US-12625081-B2 - Single-use clinical spectrophotometer

Abstract

The single-use disposable spectrophotometer described in this disclosure can measure one or more blood chemistry analytes from a drop of whole blood. A passive filtration system takes whole blood and delivers plasma along with a dissolved reporter molecule to one or more spectrophotometers which can operate with narrow band optical spectrum centered on an optical detection frequency. The spectrophotometer detects the changes in absorption of the plasma as a result of a chemistry reaction to determine the concentration or activity of one or more analytes.

Inventors

• Octavian Florescu

Assignees

• IN DIAGNOSTICS, INC.

Dates

Publication Date

20260512

Application Date

20210528

Claims (18)

1. 1 . A device for measuring the concentration or activity of one or more analytes comprising: a plasma comprising the analyte; a spectrophotometer; a filter mounted on a surface, wherein the filter comprises a plasma separation membrane; the surface fluidically connecting the filter with the spectrophotometer, wherein the device is configured so the plasma can flow directly from the filter onto the surface and into the spectrophotometer; wherein the spectrophotometer comprises a plurality of wells, and wherein the device is configured so the plasma flows from the surface into the wells, and wherein the wells are configured to contain the plasma, a reporter molecule dissolved in the plasma, wherein the reporter molecule is a product or reactant to a chemical reaction, and wherein the chemical reaction is homogeneous and label-free, and wherein the chemical reaction is limited by a concentration or an activity of the analyte in the plasma in the well; and wherein the spectrophotometer is configured to measure a rate of change or absolute change of the concentration of the reporter molecule in the plasma in the well, corresponding to the concentration or the activity of the analyte in the plasma in the well.
2. 2 . The device of claim 1 , wherein the spectrophotometer comprises a light emitting diode (LED) configured to emit a light with a peak frequency at an optical detection frequency and with a narrow band optical spectrum, wherein the LED is configured so the light traverses through the plasma, and wherein the reporter molecule absorbs part or all of the light traversing through the plasma.
3. 3 . The device of claim 2 , wherein the spectrophotometer comprises a photodetector, wherein the device is configured so the light is incident on the photodetector and wherein the photodetector is configured to be sensitive to the light at the optical detection frequency.
4. 4 . The device of claim 3 , wherein the spectrophotometer comprises a reflector configured to redirect the light at the optical detection frequency through the plasma in the well.
5. 5 . The device of claim 4 , wherein the reflector comprises a protrusion, and wherein the protrusion contacts the plasma in the well.
6. 6 . The device of claim 5 , wherein a nominal path length can vary from an actual path length by less than 5%.
7. 7 . The device of claim 4 , wherein the spectrophotometer comprises a surface capillary, and wherein at least the edge of the filter is partially or completely inside the surface capillary.
8. 8 . The device of claim 4 , wherein an array of wells (AOW) comprises the plurality of wells, and wherein a gap between the filter and the AOW is less than 2 mm.
9. 9 . The device of claim 4 , wherein the spectrophotometer comprises an integrated circuit (IC), and wherein the photodetector is integrated in the IC.
10. 10 . The device of claim 9 , wherein the surface is co-planar with a surface of the IC.
11. 11 . The device of claim 4 , further comprising a prefilter above or adjacent to the filter, and wherein the prefilter is coated and/or impregnated with prefilter reagents.
12. 12 . The device of claim 11 , wherein the analyte comprises at least one of alanine aminotransferase (ALT), aspartate aminotransferase (AST), potassium, magnesium, glucose, creatine kinase, total cholesterol or blood urea nitrogen.
13. 13 . The device of claim 4 , wherein the LED is configured to emit the light at a wavelength of 340 nm, wherein the narrow band optical spectrum of the light has a Full Width Half Maximum (FWHM) of less than 20 nm, and wherein the reporter molecule comprises nicotinamide adenine dinucleotide (NADH).
14. 14 . The device of claim 4 , further comprising a near-field communication (NFC) wireless module configured to wirelessly transmit measurement results from the device to a nearby wireless device.
15. 15 . The device of claim 4 , further comprising a battery electrically connected to the spectrophotometer, wherein the battery is configured to supply power to the spectrophotometer.
16. 16 . The device of claim 4 , further comprising an additional magnetic sensing IC configured to perform magnetic particle labeled immuno-assays.
17. 17 . The device of claim 4 , wherein the LED is configured to emit the light at a wavelength of 405 nm, wherein the narrow band optical spectrum of the light has a FWHM of less than 20 nm.
18. 18 . The device of claim 17 , wherein the analyte comprises at least one of alkaline phosphatase (ALP), amylase, calcium or gamma glutamyltransferase.

Description

CROSS-REFERENCE TO RELATED APPLICATION This application is a continuation-in-part of International Application No. PCT/US19/63877, filed Nov. 29, 2019, which claims priority to U.S. Provisional Application Nos. 62/772,778, filed Nov. 29, 2018; 62/817,706, filed Mar. 12, 2019; and 62/858,865, filed Jun. 7, 2019, all of which are incorporated by reference in their entireties. TECHNICAL FIELD The present disclosure relates to single-use, disposable, digital biosensors and integrated circuit-based biosensors with whole blood sample preparation BACKGROUND A chemistry test can be used to measure the concentration or activity of one or more analytes, i.e., endogenous compounds, circulating in blood. These analytes are often small molecules such as ions, blood gases and enzymes. Examples of analytes include albumin, blood urea nitrogen, uric acid, calcium, carbon dioxide (bicarbonate), chloride, creatinine, glucose, potassium, sodium, magnesium, phosphorus, lactate, amylase, lactate dehydrogenase, direct bilirubin, total cholesterol, high-density lipoprotein cholesterol, triglycerides, total bilirubin, total protein, creatine kinase, alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST) and gamma glutamyltransferase. These chemistry tests are also commonly referred to as blood chemistries, general chemistries, basic or complete metabolic panels, chemistry panels or specific organ panels. The results from a chemistry test can provide insight into the function of the kidneys, liver, heart, pancreas, bones and lungs among other biological systems. The results from a chemistry test can be critically time sensitive, yet the instruments capable of performing such measurements are often relegated to emergency departments and central laboratories and require burdensome calibration and maintenance. Spectrophotometry was developed by Arnold Beckman in 1940. While the testing modality for a variety of blood tests has evolved, spectrophotometry continues to be the bedrock of modem laboratory testing. This disclosure miniaturizes and integrates a spectrophotometer into a single-used disposable device. Users can place a samples of blood from a finger-stick or venipuncture on the inlet of device. The sample is wicked into a membrane filtration sample preparation system, which passively provides plasma to a disposable spectrophotometer for quantification of one or more analytes in the sample. Spectrophotometer 15 can differ from conventional spectrophotometers in a variety of ways: 1) the detection in this disclosure can be performed on undiluted samples, 2) the path length can be much shorter than in conventional spectrophotometers, 3) the illumination can be from an LED 5 emitting light with a narrow band optical spectrum, 4) the reflector 6 can be made from injection molded plastic, 5) the reagents can be stored in a dry state in device and 6) there can be at least one photodiode per well, 7) Spectrophotometer in this disclosure can be integrated into a single-use disposable. SUMMARY Device is a single-use clinical spectrophotometer for measuring the concentration or activity of one or more analytes 36 in plasma 17. Device can comprise: A battery 40 that can be electrically connected to a spectrophotometer 15, wherein battery 40 can supply power to spectrophotometer 15;A digital display 41 that can be electrically connected to spectrophotometer 15, wherein digital display 40 can display the concentration of one or more analytes in plasma 17; A filter 2 that can be mounted on surface 11, wherein filter 2 can be a plasma separation membrane, and wherein filter 2 can be impregnated with a reporter molecule.A surface 11 that can fluidically connect filter 2 with spectrophotometer 15, wherein plasma 17 from filter 2 can flow directly from surface 11 into spectrophotometer 15;A chemical reaction 35 that can be a homogenous reaction limited by the concentration or activity of analyte 36 in plasma 17 in well 19, and wherein reporter molecule can be a product or reactant to chemical reaction 35,A spectrophotometer 15 that can contain plasma 17 with dissolved reporter molecule in suspension, wherein spectrophotometer 15 can measure the rate of change or absolute change of the concentration of the reporter molecule in plasma 17 in well 19, and calculate a corresponding concentration or activity of analyte 36 in plasma 17 in well 19. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1A presents a cross sectional side view of device that can have a filter 2, a surface 11 and a spectrophotometer 15. FIG. 1B is a cross sectional top view of IC 9 and LED 5 mounted on PCB 3. FIG. 1C presents a cross sectional top view of tape 10 with channels 23 and 25 mounted on PCB3. FIG. 1D shows a cross sectional top view of filter 2, filter 55 and AOW 4 mounted on tape 10. FIG. 1E is the top view of device with reflector 6. FIG. 2 presents a cross sectional side view of device with IC9 and filter 2 mounted above AOW 4. FIG. 3 is