	US 12,074,015 B2
	Method for calibrating at least one mass spectrometry device
Andrea Geistanger, Munich (DE); Daniel Intelmann, Schaftlach (DE); Shirin Shahriari, Munich (DE); and Anton Hilger, Munich (DE)
Assigned to Roche Diagnostics Operations, Inc., Indianapolis, IN (US)
Filed by Roche Diagnostics Operations, Inc., Indianapolis, IN (US)
Filed on Jun. 2, 2022, as Appl. No. 17/805,133.
Application 17/805,133 is a continuation of application No. PCT/EP2020/086411, filed on Dec. 16, 2020.
Claims priority of application No. 19216965 (EP), filed on Dec. 17, 2019.
Prior Publication US 2022/0293404 A1, Sep. 15, 2022
Int. Cl. H01J 49/00 (2006.01)

CPC H01J 49/0009 (2013.01)

13 Claims

1. A method for determining a concentration of an analyte in a sample, wherein the method comprises the following steps:

i. conducting a method for calibrating at least one mass spectrometry device having a first defined hardware configuration, the method comprising:

a) at least one manufacturer-site pre-calibration step, comprising:

a1: establishing at least one reference calibration function f_pfor a generic type of mass spectrometry devices having a second defined hardware configuration, wherein the second defined hardware configuration is equivalent to the first defined hardware configuration, wherein the reference calibration function f_pdescribes a relationship of at least one concentration c of at least one analyte in at least one calibrator sample, wherein the reference calibration function f_pis a parametrized function

f_p(concentration)

with p=(p₁,p₂, . . . p_n) being a set of parameters of the reference calibration function and n being a positive integer;

a2: determining calibration values p=(p₁, p₂, . . . p_n) for the set of parameters of the reference calibration function for the generic type of mass spectrometry devices;

b) providing to a customer of the mass spectrometry device at least the following: the reference calibration function f_pfor the generic type of mass spectrometry devices, the calibration values p=(p₁,p₂, . . . p_n) for the generic type of mass spectrometry devices, and at least one calibrator sample with defined target value of the at least one analyte; and

c) at least one customer-site recalibration step for the mass spectrometry device, comprising:

c1: performing at least one calibration measurement using the mass spectrometry device and the calibrator sample, thereby generating at least one calibration signal;

c2: generating calibration information based on the calibration signal, wherein in step c2 the calibration information based on the calibration signal is generated by adapting the calibration signal to the reference calibration function f_p, wherein the calibration signal are converted into a theoretical signal

g_q⁻¹(calibration signal)=theoretical signal,

wherein g is the signal adjustment function defining a relationship between signals of the mass spectrometry device and a theoretical signal of the generic type of mass spectrometry devices and q=(q₁, q₂, . . . q_m) are calibration values of the signal adjustment function, wherein this theoretical signal is transformed into a concentration value by applying the inverse of the reference calibration function

f_p⁻¹(theoretical signal)=concentration;

ii. conducting at least one measurement comprising measuring the analyte in the sample by using the mass spectrometry device thereby receiving measurement results;

iii. adapting the reference calibration function f_pbased on the measurement results or adapting the measurement results to the reference calibration function f_p;

iv. determining the concentration of the analyte based on the measurement results.