 2011.

The widespread use at lower levels of the healthcare diagnostic pyramid of the most sensitive and specific molecular diagnostic method is constrained by its considerable price per diagnosis, high level of complexity, a resulting biohazard environment, as well as the requirement of highly trained personnel. Consequently, this method is rolled out for complex, HIV infected, drug resistant determinations, normally subsequent to traditional pre-screening examinations (such as smear microscopy).

The Tireless Technician !