Best Instrument

TSip™ (Tip Sealing Intellectual Property) UHPLC fittings developed by Best Instrument, Inc.


Overview TSip™ fitting development

Overview TSip™ fitting development

The Tip Sealing approach is important to the attainment of the goals of UHPLC, namely,
  • Reduced environmental impact due to reduced (perhaps 90% less) solvent useage.
  • Reduced cost of analysis due to reduced solvent useage.
  • Reduced cost of analysis due to reduced time of analysis.
  • Increased usefullness of scientific data due to improvements in resolution.
In addition to these goals, the Tip Sealing approach (as described in this 2007
patent publication) provides two key advances in the state of the art in sealing the ubiquitous 'HPLC port'.
Animation Pre-UHPLC
Dispersion of PRE - 'First Generation' UHPLC fittings

This figure shows two effects which are inherent to the port. First, a sample (blue) in injected in the solvent stream. Both dilution and tailing are shown by how the (cyan) sample behaves. For good measure, slipping is shown. Finally the animation repeats.

The effect of tubing slipage on column resolution is shown
here.

As instruments become more capable of UHPLC resolutions (whether or not operating at high pressures) it is of significant economic interest that uncertainties of 'connection' issues be minimized, since dispersion variance can lead to significant amounts of lost time in diagnosing system problems. Further, it seems intuitive that method validation protocols must take variability of extra-column dispersion into account, therefore, to reduce this cost, fittings which allow for greater possibility of extra-column dispersion variance should be minimized.


Animation Pre TSIP
'First Generation' UHPLC fittings

The so-called 'First Generation' UHPLC fittings have a common element, that is they use a cone-shaped ferrule to acheive a pressure seal. There are variations in the design of this ferrule, but with each design, the primary method to reduce dispersion is to attempt to 'bottom' the tubing in the port, thus minimizing swept dead volume. However; this first generation is subject to the uncertainty of 'indeterminate sweeping' of the cylindrical dead volume surrounding the tubing (at the port bottom).

It is speculated this thin cylindrical volume may not neccesarily be universally swept or unswept. Since no provision is made to attempt to seal the microscopically rough bottom of the port, pressure fluctuations in the flow path could conceivably communicate sample into this volume. This 'thin cylindrical volume' can easily be in the 400-600 nL range using measurements of typical ports. Some manufacturers appear to be aware of this possibility and minimize the diameter of the port such that it more closely matches that of the tubing. This 'tight fit' is desireable, but special care must be taken in design of TSip™ style fittings to avoid 'sticking' of the tip, as has been observed in early TSip™ prototypes.


Animation TSip
Tip Sealing TSip™ method

Additional arguments for TSip™ styles are based on the number of potential re-uses of TSip™ fittings. The actual cost of fittings per instrument on a per-use basis now favors the TSip™ technology. This applies to all high resolution methods, those at high and low pressures. Lastly, the actual time and 'fussiness' required to make a consistent connection with 'First Generation' UHPLC fittings necessitates significant operator awareness and training on the use of the fittings themselves. The TSip™ style fittings finally return to the old and simple rule of merely "tighten a fitting until is does not leak, no more". This rule applied nicely 20 years ago, and applies again today. But through the era of 'First Generation' UHPLC fittings (cone ferrule types), the persistance of the rule (tighten till the leak just stops) may have been responsible for significant 'finger pointing' as UHPLC resolutions were improved. This 'finger pointing' refers to falsely blaming wither the column or instrument for inconsistency of performance which may have ben attributable to 'complex' fittings.


Group of first generation UHPLC fittings
Figure: Four embodiments of the TSip™ method
This series shows 4 variants of body styles, and the two major methods of Tip Sealing as claimed in US patent 9217522. They are not positioned chronologically, but the enumeration is chronological in terms of prototype fabrication and testing.


TSip™ basic implementation components

TSip™ basic implementation components

Required components
Figure: Minimum components for simplest implementation.
The components are...
  • 1. The seal. Designed to seat at the bottom of the port.
  • 2. Linking tube. Crimps around seal and tubing.
  • 3. Fitting body. Can take a variety of forms, but uses linking tube to press seal 'down and around' the tubing.
  • 4. Small diameter tubing. Can be PEEK, Fused Silica, Stainless steel, or other.
  • 5. Jacket. Loose fitting PEEK. Not called out in patent for TSip™, but very practical to protect fused silica tubing.
Optimized geometries of components 1 and 2 are necessary to acheive...
  • maximum operating pressure
  • minimum dispersion
  • stick free design
  • long life, and
  • ease of assembly
Optimized geometries of component 3, the body, is necessary to acheive...
  • Avoidance aganst overtightening (for long seal life)
  • Adequate tightening force, and
  • general ease of use
There are many possible configurations of the body which satisfy these requirements.

Grey Seal Manufacturing

Grey Seal Manufacturing

Crimpers amd components
Figure: Components manufactured by lathe to allow experimentation with optimized geometried of components.

The array of TSip™ body parts, Tip Seals, Linking tubes, and bodies, were CNC machined using a Citizen B12 Swiss Lathe (Japanese), or EMCO Super 11 (Austrian). Many design teams might elect to proceed directly to injection molding of the seal component, but by taking the intermediate prototyping step, a variety of slight variants, particularly of the seal, were possible. This allowed very low cost correction of design oversights such as those surrounding the precise shape and dimentions at the critical sealing area. Oversights in this area can not only lead to poor performance, but to very annoying problems such as a seal becoming stuck in a port.

Also shown are: