System and methods for bilirubin analysis

• US 10,371,707 B1
• Filed: 04/03/2019
• Issued: 08/06/2019
• Est. Priority Date: 08/30/2017
• Status: Active Grant

• Current Assignee: NeoLight, LLC
• Original Assignee: NeoLight, LLC
• Inventors: Palaniswamy, Sivakumar, Krishnaraju, Deepakshyam, Peacock, Martin
• Primary Examiner(s): Xu, Xiaoyun R
• Application Number:
  US16/374,234
• Publication Number:
  US 20190234969A1
• Time in Patent Office: 125 Days
• Field of Search: None
• CPC Class Codes: B01L 2200/04 Exchange or ejection of cartridges, containers or reservoirs
• CPC Class Codes: B01L 2200/147 Employing temperature sensors
• CPC Class Codes: B01L 2200/16 Reagents, handling or storing thereof
• CPC Class Codes: B01L 2300/021 Identification, e.g. bar codes
• CPC Class Codes: B01L 2300/0645 Electrodes
• CPC Class Codes: B01L 2300/0681 Filter
• CPC Class Codes: B01L 2300/0883 Serpentine channels
• CPC Class Codes: B01L 2300/18 Means for temperature control
• CPC Class Codes: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: G01N 27/308 at least partially made of carbon
• CPC Class Codes: G01N 27/3277 being a redox reaction, e.g. detection by cyclic voltammetry voltammetry per se G01N27/42, G01N27/48
• CPC Class Codes: G01N 27/48 using polarography, i.e. measuring changes in current under a slowly-varying voltage
• CPC Class Codes: G01N 2800/085 Liver diseases, e.g. portal hypertension, fibrosis, cirrhosis, bilirubin
• CPC Class Codes: G01N 2800/52 Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 33/49 Blood chemical methods for determining blood cell populations G01N33/5094; chemical analysis of blood groups or blood types G01N33/80
• CPC Class Codes: G01N 33/728 Bilirubin; including biliverdin

Abstract

A method for measuring bilirubin levels in a subject. The method can include the steps of providing a sample to be measured from the subject, wherein the sample comprises bilirubin bound to albumin; adding a release agent to the sample, the release agent configured to release the bound bilirubin from the albumin; measuring electrochemical data of the sample using an electrochemical cell; and determining a total serum bilirubin concentration of the sample using the electrochemical data. This method is capable of providing a simpler, faster, and more robust measurement when compared to traditional bilirubin assay methods.

Claims

1. A system for electrochemical detection of total bilirubin, the system comprising:

a microfluidic device configured to receive a fluid sample, wherein the fluid sample comprises bilirubin bound to albumin, the microfluidic device comprising;

a preparation zone configured to combine the fluid sample with a release agent in order to release the bound bilirubin from the albumin;

a sensing zone having multiple electrodes and configured to provide electrical energy from the electrodes to the fluid sample; and

a controller in electrical communication with the electrodes and configured to;

control an electric potential on at least one of the electrodes; and

receive an electrical energy and provide information regarding a total serum bilirubin concentration in the fluid sample wherein the multiple electrodes are screen printed electrodes.

2. The system as recited in claim 1, wherein the fluid sample is an untreated blood sample of the subject.

3. The system as recited in claim 1, wherein the release agent is in the form of a dry solid.

4. The system as recited in claim 1, wherein the controller is further configured to provide additional information regarding the concentrations of conjugated bilirubin, unconjugated bilirubin, and albumin.

5. The system as recited in claim 1, wherein the release agent is cocamidopropyl sulfobetaine, 3[3-Cholamidopropyl)-dimethylamminonio]-1-propanesulfonate, 3-[3-Cholamidopropyl)-dimethylamminonio]-2-hydroxy-1-propanesulfonate, cocamidopropyl betaine, caffeine, sodium benzoate, sodium acetate, ethylene glycol, hexadecanoic acid, (9Z)-octadec-9-enoic acid, haematin, a sulfonamide, salicylate, sodium dodecyl sulfate, or 4,4′

-(1,1-dioxido-3H-2,1-benzoxathiole-3,3-diyl)bis(2,6-dibromophenol).

6. The system as recited in claim 1, wherein the preparation zone is further configured to combine additional agents with the fluid sample prior to the sensing zone providing electrical energy.

7. The system as recited in claim 6, wherein the additional agents include at least one of a surfactant, buffer, salt, or second release agent.

8. A system for electrochemical detection of total serum bilirubin, the system comprising:

a microfluidic cartridge comprising;

a receiving zone configured to receive a fluid sample, wherein the fluid sample comprises bilirubin bound to albumin;

a preparation zone configured to receive the fluid sample from the receiving zone and combine the fluid sample with a release agent in order to release the bound bilirubin from the albumin;

a sensing zone having multiple electrodes and configured to receive the fluid sample from the preparation zone and provide electrical energy from the electrodes to a connector; and

a device configured to receive a portion of the microfluidic cartridge, wherein the device comprises;

a receptacle configured to receive and be in electrical communication with the connector;

a controller in electrical communication with the receptacle and configured to;

control an electric potential on at least one of the electrodes; and

receive the electrical energy and provide information regarding a total serum bilirubin concentration in the fluid sample wherein the multiple electrodes are screen printed electrodes.

9. The system as recited in claim 8, wherein the fluid sample is an untreated blood sample of the subject.

10. The system as recited in claim 8, wherein the release agent is in the form of a dry solid.

11. The system as recited in claim 8, wherein the controller is further configured to provide additional information regarding the concentrations of conjugated bilirubin, unconjugated bilirubin, and albumin.

12. The system as recited in claim 8, wherein the release agent is cocamidopropyl sulfobetaine, 3[3-Cholamidopropyl)-dimethylamminonio]-1-propanesulfonate, 3-[3-Cholamidopropyl)-dimethylamminonio]-2-hydroxy-1-propanesulfonate, cocamidopropyl betaine, caffeine, sodium benzoate, sodium acetate, ethylene glycol, hexadecanoic acid, (9Z)-octadec-9-enoic acid, haematin, a sulfonamide, salicylate, sodium dodecyl sulfate, or 4,4′

-(1,1-dioxido-3H-2,1-benzoxathiole-3,3-diyl)bis(2,6-dibromophenol).

13. The system as recited in claim 8, wherein the preparation zone is further configured to combine additional agents with the fluid sample prior to the sensing zone receiving a portion of the fluid sample.

14. The system as recited in claim 13, wherein the additional agents include at least one of a surfactant, buffer, salt, or second release agent.

15. The system as recited in claim 8, wherein the device is further configured to measure a temperature of the fluid sample and maintain the temperature of the fluid sample between 20 and 40 degrees Celsius.

16. The system as recited in claim 8, wherein the preparation zone further comprises at least one filter.

17. The system as recited in claim 8, wherein the microfluidic cartridge further comprises at least one external identifier.

18. The system as recited in claim 17, wherein the external identifier provides information about the date of manufacture of the microfluidic cartridge, wherein the information about the date of manufacture is used to provide information regarding the total serum bilirubin concentration.