What laboratory assays detect SARS-CoV-2 spike protein in blood or tissues?

1. ELISA and plate‑based antigen capture — the clinical baseline

Enzyme‑linked immunosorbent assays (ELISAs) are widely used to measure antibodies to spike and to quantify recombinant spike proteins in research; published work testing Ig products used ELISA against recombinant spike and RBD to measure binding activity, showing ELISA remains a common, validated assay for spike‑related measurements in laboratory settings ^[4]. Available sources do not state routine clinical use of ELISA to measure circulating spike antigen in patient blood across healthcare systems; most ELISA references in the collection concern antibody detection or research quantitation of recombinant proteins ^[4].

2. Ultrasensitive research sensors: nanowells, plasmonics, SERS and transistor assays

Multiple recent research studies describe highly sensitive, label‑free platforms that detect spike protein directly. A nanowell impedance sensor reported a detection limit of ~0.2 ng/mL (1.5 pM) for spike protein in buffer and artificial saliva ^[2]. A plasmonic H‑shaped nano‑aperture SERS platform reported a detection limit of 0.85 ng/mL for spike, and surface‑enhanced Raman approaches have been advanced for simultaneous antigen/antibody readouts ^{[3] [1]}. Other reported transistor/multi‑antibody assays claim femtomolar‑level capture affinity for S1 domains (as low as ~0.34 fM in a cited review of methods), demonstrating that push‑model analytical platforms can reach extraordinary sensitivity in controlled conditions ^[1].

3. Electrochemical and aptamer‑based detection: rapid, reagentless options

Electrochemical aptamer‑based (EAB) sensors have been developed to provide rapid, reagentless, quantitative spike protein measurements in biological fluids; these platforms aim for single‑step testing and real‑time readouts and were explicitly designed for spike S protein detection in matrices ^[5]. The sources show continued active development of EAB and related electrochemical sensors as alternatives to antibody‑based capture, especially for point‑of‑care or high‑throughput screening ^[5].

4. What the sources say about blood vs. tissue detection and clinical translation

The assembled literature emphasizes detection of spike protein in buffers, saliva surrogates, plasma samples in small research cohorts, and recombinant protein testing rather than validated, widely deployed clinical assays for circulating spike antigen in blood or tissue biopsy specimens ^{[2] [3] [5] [1]}. Clinical serology assays cited in these sources mostly measure host antibodies that bind spike rather than measuring spike antigen itself ^[4]. Available sources do not document a broadly adopted, regulatory‑cleared blood spike antigen test for routine clinical diagnostics.

5. Interpretive context and limits: sensitivity, matrices and clinical meaning

Reported limits of detection vary widely by platform and sample matrix — from femtomolar affinity claims in transistor systems to sub‑ng/mL LODs in nanowell and SERS devices — but sensitivity in buffer or saliva surrogates does not guarantee equivalent performance in complex human plasma or tissue, where protein binding, proteolysis and matrix effects can reduce recoverable signal ^{[1] [2] [3]}. The sources note many techniques are proof‑of‑concept or research grade; they do not establish that detection equates to clinically relevant persistence of spike protein in patients’ blood or tissues ^{[1] [4]}.

6. Competing perspectives and potential agendas

Research groups and device developers emphasize analytical sensitivity and rapid detection as selling points ^{[2] [3] [5]}. Reviews and clinical serology studies underscore that antibody assays are the mainstream tool for surveillance and therapeutics assessment ^{[4] [1]}. Some narrative literature raises concerns about spike protein effects in pathophysiology and long COVID; those discussions cite cell/animal models and in vitro assays using spike subunits but do not establish standardized clinical assays for measuring spike in patients ^[6]. Readers should note that device developers have incentives to highlight low LODs in controlled settings, while clinical researchers prioritize validation, specificity and clinical correlation ^{[2] [1] [4]}.

7. Bottom line for clinicians and researchers

If you need to detect spike protein in blood or tissue for research, the sources point to ELISA, electrochemical aptamer sensors, SERS/plasmonic platforms and novel nanowell/transistor assays as available approaches with sub‑ng/mL to femtomolar analytical performance claimed in controlled studies ^{[4] [5] [3] [2] [1]}. If your goal is routine clinical diagnostics or regulatory‑grade measurement of circulating spike antigen, available sources do not document a standard, widely adopted clinical assay for that purpose and caution that matrix effects and validation remain limiting factors ^{[4] [1]}.