Quadrupole and Time of Flight Mass analysers.

Description about important mass analysers Quadrupole and TOF: Principle, Construction and Working, Advantages and Disadvantages and their Applications.

1. Topic : Quadrupole and Time Of Flight mass analyzers Presented by: Ramesh S. Gagan S. Dept. of Pharmacology. Dept. of Pharmaceutical Chemistry Government college of Pharmacy, Bengaluru. Mass spectroscopy

2. CONTENTS Introduction Principle Theory Construction and working variants Advantages Disadvantages Applications

3. INTRODUCTION Mass spectrometry is an analytical chemistry technique that helps identifying the amount and type of chemicals present in a sample by measuring the mass-to-charge ratio and abundance of gas phase ions.

4. Typical representation of mass spectrometer

5. MASS ANALYSERS Mass analysers are called heart of mass spectrometer . These are the instruments which separates the mixtures of ions that are generated during the ionization step by m/z in order to obtain a spectrum.

6. Types of mass analysers Magnet sector mass spectrometer. Quadrupole mass spectrometer. Ion trap mass spectrometer. Time of flight mass spectrometer. Fourier transform mass spectrometer.

7. Table : Summary of mass analysers . MASSS ANALYSER MASS RANGE RESOLUTION SENSITIVITY MAGNETIC SECTOR 1-15,000 m/z 0.0001 Low QUADRUPOLE 1-5000 m/z Unit High ION TRAP 1-5000 m/z Unit High TIME OF FLIGHT Unlimited 0.0001 High FOURIER TRANSFORM Up to 70 k Da 0.0001 High

8. QUADRUPOLE MASS SPECTROMETER Quadrupole mass analysers concept was first reported by Paul and Steinwedel in the 1950s. Quadrupole consists of four rods which are arranged parallelly. Rods opposite to one another are electrically connected. Ions are separated based on m/z at a particular DC and Radiofrequency voltage.

9. PRINCIPLE: . IONS FROM THE IONS SOURCE QUADRUPOLE ANALYSER WITH A CONSTANT DC AND RF VOLTAGE AT GIVEN COMBINATION OF DC AND RF VOLTAGE IONS WITH CERTAIN m/z VALUES REACH THE DETECTOR IONS WITH DIFFERENT m/z VALUES TRAVEL UNSTABLE PATH

10. CONSTRUCTION:

11. . It consists of four electrically conducting parallel rods. One diagonally opposite pair of rods is held at + Udc volts and the other pair at – Udc volts. A radiofrequency oscillator supplies + Vcos ω t to the first pair and – Vcosωt to the second pair. Ions enter to the quadrupole through a circular aperture.

12. WORKING: When ions enter into the quadrupole ions get deflected by the positive and negative electrodes and ion with a certain m/z value will reach the detector. This can be explained by taking individual pair of rods.

13. Rods connected with +DC and +RF Voltage :

14. Rods connected wit –DC and –RF voltage

15. In combination of both the pair of rods

16. Example:

17. FACTORS AFFECTING FUNCTION OF QUADRUPOLE: Focussing slits Rod length Rod diameter Increased rf frequency

18. ADVANTAGES: High sensitivity. They can operate close to ground potential. Ideal for interfacing to LC system and for atmospheric pressure ionization (API) techniques such as electrospray. Well suited for the negative ions ,since the analyser does not discriminate between the polarity of the ions. Economic, robust and scanning is very fast.

19. DISADVANTAGES: Quadrupole is generally inferior to magnetic sector analyser with respect to resolution and mass range. Peak height variable as a function of mass. Not well suited for pulsed ionization methods.

20. APPLICATIONS: In liquid chromatography-Mass spectrometry. In Gas chromatography-Mass spectrometry. To measure the relative amounts of different gases in a mixture. Proteomics.

21. TIME OF FLIGHT MASS SPECTROMETR Introduction: Stephens first described the concept of time of flight in 1946. As the name implies, time of flight mass spectrometer separates ions and measure their m/z based on the time they take to pass ( “fly” ) from the ion source to the detector.

22. PRINCIPLE: Ions with different masses and same kinetic energy travel when accelerated and the ions with smaller masses (less m/z value)reaches early to the detector than the bigger masses .

23. THEORY: The kinetic energy of ions of mass (m), charge (z) and accelerating potential (V) is given by KE = zV = ½ mv 2 (1) Where (v) is velocity of the ions which is given by v = l/t where, l = length of the tube t = time taken by the ions to pass the length of the tube Therefore, equation 1 becomes zV = ½ ml 2 /t 2 m/z = 2Vt 2 /l 2 2V/l 2 = k (constant) therefore, m/z = kt 2 m/z α t 2

24. LINEAR TIME OF FLIGHT MASS ANALYSER Construction:

25. Working: . IONS FROM THE ION SOURCE TOF ACCELERATION OF IONS ACQUIRES DIFFERENT VELOCITIES SPATIAL SEPARATION OF IONS IONS WITH HIGHER VELOCITY REACH THE DETECTOR FIRST

26. VARIANTS OF LINEAR TOF ANALYSER Ion mirror / ion reflectron / reflectron . Time-lag focussing

27. NEED FOR VARIANT TYPE OF TOF ANALYSER Ions with very similar m/z ratio may have relatively poor mass resolutions . This is due to the spatial distribution in the ion source and their proximity to the applied electric field, not all the ions receive the same kinetic energy. This leads to components in mixtures being unresolved from one another and large errors in molecular weight measurements.

28. ION MIRROR / ION REFLECTRON / REFLECTRON Construction and working:

29. . It consists of stack of donut shaped lens connected by a series of resistors across which voltage is applied. These lenses repell the ions entered. These ions are reflected down at second flight tube to a second detector. Mass resolution is achieved as ions of different kinetic energies penetrate the mirror to differing degrees .

30. . For example consider two ions of the same m/z ratio that have slightly different kinetic energies.

31. TIME-LAG FOCUSSING / PULSED ION EXTRACTION / DELAYED EXTRACTION Construction and working:

32. . In time-lag focusing TOF applying accelerating potential is delayed. Ions from the ion source will have some kinetic energy and moves with different velocities Application of potential gives more energy to the ions which are away from the detector than closer to it. The amplitude is adjusted in such a way that all the ions reach the detector at the same time.

33. ADVANTAGES OF TOF MASS ANALYSER Mass range is unlimited. Excellent sensitivity due to lack of resolving slits.

34. DISADVANTAGES OF TOF MASS ANALYSER Limited use in case of pulsed ionization techniques. Mass resolution is usually less than 20000. Fast electronics are necessary for adequate resolution.

35. APPLICATION OF TOF MASS ANALYSER Due to its fast scanning capability it is increasingly being used in LC-MS instrumentation. Generally it is used in case of fast analysis or in high chromatographic resolution techniques.

36. REFERENCE: Spectrometric identification of organic compounds by Robert M Silverstein and Francis X Webster,pg . no. 10-12. Instrumental methods of analysis ,7 th edition by Willard Merrit Dean Settle, pg. no. 480-483. Instrumental analysis by Skoog, Holler, Crouch, India edition pg. no. 627. Mass spectroscopy, A foundation course by K.Downard , pg. no. 40-43. Organic spectroscopy, William Kemp, Third edition, pg. no.286-288 An introduction to Quadrupole Time of flight mass spectroscopy ,Journal of mass spectroscopy, Willey analytical science.

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