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Kamasutra Inspired  Technology

Kamasutra Inspired Technologies (KIT)

Kamasutra, an inspiration for a paradigm shift in hyphenated technology!

Summary

Progress in life sciences requires more and more diverse data to enable specialists to make decisions that are relevant and help to improve our life. Kamasutra world's oldest book packed with wisdom about achieving a balanced and sensuous life between couples or groups. It teaches harmony between partners.  Exactly the opposite is currently happening in hyphenated technology where MS suppliers steer towards high cost - high resolution MS as a single technology.  “When the only tool that a man owns is a hammer, then every problem will resemble a nail!” Kamasutras wisdom inspires us to go beyond the obvious, to open-up our perspectives and to extend our skills in collaborating with other partners to extend hyphenated technologies into becoming multi data provider, being affordable and highly productive. The first Kamasutra inspired technology is MatrixEx.

Introduction

Modern Chromatography is more than 50 years old. Chromatography has emerged as the most important laboratory technology that is used in research and routinely in companies to separate, purify and detect molecular composition quantitatively and qualitatively for almost anything  solid, liquid or gaseous. Since 1980 we use the term Hyphenated Technology to describe two independent technologies that are coupled to work as one unit.
Today everybody is familiar with terms such as LC - DAD, LC - UV, LC - MS, IC -MS, SFC - MS, GC - MS etc.. The great advantage of hyphenated technologies is that they constitute a system based on various components. Multi component system can be developed further and they produce a wide variety of data very productively. Over the years we observe that advances in MS technology move away from hyphenated towards high cost mono- technologies.

Everybody is interested in “ foreseeing ” where a particular industry is heading. Nobody can predict the future since everybody is involved in shaping the future in the present. What we can do is to build scenarios of possible futures. Most companies / enterprises / institutions offer a product or service to finance their employees. The entity will disappear if no products and services are offered. Life and success follows a clear pattern we describe as product or enterprise life cycle.

Product Life Cycle small 1

A model of such product  / enterprise life cycle you may download by clicking here

In the real world  we have activities (Y axis, green) that change over time,  - over a virtual (X axis, blue) and over a real time (Z axis, red). Along the virtual time axis we list the general pattern of activities that follow a virtual time scale e.g. idea creation, basis research, applied research, start up formation, product development, market development and market exploitation etc. In the real world activities have a name and happen in real time dimension listed along the z-axis e. g. basic and applied research in chiral chromatography materials e. g. 1980 to 1995.
Depending on what we aim to achieve we look at and describe what happened in the past up to the present. We define our perspective e.g. as global onlooker, as niche product manufacturer,  as achieved academic in a particular field etc. 
A project always starts with an Ideas and a name or description of the idea. Research may start immediately after an idea is born or many years later because other projects have to be completed first to acquire the required basic knowledge. 

Quick look back into history

The analysis of complex mixtures requires the combination of both separation techniques and detection technologies such as hyphenated technologies. Early hyphenated or hybrid technologies were gas chromatography-mass spectrometry  (GC-MS) followed by liquid chromatography-mass spectrometry (LC-MS). Later came  capillary zone electrophoresis-mass spectrometry (CZE-MS), and supercritical fluid chromatography-mass spectrometry (SFC-MS).  Hyphenated technologies were introduced into more and more different application.

Development in Mass Spectrometry has commenced more than 100 year ago and its achievements in the past 20 years are remarkable.  Since invention of Orbitrap analyzer and its proof-of-principle by Makarov  by 1990 MS technology has gone through meteoric growth. In such exciting time times particularly in the life sciences there are often a number of vanguard researchers mainly in Universities that compete with each other and some advance to become leading pioneers in the field. In this competitive race they have to focus their activities and to create  highly specialised technology. Some of the pioneers are being discovered by the professional media, the general media and government.  Some become important influencers at government level.  Soon their ideas are being specified  to be used in public sector. Through that mechanisms often research is “industrialized”.  In the commercial world there are technology suppliers and technology users. The suppliers compete with other suppliers and users compete with other users.  To reduce competition financially strong suppliers buy other suppliers with a strong market presence.  In the past twenty years  five to six companies have grown to very large system suppliers.  Besides the few very large enterprises there are  about 70 to 80 small enterprises, often privately owned  that focus on development of unique technologies and niche products and services. 

In the last few years competition amongst system suppliers is growing. In the past they collaborated with other companies but this is gradually disappearing to become monolytic and closed entities. With their financial power they control technology development in various universities. There is also a trend to move away from hyphenated system and to sequentialize some technologies and to disable access to the the software.
Progress is driven by research and competition. Hyphenated technologies are still quiet young. Looking at the demand side in the market we have a large spectrum of new and very complex fields that require sophisticated separation and molecular sensing technologies.  Users should undertake everything to prevent monopolization of the market.   Already in the past there were attempts to eliminate hyphenated technologies.  During the nienties specialists at University of Virginia introduced use of MS/MS for obtaining amino acid sequences in peptides. They proclaimed that henceforth one would need only two theoretical plates of chromatography prior to the MS; one peak with the peptides whose sequences one wished to obtain and a second peak with the salts and other junk that one wanted to keep out of the MS. This approach worked well until people started trying to analyze samples with more than 30 or 40 peptides, at which point suppression of ionization became an issue. The pioneers at University of Virginia stuck a C-18 capillary in front of the mass spec. This then served well enough for samples up to about 400 peptides, until around 1997. At that point a Post Doc, Dr John Yates at the University of Washington wanted to separate samples with over 1000 peptides, and ion suppression issue was once again the limiting factor. The company PolyLC told him that he needed to distribute his peptides into smaller subsets, each one of a size that the C-18 capillary could handle. They supplied Polysulfoethyl A, a strong cation exchange column (SCX) that was able to bind all peptides and whose selectivity was complementary to that of RPC.  Yates published that SCX-RPC combination in a paper in 1999 which served as the role model for how bottom-up proteomics has been done ever since. 

We need new ideas and new surprises to tackle new and increasingly complex problems.

Looking into future we are witnessing the following technology based trends, -

  1. Costs in life and food sciences and technologies have risen more then in other industries. Cost for launching a new active pharmaceutical ingredient was 1995 approx USD 450 Millions. Today twenty years later the costs for the same task is USD 4.8 Billions. The under-laying cause of this cost explosion is growing complexities and the need for employing specialist that understand how to deal with the complexities. Specialist have highly focussed knowledge and skills but they dont understand the skills of their up- and downstream specialist partners. Product development happens through a chain of specialists that compete with each other. Statistics tell us that every second developed product is a flop.
    Managers are trying to reduce cost with fairly simple strategies. They install low cost routine workers and minimize amount of suppliers and range of product procured.  This way they reduce the department costs but dramatically increase hidden cost combined with a loss of productivity. In the real world molecules and molecular mixtures becoming more and more complex. Many companies are shifting from small molecules to biologics and this is also a shift towards more complexity. Consequently, the strategy of simplification is going into the wrong direction.  Motivating and empowering people to show more courage to address and solve complex system problems will decrease flops and development cost.
  2. Progress in life science research and product development combined with improvements in hygiene will lead to better health and longer life. Growth in the emerging market will continue and to spread into Africa and South East Asian countries.  The market for pharmaceuticals, med-tech products and diagnostics will continue to grow and so will the need for competitive and robust separation; purification and detection technologies.  Governments in the emerging economies will motivate investors to  finance the emergence of new generics manufacturer so as to reduce dependency on the large global pharmaceutical and bio-pharmaceutical suppliers and to reduce pressure on balance of trade.  In the post- industrial economies  the  life science sector has to focus on  R & D of complex knowledge based products and services.  Registration authorities will face to approve and certify novel  technologies. To reduce risks of failure registration authorities will demand more and a broader diversity of test and data.
  3. Late 1990 early 2000 the buzzword Genomics and proteomic appeared. The list was soon expanded to Transcriptomics, Metabolomics, Lipidomics, Glycomics, Foodomics and Sportomics. The list is still growing and a clear taxonomy is missing.  As time goes past the complexity of omic research is growing.  All this fields are big data sciences that have a high demand on reproducible and reliable separation, purification and detection technologies. In some of fields we a moving fast into an application mode while in other we dont now where to start.
  4. In Proteomics we are witnessing a shift from basic research environment into more applied laboratories where user requires less complicated tools that provide more application related information for a affordable price.
  5. Metabolomic research has just only started. It is about measuring biochemical molecules in organisms, - not what they can do but what they do.  We have to deal with ionic, non-ionic, hydrophilic, hydrophobic, chiral, large, small etc etc molecular species. At this point in time many different techniques are being used. This in turn requires a broad range of skills and strong data collection and crunching facilities.  One day in future the medical doctors want to use this technology as diagnostic and therapeutic tool.
  6. The dietary supplement industry has grown to become a multibillion-dollar-a-year market. Concurrent with this growth, the FDA has implemented new current good manufacturing practices (cGMP) regulations that mandate appropriate quality control and process control testing for dietary supplements, from incoming materials to finished goods. One of the most important tools used in quality control of dietary supplements is chromatography. All types of chromatographic methods have to deal with what some are now calling the most complex sample matrices ever encountered.
  7. In chemical synthesis chemists produces target compounds and by-product including some undefinable garbage.  At the moment chemist use flash chromatography to separate the target molecules from the rests.  With the grow in complexity of molecules we have a decrease in yield of target molecules and an increase in analogues and by-products.  One day the drug discovery community we will realize that analogues and  by products may also have some value or even bioactivity.  It is only a mater of time until we discover harvesting and screening those of by products.  is improving our efficiency and effectiveness. Flash chromatography will be replaced with modern separation technologies and
  8. In comparison to research institutions commercial  companies use chromatography to provide an important service for many different clients. Unfortunately they also have to compete with others and have to depreciate their equipment before they are able to procure the next generation. They simply can’t invest millions to build up their services. They are under permanent pressure to reduce running cost and to keep the equipment as long as possible.
  9. With growing complexity of molecules we are moving a way from recrystallisation to new purification strategies. During the past 20 years progress in production scale chromatography is mediocre and lacking of visions.
  10. Separation / purification  and detection technologies are based on chemical engineering principles and laws of physics. Many parameters such as high temperature, use of sound and light, solvent reduction strategies, ionic liquids, electrical fields, different column and material constructs etc. have been evaluated in research in the past but very few reached the commercial world. Today 80% of columns used in the life sciences are based on reverse phase chemistry. Most compounds also carry polar and ionic charges that could be utilised for better separations. Unfortunately Chromatographers are afraid to experiment with selectivity options and they hold back on applying new technologies to improve productivity or process uniqueness. The industry benefits from fairly long patent life cycle. Managers dont realize that patent life could be extended by a few years and transition into generics slowed down through process uniqueness.  Such a strategy would enhanced profitability dramatically. 

 The Future

Nobody can predict the future - but we are able to create and shape our future. The future trends are loud and clear - we have to cope with more complex molecular mixtures and to extract more data, information and knowledge from the molecular mixtures,  faster and at lower costs!

Instead of reducing hyphenated technology back to single purpose technologies we have to move forward and to increase diversity of the hyphenated technologies. Hyphenated technologies are like  couples that empower each other to excel. They are effective and competitive because they function as a unit. Kamasutra is world's oldest book packed with wisdom about achieving a balanced and sensuous life between couples or groups. It teaches harmony between partners. Kamasutra is a tremendous source of inspiration for advancing effectiveness and efficiency in hyphenated technologies. It inspires partners to experiment together to enhance life for both. This will lead to a more aware and fulfilled life. Kamasutras wisdom urges us to go beyond the obvious, to open-up our perspectives and to extend our skills in collaborating with other partners. Kamasutra is an inspiration for a paradigm shift in hyphenated technology!

Inspired by Kamasutra we focussed on output performance and value creation, on issues that are of interest to down stream partners, - the users.  Our clients like to demonstrate to their clients that they are competitive, productive and equipped to cope in an increasingly complex world. Following Kamasutra’s wisdom this is only possible if both parts in front and after the hyphen are being advanced to become most cost effective and to produce more value.

Four years ago we started to create our first “Kamasutra Inspired Technology ™” platform that applies Kamasutra wisdom in hyphenated technologies. The platform is a new tool that enhances existing hyphenated separation and detection systems to become more competitive and productive.

Kamasutra’s wisdom accepts both the Separation and the Detection side as equals. Thus the new tool is placed in between the LC and MS  to enhance the weaker partner and to coordinate both. In this position it is possible to automate processes so that the end-user can use his valuable time for method development or customer acquisition.

Kamasutra’s wisdom also allows to extent partner count provided both key partners accept and additional partner. Thus with Kamasutra Inspired Technology™ we can expand the platform to become a competitive tripartite construct that provides the end user more knowledge and value.

After four years of development we have today the first tool based on Kamasutra wisdom, - an exciting, competitive process for Pesticide Analytics which offers fully automated and highly intelligent multi column processing.  With every sample injection the sample matrix is removed so that the chromatographer commence with every additional sample injection with a totally clean column. This assures precise and reliable data and extended column life. Detail of this process you find under MatrixEx 

Proteomics is now entering industrialization. Demand for cost competitive systems that provide more information output is growing. Interested clients should contact us to discuss and participate in the evolution of the new Kamasutra Inspired Technology™. Please contact us without any obligations. click here

We also like to talk to Researcher in Metabolomics, Natural Products Discovery, Clinical Laboratories, Medicinal and Combinatorial Chemists about application specific platforms that can be installed or combined with your current resources. Please contact us without any obligations click here

 

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